Refinement of Subnetwork Discovery Algorithm for Biological Networks

REFINEMENT OF SUBNETWORK DISCOVERY ALGORITHM FOR BIOLOGICAL NETWORKS

SATRIA PUTRA SAJUTHI

A Thesis Submitted to the Graduate Faculty of

WAKE FOREST UNIVERSITY

in Partial Fulllment of the Requirements

for the Degree of

MASTER OF SCIENCE

in the Department of Computer Science

May, 2010

Winston-Salem, North Carolina

Approved By:

Jacquelyn Su Fetrow, Ph.D., Advisor

Examining Committee:

Victor Paúl Pauca, Ph.D., Chairperson William Hansel Turkett Jr., Ph.D. Table of Contents

Acknowledgments ...... iv

List of Figures...... v

List of Tables...... vi

Abstract ...... vii

Introduction...... 1

Chapter 1 Background...... 4 1.1 JActiveModules (JAM) ...... 8 1.2 JActiveModules Algorithm ...... 9 1.3 Problems with Current JActiveModules ...... 12 1.3.1 Initial List of Subnetworks ...... 12 1.3.2 Unbounded List of Subnetworks ...... 13 1.3.3 Regional Scoring ...... 13

Chapter 2 Methods ...... 15 2.1 Randomize Initial List of Tracked Subnetworks ...... 15 2.2 Constrained Size of the List of Tracked Subnetworks ...... 16 2.3 Modication to Improve Regional-Scoring Heuristic ...... 17 2.4 Running JAM over Multiple Trials ...... 18 2.5 Sensitivity and Specicity ...... 21

Chapter 3 Method Validation...... 23 3.1 Networks ...... 23 3.2 Validation for randomizing initial list of subnetworks ...... 25 3.3 Validation for Limiting the Size of the Subnetwork List ...... 29 3.4 Validation for Improved Regional Scoring ...... 33 3.5 Modied JAM Result with All Modications Active ...... 35

Chapter 4 Biological Results : Identication of Active Subnetworks from Time Course Microarray Data ...... 37 4.1 Datasets Description ...... 37 4.1.1 Mouse KEGG Network ...... 37 4.1.2 Dendritic Cell Microarray Data ...... 38

ii iii

4.2 Conversion from Signal Log Ratio to p-value ...... 38 4.3 Conversion from Ay Id to Entrez ID ...... 39 4.4 Overall Process ...... 41 4.5 From Subnetworks to Pathway Annotation ...... 44

Chapter 5 Conclusion and Future Work...... 50 5.1 Conclusion ...... 50 5.1.1 Comparison to other methods ...... 51 5.2 Future Work ...... 53

Appendix A Subnetwork Results ...... 59

Appendix B Expression Data for Test Networks ...... 79

Appendix C Expression Data and Annotations for KEGG Network ...... 91 Acknowledgments

First, I want to extend my gratitude to my advisor, Dr. Jacquelyn S. Fetrow, who introduced the eld of bioinformatic and system biology to me and guided me in every step of my thesis work. I always appreciate the 8 o'clock session in the Dean's oce. I also want to thank Dr. William H. Turkett who always been patient and open when I need a brainstorm. His numerous advices help me a lot during the construction of my writing and enabling my mind to think critically. Also, I would like to thank Dr. V. Paul Pauca for his help and input during the initial phase of my thesis and for his willingness for being my thesis committee member.

I also want to thank my academic advisor, Dr. David John, who always keep track of my academic progression throughout the years. I want to thank Stacy Howerton for being a good friend and Amy Olex who helped to guide me when Jacque is busy with her dean's work. I also like to say thank to Paul Whitener for lend me the Sunray which has been useful to my thesis work. The friendship from Shuai and Harry also contribute a lot when I need friends to have fun and escape from the stress of the thesis work.

I would like to thank my aunt for a place to live in the past two years. She also help me adapts to a way of living in the United States. Finally, I would like to thank my parents for enormous supports. They always believe in me and support my decision to continue my study to another ve years of graduate school.

iv List of Figures

1.1 JAM algorithm behaviour when exploring state space ...... 10 1.2 The regional-scoring heuristic takes into account all of the surrounding neighbors when scoring a subnetwork ...... 12

2.1 An example of the distribution of nodes resulting from a JAM search over ten runs shows inconsistency in the subnetwork results ...... 19

3.1 Various networks used for validation purposes ...... 24 3.2 Randomizing the initial list of subnetworks neither improves overall scores nor prevents unusually low scores ...... 25 3.3 The progression of size-distribution from original JAM ...... 26 3.4 Graphs of the iteration space of modied JAM runs in term of size distribution and score distribution that lead to high-scoring subnetworks and low-scoring subnetworks, show a relationship between size and score ...... 28 3.5 Top score distribution from original JAM (green) shows consistently higher Z-scores than Z-scores from modied JAM (red) over one hundred JAM runs 29 3.6 Tracing the iteration space of size and score distribution demonstrates how the size of the list of tracked subnetworks aects the performance of the search 30 3.7 Examples of the state of active nodes achieved for the mouse cell cycle network as a result of employing the original JAM algorithm and the JAM algorithm with only the modication to limit the size of the tracked subnetwork list . . 32 3.8 The subnetwork result from modied JAM with improved regional scoring (red bordered) shows better connectivity compared to the result from the original JAM (dashed orange border) on the tadpole network ...... 34 3.9 The modied JAM results oer an increase in sensitivity and decrease in specicity compared to original JAM results over ten runs on galactose utilization pathway ...... 35

4.1 An example of conversion from Ay ID to Entrez ID ...... 41 4.2 Proposed JAM search with DC data and KEGG network as an input . . . . 43 4.3 Genes labeled as TLR signaling pathway across timepoint ...... 48 4.4 Dynamic of gene activity in toll-like receptor signaling pathway ...... 49

v List of Tables

2.1 Example of binomial distribution over 10 JAM runs with p : 624/2691. . . . 21

3.1 Subnetworks distribution over 100 runs ...... 34

4.1 1hr DAVID annotation result...... 46 4.2 3hr DAVID annotation result ...... 46 4.3 6hr DAVID annotation result ...... 46 4.4 12hr DAVID annotation result ...... 46 4.5 24hr DAVID annotation result ...... 47 4.6 Summary of the results from Table 4.1-4.5 ...... 47

vi Abstract

The abundance of biological experimental data from new high-throughput technologies, such as microarray data, suggests the need for new methods to study biological processes using a systems-based approach. Handling this huge volume of data requires the development of new computational methods to analyze and extract interesting pieces of biological information.

JAM (jActiveModules) is a Cytoscape plugin developed to nd connected sets of genes with high levels of dierential expression. This network approach helps biologists to generate new hypotheses concerning the biological mechanisms underlying observed changes in gene expression.

In this work, the search algorithm of JAM is modied and measured. The goal was to improve the sensitivity and specicity of the method compared to the original JAM algorithm. The modications made to the search algorithm involve: randomizing the starting point of the search, constraining the number of subnetworks maintained while searching, and improving the regional-scoring heuristic. Importantly, these modications increase the number of signicant genes observed in the results. To ensure consistency in the search results, we apply the search algorithm multiple times and develop a statistical lter to retain consistent genes appearing across JAM runs. Furthermore, we apply this improved version of JAM to DC (Dendritic Cell) maturation microarray data and KEGG pathways to study the underlying mechanisms behind the DC maturation process, an essential part of the development of protective immunity to a number of infectious pathogens.

vii 1

Introduction

The advancement of high-throughput technology such as microarray is capable to generate large amount of gene expressions data. In particular, this technology allows researcher to study the eects of an external stimulus, such as drug or virus, on system wide gene expression. The large volume of data generated by microarray experiments have given rise to new computational methods to analyze and understand the data.

In the eld of molecular biology, genes usually work together with other genes. This collaboration between genes is required to perform various important functions inside the cell. Many of these interactions between genes or gene products have been studied and doc- umented in various public databases. The rapid growth of interaction data resources allows researcher to analyze gene expression data within a network context, where the network is dened by the known interaction data.

The idea to integrate interaction data and gene expression data was rst presented by Ideker et. al. in 2002. In that work, a network was constructed with genes or gene products as the nodes, known interactions as edges, and weights attached to the nodes based on the expression value of the associated genes. A method was proposed to nd an active subnetwork within the network, where an active subnetwork is dened by a connected region in the network that consists of nodes with signicant changes of expression. Ideker's work presented both a subnetwork scoring scheme and an optimization algorithm based on simulated annealing approach. The method itself was implemented in a Cytoscape plugin called jActiveModules. The algorithm's intention is to maximize the score of the subnetwork by heuristic search through the subnetworks space. However, there are several problems with implementation of jActiveModules that are believed to lessen the performance of the originally developed search algorithm.

In this thesis work, three modications have been employed to address the perceived problems of the current jActiveModules implementation. The rst modication is random- ization of the initial list of subnetworks used to start the search. The motivation behind this modication is to ensure additional randomness and to support exploration of a wider area 2 of the subnetworks space. The second modication is limiting the size of the list of tracked subnetworks during the search. This modication is important in cases where a network contains a majority of low scoring nodes. In such cases, the size of tracked subnetworks list will grow without constraint and can trap the search in the sea of low-scoring subnetwork. The third modication is the improvement of regional-scoring heuristic. This modication allows the search to look one neighbor away from the tracked subnetworks to selectively discover neighbors that allow for score improvements.

An additional issue that was found with jActiveModules was inconsistency across multiple runs of the algorithm. This inconsistency is mostly encountered when the algorithm is applied to large networks. To address this inconsistency problem, a statistical process was developed that determines the probability of a node being included in k or more subnetworks outputs from n jActiveModules runs. These binomial-based probabilities can be used to conclude how many times a node must show up in the results of multiple jActiveModules runs to be considered signicant. The results from employing this ltering process are more consistent subnetworks across multiple runs.

Furthermore, this modied jActiveModules is used to search for active subnetworks in a biological network derived from KEGG overlaid with time course gene expression data from a dendritic cell (DC) microarray experiment, with the intention of understanding the biology underlying the maturation process of dendritic cell after infection. In the microarray experiment, dendritic cells are stimulated with poly:IC (to mimic viral infection) and the gene expressions across the genome (using an Aymetrix chip) are measured at ve time points (1hr, 3hr, 6hr, 12hr, and 24hr). The experiment is intended to investigate the biology underlying the maturation process of dendritic cell after it had been infected. The subnetwork results from the application of modied jActiveModules to this microarray data within the context of KEGG network reveal some biologically interesting pathways to be involved in the DC maturation process, such as arachidonic acid metabolism. The result also highlight pathways already known to be involved in the DC maturation process, such as Toll Like Receptor (TLR) signaling pathway and JAK-STAT signaling pathway. 3

This thesis is organized as follows : Chapter 1 provides an overview description of the subnetwork searching problem and introduction of a tool called jActiveModules to address this searching problem. This chapter also describes the potential problems within JAM based on its current implementation of the search algorithm. Chapter 2 details the methods used to address the problems described in chapter 1. Chapter 3 describes the results from validating the modications made to the original JAM algorithm, on various test networks. Chapter 4 provides an overview of the process of and the results from applying the modied version of JAM to the dendritic cell microarray data. Finally, Chapter 5 describes the conclusion drawn from the work and the suggested future work from this thesis. Chapter 1: Background

Gene expression is the general term for the biological process through which DNA is transcribed into messenger RNA (mRNA), which is then translated into proteins, the key functional units of the cell. Gene expression is a complex and tightly regulated process that allows a cell to respond dynamically to external stimuli and adapt to localized cellular needs. Generally, genes and their product proteins act together in a cooperative manner to perform a certain cellular function. Proteins can interact with other proteins, DNA, RNA or other small molecules to form complexes and pathways that consitute the molecular machinery of living organisms.

While gene expression has historically been studied for a small number of genes at a time, recent advances in technology are allowing scientists to study gene expression data in a more global context. One of the most important new technologies, microarrays (Schena et al., 1995), allows scientists to study thousands of genes simultaneously, enabling whole genome coverage of some organisms. This technology is based on the complementary nature of DNA and RNA. Microarray chips consist of thousand of spots with a piece of DNA embedded at each spot. These DNA fragments are called probes as they are used to investigate the activity of the genes. An mRNA molecule which is complementary to the gene in the probe should hybridize to the probe, forming a bond of mRNA-DNA. These mRNA molecules have been labeled with a ourescent material. The amount of hybridization will be indicated by the brightness of the material in mRNA, which in turn provides the measure of the level of mRNA for a gene.

Generally, there are two dierent types of microarray : cDNA (complementary DNA) microarray (Lennon and Lehrach, 1991) and oligonucleotides microarray (Southern et al., 1994). The dierence lies in the DNA fragments occupying the spot positions in the microarray. In a cDNA microarray, a large fragment of DNA representing a gene is embedded into multiple

4 5 spots in the microarray. In an oligonucleotide microarray, the spots on a microarray chip contain single stranded DNA oligonucleotides usually around 20 nucleotides long. Instead of having one probe set of cDNA per gene, an oligonucleotide microarray contains two sets of probe pairs for each gene. One set is called the 'perfect match' oligonucleotide, while the other sets contains 'mismatch' oligonucleotides that are identical to the 'perfect match' set except for just one nucleotide in the middle of the sequence. The purpose of the mismatch probe is to measure the amount of cross-hybridization that occurs. The other dierence between these two types of microarray lies in the experimental design. With a cDNA microarray, two dierent samples labeled dierently, control and case, are mixed together and then hybridized to the microarray chip. This design gives the relative dierence between gene expression in control and case in one chip. With an oligonucleotide microarray, only one mRNA sample is extracted and hybridized onto the chip. In this experimental design, comparison between control and case requires two chips.

Two typical styles of microarray experiments are time-series and multiple perturbation microarray experiments. Time-series experiments usually show the progression of gene expression activity in the cell after a certain stimulation has been applied. Multiple perturbation experiments usually target a specic gene and knock out that gene, then observe the dierence in expression across thousands of genes under this condition as compared to wild type (the native strain).

The problems of dealing with large amounts of gene expression data have given rise to new analytical methods and tools to extract biologically-relevant information from such data. Clustering was one of the early approaches designed to address this problem. One example application of clustering analysis is to discover group of genes that have similar expression pattern (coexpressed genes). Such groups of related genes have been predicted to contains genes that are part of the same pathway or to be controlled by the same transcriptional regulator (co-regulated) (Allocco et al., 2004). Multiple variants of clustering algorithms such as hierarchical clustering (Eisen et al., 1998), k-means (Tavazoie et al., 1999), and fuzzy c-means (Dembélé and Kastner, 2003) have been implemented and applied in attempts to 6

nd patterns of gene expression from the time-series or multiple perturbation microarray experiments. Each of these algorithms require a measure of similarity between entities. Various measures such as Euclidean distance (Smet et al., 2002; Tavazoie et al., 1999) and Pearson correlation (Tang and Zhang, 2002), have been used previously.

Genes/gene products interact with each other in a complex network. These interactions enable the cell to perform dierent functions. Identication of the network is important to understand the biological mechanisms that regulate the cell. In order to understand the interaction between genes, a whole picture of gene activity in the cell is needed under a specic condition and at a given time. Researchers have used microarray data in attempts to reverse engineer biological networks from temporal or conditional gene expression proles. These modeling approaches try to predict the relationship between genes/gene products by using mathematical modeling based on the expression values of each gene over multiple conditions or timepoints. Several network inference approaches based on Bayesian networks (Dojer et al., 2006), information-theory approaches (Butte and Kohane, 2000), and ordinary dierential equations (Yeung et al., 2002) are popular in this domain. Many of these approaches require the data to be discretized instead of being in its raw continuous form as read o of the microarray chip.

Along with gene expression data, new high throughput technologies have allowed for the measurement and accumulation of large amounts of biological entity interaction data, such as protein-protein interaction data (Rual et al., 2005) and DNA-protein interaction data (Ren et al., 2000). These high throughput data, along with other interaction data extracted from the biological literature, are stored in a number of public interaction databases. In addition to the two types of protein interaction data described above, many interaction databases store information on signal transduction, metabolic, and transcriptional regulatory interactions and networks. A signal transduction network is often triggered by a ligand binding to a receptor, initiating a cascade of protein transformations that lead to a specic cellular response. A metabolic network is a series of enzymatic reactions that convert one metabolite to another metabolite to be used or stored inside the cell. A transcriptional 7

regulatory network captures the interaction between a transcription factor (a protein that controls transcription by binding to a specic DNA region) and its targets. Databases such as KEGG (Kanehisa and Goto, 2000), BioGrid (Stark et al., 2006), BIND (Alfarano et al., 2005), and IntAct (Hermjakob et al., 2004) have been established as interaction data repositories.

Recently, researchers have begun to explore gene expression data within the context of the interaction data available in these databases, data which essentially constitutes components of known biological networks. One such network-based approach is to identify gene modules associated to phenotypes, diseases or changing conditions based on a particular perturbation applied to the cell. A method to search for such gene modules was rst proposed by Ideker and coworkers (Ideker et al., 2002). The gene modules of interest in this work were termed active modules/subnetworks/pathways, which can be loosely dened as a connected set of genes in a biomolecular network which alter their responses given a specic perturbation applied to the cell. The popularity of this network based approach has been indicated by the development and implementation of various similar approaches to identify gene modules. An altenative approach to search for active subnetwork has been suggested by Rajagopalan et. al. who developed a new scoring scheme and a new heuristic to search for active subnetworks of smaller and interpretable size (Rajagopalan and Agarwal, 2005). Other approach from Dittrich et. al. address the possibility to look for exact solution for the subnetwork searching problem based on ILP (Integer Linear Programming) formulation (Dittrich et al., 2008). Other researchers look for connected set of genes that have similar expression pattern. Ulitsky et. al. have been developed a method to search for coexpressed genes that are also connected in the network based on gene expression and certain clinical parameter (Ulitsky and Shamir, 2008). Guo et. al. have been developed a method to search for subnetwork of coexpressed genes using an edge based scoring approach (Guo et al., 2007).

The method for nding active subnetworks originally described in the 2002 paper (Ideker et al., 2002) has been implemented as a Cytoscape plugin called jActiveModules (JAM). Cytoscape (Shannon et al., 2003) is a well known tool for visualizing biological networks and 8

integrating these networks with gene expression proles and other annotations. JAM was chosen as the basis for this work because it is a popular method, based on a survey of the current literature. There are several examples where JAM has been applied to extract active subnetworks from Drosophila (Bauer et al., 2008), yeast (Stuart et al., 2009), and C. elegans interaction data (Meyer et al., 2007).

1.1 JActiveModules (JAM)

An active subnetwork is a connected subgraph that shows signicant change of expression over certain perturbation. In other words, it detects groups of dierentially expressed genes along the pathways aected by external stimulation. JAM requires an input of a known biological network and a value for each node/gene indicating the signicance of expression change (p-values). The biological network mentioned can be as simple as a protein-protein interaction network or as complex as signaling and metabolic pathways.

There are two main problems that JAM tries to solve to nd active subnetworks. The rst problem is how to adequately score an active subnetwork, while the second problem is how to nd the best scoring subnetwork from a given network.

In order to rate the biological activity of a particular subnetwork, JAM uses a scoring method based on p-values. First, JAM converts the p-values for each gene into z-scores using the inverse normal CDF (Cumulative Density Function) with smaller p-values corresponding to high z-scores. Then, to produce the aggregate score for an entire subnetwork A of k genes, it uses the following formula:

1 X ZA = √ Zi , where Zi is the ZScore of node i in the subnetwork (1.1) k iA The best scoring subnetwork problem is also known as Maximum Weight Connected Sub- graph (MWCS) (Dittrich et al., 2008). This problem has been proven to be NP-hard for weighted vertices, where vertices can have either a positive or a negative weight. The proof can be found in the supplementary materials of (Ideker et al., 2002). As an approximation 9 for this problem, Ideker and coworkers proposed a search algorithm based on simulated annealing (Ideker et al., 2002), a class of well known algorithms employed to solve optimization problems (Kirkpatrick et al., 1983).

1.2 JActiveModules Algorithm

Algorithm 1 Simulated Annealing Algorithm Input : A graph G = (V,E,Wv) which is a vertex-weighted network of molecular interactions, a number N of iterations, a number of output subnetworks M, and a temperature function Ti which decreases geometrically from Tstart to Tend Output : subgraphs Gw of G (1) Initialize Gw by setting each vV to active with probability ½ and S0 as the score of Gw (2) FOR i = 1 to N DO (3) Randomly pick a node v and toggle its state; (4) Compute the score si for the working subgraph Gw (5) IF (si>si−1) keep v toggled; (6) ELSE keep v toggled with probability p = e(si−si−1)/Ti (7) Output Gw

The JActiveModules search algorithm starts with initialization of user dened parameters such as network G, starting temperature Tstart, end temperature Tend, number of iterations N, and the number of output subnetworks M. In initialization of this algorithm, each node in G will be randomly toggled active (on) or inactive (o). A group of active nodes will create a subnetwork if there is a path between each member of the group. Gw denotes the list of subnetworks of G induced by the active nodes. After the initialization phase, the algorithm will iterate through the state space of subnetworks, dependent on the number of iterations mentioned earlier. For each step of the iteration, the algorithm will randomly pick one node and toggle that node active or inactive depending on the previous state of the node. The result of toggling nodes active or inactive will be one of the three actions illustrated in Figure 1.1 :

• Removing a subnetwork of only one node from Gw. (Case 1) 10

• Joining two or more subnetworks together into one subnetwork. (Case 2)

• Making one subnetwork break into two or more subnetworks. (Case 3)

(a) Initial Gw (b) Case 1

Figure 1.1: JAM algorithm behaviour when exploring state space. Solid circles represent active nodes, dashed circles represent inactive nodes. The node pointed to by the red arrow represents a node being toggled on/o with respect to the previous subgure.

In each iteration, the algorithm will either move to a new Gw or keep the current Gw. This decision to move to the proposed new state is based on the dierence between the previous score and the new score. If the new score is higher than the previous score, the algorithm will move to the new state. Otherwise, a switch to the new Gw is made dependent on a probability that is calculated based on the delta of the score of the current Gw and the proposed Gw and the current temperature. The higher the current temperature and the lower the delta, the higher the chance the algorithm will move to a proposed Gw with a poorer score. The reason for accepting a state with a worse score is to give the algorithm the chance to escape from a local maximum.

As indicated in their work (Ideker et al., 2002), Ideker and colleagues employed two modications to the simulated annealing algorithm, suggesting these would improve the al- 11

gorithm's search performance. First, they maintain multiple subnetworks simultaneously when doing search. This is done because they believe there are multiple high scoring subnetworks in the graph. Moreover, maintaining multiple subnetworks increases the eciency of annealing because it will increase the chance to merge several low-scoring subnetworks into a single high-scoring subnetwork.

Second, they introduced a heuristic called hub-nding. This method is meant to address a problem in networks with many hubs (high degree nodes). Since a hub is highly connected, adding a hub to the subnetwork will immediately add other active nodes adjacent to the hub. Therefore, if the surrounding area around the hub is active and has a low score, the new subnetwork created will have a low score regardless of the contribution of the hub node. The hub-nding heuristic works by checking a node being added at each iteration of the search. If that node has a degree greater than a user-denable parameter, JAM will toggle o all neighbors of that node that are not in the current top-scoring subnetwork.

Furthermore, Ideker and coworkers tried to improve hub-nding by introducing another heuristic called regional scoring. In regional scoring, the search is restricted to only score the region of a subnetwork. The region is dened by the subnetwork created by active nodes (core) and inactive nodes one neighbor away surrounding the subnetwork (neighborhood). The advantage of this approach is to help the search to potentially grow a subnetwork with a low-scoring core if it has a high-scoring neighborhood. Another advantage of using regional scoring is it reduces the search space by forcing the subnetwork to be scored by region. For instance, in a complete network with three nodes connected to each other, traditional annealing might nd all seven1 combination of subnetworks as illustrated in Figure 1.2b. In contrast, regional scoring will only see these nodes as a single region.

1The number of possible subgraphs from complete graph: 2n − 1,where n is the number of vertices 12

(a) (b)

Figure 1.2: The regional-scoring heuristic takes into account all of the surrounding neighbors when scoring a subnetwork. This behaviour reduces the number of potential subnetworks to observe. The denition of regional scoring is illustrated in Figure (1.2a). Yellow nodes represent core and green nodes represent neighborhood. The possible subgraphs visited by traditional simulated annealing given a complete three-node network are shown in the graph in Figure (1.2b). JAM searching reinforced with regional-scoring will only visit the rst three-node subgraph.

1.3 Problems with Current JActiveModules

While the ideas proposed in the original paper will potentially give subnetworks of interest, the current implementation of that concept hinders that potential in several cases. The problems with the current JAM implementation are rooted in a lack of consistency between concept written in the original paper and implementation of the concept. In this work, the current JAM implementation refers to JAM version 2.23. This subsection will describe several parts of the current JAM implementation that are not consistent with the ideas proposed in the JAM paper and which can reduce the eectiveness of the search.

1.3.1 Initial List of Subnetworks

Simulated annealing is a stochastic algorithm that depends on randomness to solve an optimization problem. Since many local optima may exist and a global optima is not guaranteed, it is a common practice to run simulated annealing multiple times from dierent starting points to observe the convergence of the results. Although line 1 of Algorithm 1 shows that 13 an initial list of subnetworks will be chosen randomly by toggling each node active/inactive with probability of 1 , the actual implementation of that line does not implement the stated 2 behaviour. Instead of starting randomly, JAM always starts with all nodes active.

1.3.2 Unbounded List of Subnetworks

JAM keeps track of a list of highest-scoring subnetworks while searching the state space to improve the eciency of the search. By maintaining the list, JAM identies several local optima and, by keeping multiple subnetworks active, will increase the odds of several low-scoring subnetworks merging into a single high-scoring subnetwork. The number of subnetworks that one wants to keep track of is open for investigation.

Currently, the implementation of JAM does not set the upper bound of how many subnetworks to track. This unbounded property allows the list of subnetworks to grow and to include a great deal of very low-scoring subnetworks. Near the end of the iterations with many low scoring subnetworks, toggling a node to active is likely to bring several low scoring subnetworks together into a subnetwork with a worse score, which was not the original intention. When this condition is combined with the low temperature near the end of a run, it is more likely the proposed subnetwork will get rejected and the search will end up trapped in the sea of low-scoring components such that subnetworks can not grow any larger. This particular case is more likely to happen if the number of high-scoring nodes is much smaller than the number of subnetworks maintained in the list.

1.3.3 Regional Scoring

In the original implementation of JAM, a region is dened by the core and neighborhood (rst neighbors) of the core. As a result, this denition will allow the following four types of regions:

1. Region with high-scoring core and high-scoring neighborhood

2. Region with high-scoring core and low-scoring neighborhood 14

3. Region with low-scoring core and high-scoring neighborhood

4. Region with low-scoring core and low-scoring neighborhood

Given a region, JAM will make one of two choices regarding that region: add the region to the current active subnetworks list or keep it outside the list. With the current implementation of JAM, the rst type of region will denitely enter the list. The second type of region will likely be kept outside the list if the neighborhood scores very low. The third type of region might enter the list if there is a signicant score improvement in the neighborhood. The last type will not join the list except if there is no good region at all in the entire network. A problem with the current implementation of JAM lies in the second case. In that case, it is likely that a region with a high scoring core will be kept o the list, even though that core, because of its high score, may constitute part of a real subnetwork of biological interest. Chapter 2: Methods

In this work, the search algorithm of JAM is modied and the performance of the resulting algorithm is compared against that of the original. The goal was to improve the accuracy of the search method. The improvements made to the search algorithm were based on the problems outlined in Section 1.3, which involve: randomizing the starting point of the search, constraining the number of subnetworks maintained while searching, and improving the regional-scoring heuristic. Along with those three improvements, a statistical lter was developed to select subnetworks based on consistency of the results over multiple runs. Finally, sensitivity and specicity metric will be used to measure the performance of the modied algorithm.

2.1 Randomize Initial List of Tracked Subnetworks

JAM employs a simulated annealing algorithm as the method to optimize resulting extracted subnetwork scores. Because of the stochastic nature of this algorithm, it is important that the algorithm be able to widely sample the subnetwork space early on during the search process. The approach taken by the current JAM implementation, described in Section 1.3.1 always starts the search from the network with all nodes toggled on. It is believed that having additional randomness in the subnetwork space can improve the search. Based on this reasoning, the appropriate change is made so that the implementation of JAM follows the originally proposed search algorithm, where nodes are toggled on and o at random at the start of the search.

15 16

2.2 Constrained Size of the List of Tracked Subnetworks

This second modication attempts to resolve the problem in which JAM tracks more subnetworks than it should. The details of this problem were presented in Section 1.3.2. To tackle this problem, a straightforward modication was proposed to the original algorithm of JAM as illustrated in Algorithm 2. At the end of each iteration, modied JAM will check

for the size of the list of tracked subnetworks (Gw). If the size of Gw is greater than user denable parameter M, then the algorithm will prune the list to the desired size M and will toggle o all the nodes which are part of the pruned subnetworks. The ideal size for M is still open for investigation, though in this work the M is chosen to be small to focus on the most interesting networks. This issue is discussed further in the Future Work section of this thesis. JAM maintains the tracked subnetworks list in a sorted manner with high-scoring subnetworks in the lower indices and low-scoring subnetworks in the higher indices. Hence, this modication prunes the low-scoring subnetworks rst and maintains the high-scoring subnetworks. 17

Algorithm 2 Limit Gw Input : A graph G = (V,E,Wv) which is a vertex-weighted network of molecular interactions, a number N of iterations, a temperature function Ti which decreases geometrically from Tstart to Tend, and a number of tracked subnetworks M Output : subgraphs Gw of G (1) Initialize Gw by setting each vV to active with probability ½ and S0 as the score of Gw (2) FOR i = 1 to N DO (3) Randomly pick a node v and toggle its state;

(4) Compute the score si for the working subgraph Gw (5) IF (si > si−1) keep v toggled; (6) ELSE keep v toggled with probability p = e(si−si−1)/Ti (7) Sort Gw based on decreasing score

//modification start

(7) IF (size(Gw) > M) (8) FOR j = size(Gw) down to M + 1 (9) remove Gw[j] from Gw (10) toggle off all nodes in Gw[j] //modification end

(11) Output Gw

2.3 Modication to Improve Regional-Scoring Heuristic

Two problems exist when scoring a network as a `region' : a high-scoring core with a low- scoring neighborhood and a low-scoring core with a high-scoring neighborhood. The original regional scoring approach solves the second problem but not the rst one. By the denition of a region, instead of just scoring the nodes within the subnetwork, the rst neighbors of the subnetwork are also included. This behavior increases the likelihood of a low scoring subnetwork to grow if it has a high-scoring neighborhood. The goal for the following proposed method is to solve the rst problem while still maintaining the ability to solve the second problem.

In this work, an improved version of regional scoring is developed (Algorithm 3). This function is developed to replace the original regional-scoring function that will be applied 18 when scores the subnetwork. The modication lies in the modied denition of the region. In original regional-scoring, a region is dened by the core and the rst neighbors of the core (neighborhood). The denition of a region in the proposed improved version of regional scoring is the core and the rst neighbors of the core which contribute positively to the score of the region when included. The modied algorithm starts by sorting the neighborhood by score from high to low. It then iteratively add one neighbor at a time to the core, making a new component, then computes the score of the new component. If there is a score improvement by bringing the additional neighbor to the core, then keep the neighbor, else remove the neighbor and exit from the iteration.

In the case where there is no improvement made by adding neighbors to the core, a region would be scored only by the contribution from the core. This new scoring scheme should resolve the problem arising from the second case described in the previous paragraph while still retaining the positive aspects of the original regional scoring approach.

Algorithm 3 Modication for Regional Scoring function score_region(core) (1) make a new temporary component tempComponent based on core (2) set neighborhood to first neighbors of the core (3) sort neighborhood nodes based on score (4) initialize variable idN to 0 and score_increase to 1 (5) set variable previous_score to the score of tempComponent (6) WHILE idN < number of neighbors AND score_increase > 0 DO (7) add node idN to tempComponent (8) set new_score to be the score of tempComponent (9) set score_increase to new_score - previous_score (10) IF score_increase > 0 (11) set previous_score to new_score (12) increment idN by 1 (13)return previous_score

2.4 Running JAM over Multiple Trials

The simulated annealing algorithm employed by JAM depends on randomness as part of the search process and, because of this randomness, it is necessary to run the search process 19

Figure 2.1: An example of the distribution of nodes resulting from a JAM search over ten runs shows inconsistency in the subnetwork results. This distribution is dominated by many single node appearances across runs although a signicant number of nodes that consistently appear in each run also exists.

multiple times and to look for agreement in the results. An example of this randomness is shown in Figure 2.1. In this example, the majority of nodes show up at a rate of fewer than ten occurences over ten runs, but it also shows signicant number of nodes with perfect occurences. These results show great inconsistency of JAM results across runs, This example motivates the development of a statistical method to lter the results from multiple JAM runs to select consistent nodes. In this subsection, a new statistical method to nd the agreement over multiple runs of JAM will be described. This method is required to lter the results from multiple JAM runs to determine which group of nodes are most strongly supported by the search algorithm results.

The idea behind this method comes from the binomial distribution. The binomial distribution is the discrete probability distribution of the number of successes in n independent trials. In the case of nding active subnetworks, success is dened as a node appearing in a subnetwork result of a JAM search. The probability of success p would be dened as the probability that a node comes up as a result of JAM search, which in this work is dened 20

as the maximum number of nodes returned from any JAM run divided by the total number of nodes in the network. Based on the cumulative binomial distribution, it is also possible

to determine the probability of a node showing up x out of n times by chance, which is an important probability for determining a signicant node. Essentially, this ltering process identies how many times a node needs to show up in the results from multiple runs to be considered signicant.

Since the JAM process is not dealing with just one node, it is necessary to apply the ltering process multiple times - essentially once to every node in the graph. It is common to use a correction to the statistical signicance when applying a test multiple times. One common correction is the Bonferonni correction (Bonferroni, 1936). This method suggests

using a stricter signicance level α equal to the original signicance level α divided by the number of signicance tests employed, where the signicance level is dened as the acceptable probability threshold for making Type I error. This correction is shown in Equation 2.1.

α ≤ α , where n is the number of tests (2.1) n per significance test Table 2.1 shows an example of the results obtained from using this process to determine how many times a node must be part of an active subnetwork across ten dierent runs to be deemed signicant. This example shows ten independent runs of JAM. The rst column is the number of times a node could be selected by a JAM search in ten runs. The second column is the probability that there are exactly x out of n successes, or, in this case, that a node would show up by chance x out of 10 runs in the JAM results. The third column is the cumulative probability of the number of successes listed in the rst column (less than or equal to x out of n successes). The fourth column is the probability that there are x or more successes from n trials. Essentially, we are interested in the fourth column as it indicates the probability that a node shows up equal to or more than x out of 10 times if an algorithm is choosing randomly.

In the example shown in table 2.1, for a given node, there is a 0.002242082 chance that it shows up in greater than or equal to 7 output subnetworks if the algorithm chooses randomly. 21

Table 2.1: Example of binomial distribution over 10 JAM runs with p : 624/2691. # of successa binomial distb cum binomial distc p-valued multiple test correctione 0 0.070804944 0.070804944 1 1352 1 0.214643558 0.285448502 0.929195056 1256.271716 2 0.292809154 0.578257657 0.714551498 966.0736251 3 0.236705124 0.814962781 0.421742343 570.1956482 4 0.125574074 0.940536855 0.185037219 250.1703201 5 0.04568099 0.986217846 0.059463145 80.3941714 6 0.011540073 0.997757918 0.013782154 18.63347267 7 0.001999055 0.999756973 0.002242082 3.031294538 8 0.000227253 0.999984227 0.000243027 0.328572017 9 1.53092E-05 0.999999536 1.57733E-05 0.021325474 10 4.64094E-07 1 4.64094E-07 0.000627456 a : the number of times a node shows up in the subnetwork results over multiple JAM runs (k). b : the probability that a node shows up in k subnetwork results over n JAM runs. c : the probability that a node shows up less than or equal to k times over n JAM runs. d : the probability that a node shows up k or more times over n JAM runs. e : the bonferroni correction of the value dened in d to support multiple comparisons.

Thus, getting a node seven times out of ten trials is a rare occurrence at the 0.05 signicance level. However, since more than one node must be examined, repeated tests of signicance are employed. This is the place where the Bonferonni correction plays its part. Assuming there exist 1352 unique nodes from ten runs with α of 0.05, the new α after the correction would be 0.05 divided by 1352. The other way to look at this correction is to multiply the p-value of interest with the number of unique nodes yielding the fth column of Table 2.1.

After the correction, in the example above, a node would be considered signicant under α of 0.05 if it appears nine or more times in the output subnetworks from ten runs of JAM.

2.5 Sensitivity and Specicity

This section will describe the sensitivity and specicity metrics used to compare the results of the modied version of JAM and the original version of JAM. In order to compare the results based on these metrics, a common standard needs to be dened, against which each algorithm's output will be compared. In the case of JAM, given a network and a gene 22

expression dataset, the standard will be dened as a 'signicant genes list', a list of genes that surpass particular criteria for signicant changes in level of expression.

In a JAM run, a true positive gene is dened as a gene that shows up in a JAM result and in the standard signicant genes list. Genes that show up in JAM results but not in the signicant genes list are denoted as false positive genes. Genes that are not picked up by the JAM algorithm but are contained in the signicant genes list are denoted as false negatives genes. The rest of the genes from the expression dataset that don't show up in both the JAM result and the signicant genes list are denoted as true negatives genes.

# of true positives Sensitivity = (2.2) # of true positives + # of false negatives

# of true negatives Specificity = (2.3) # of true negatives + # of false positives Sensitivity is dened by the number of true positives divided by the number of true positives plus the number of false negatives (Equation 2.2). This metric indicates the percentage of actual positive examples to labeled correctly as a positive example by a binary classica- tion algorithm. A high sensitivity score correlates with low false negatives meaning that the algorithm doesn't miss many of the positives results it should detect. Specicity is dened by the number of true negatives divided by the number of true negatives plus the number of false positives (Equation 2.3). This metric indicates the percentage of actual negative examples labeled as negative examples. High scores in specicity correlates with low false positives meaning that the algorithm doesn't bring many negative examples to the results. Chapter 3: Method Validation

In this section, results from executing JAM with each modication outlined in Section 2 are compared to results from executing the original version of JAM. Modications are tested independently at rst, and tests for all version of JAM are executed on the same networks and expression data. For the following subsections, these parameters are used: number of

iterations N; starting temperature Tstart; end temperature Tend; and number of subnetworks tracked M.

3.1 Networks

The galactose utilization network, mouse cell-cycle network, and tadpole network are used as inputs for JAM search to validate the rst, the second, and the third modication respectively. The following describes the networks used in this section :

• Galactose utilization pathway (Figure 3.1a) : This network consists of 332 genes and 361 protein-protein and protein-DNA interactions from previous study (Ideker et al., 2001), and was used in the original JAM paper. Gene expression changes were measured for wild type yeast versus a strain responding to a complete deletion of the GAL80 gene (provided in the same publication). In this dataset, 77 out of 332 nodes

were labeled by Ideker as having signicant expression changes (p-value < 10−5).

• Mouse cell-cycle network (Figure 3.1b) : This network is the part of the KEGG Network (Kanehisa and Goto, 2000) that only include genes labeled by KEGG as mouse cell- cycle process. It contains 117 nodes with approximately 80% of the nodes having no change in expression (negative Z-score).

• Tadpole network (Figure 3.1c) : This network was specically designed in this work to show the problems in the regional scoring heuristic implemented in the original

23 24

version of JAM. In this network, there is a high-scoring hub that surrounded by many low-scoring neighbors to represent one of the possible combination in regional scoring in which high-scoring core with low-scoring neighborhood. This network also contains with a relatively high-scoring tail region (node 9 - 12) that seperated from the hub with a low-scoring connecter node (node 3) that are part of the low-scoring neighborhood surrounded the hub (node 5).

(a) Galactose utilization pathway

(b) mouse cell-cycle network (c) Tadpole network

Figure 3.1: Various networks used for validation purposes. Negative scores are represented by white nodes. Increasing positive scores represented by the gradation of color between white and blue. 25

3.2 Validation for randomizing initial list of subnetworks

As described in the previous section, the suggested modications are based on the perceived incorrect implementation of JAM. The rst modication made was to add additional randomness to the JAM search starting point, expecting the search to explore a wider set of subnetworks and have a better chance of obtaining better scoring networks. The modication was made by toggling each node on/o with probability of 0.5 at the beginning of the search. In order to determine the impact of this modication, the results returned from the original JAM implementation and the modied JAM were compared. One hundred runs were made with both versions of JAM on galactose utilization network and the ve highest scoring subnetworks were extracted from the results of each run. Each run was executed

with parameters (N = 100000; Tstart = 2; Tend = 0.01).

(a) (b)

Figure 3.2: Randomizing the initial list of subnetworks neither improves overall scores nor prevents unusually low scores. The top-score comparison shown demonstrates two things: the modication does not result in signicant score improvements, and cases exist for both versions of JAM where unusually low scores are returned. As shown in Figure 3.2a, the search ends up with a low-scoring subnetwork at run 12, 32, and 56. The same case also happens in the modied version of JAM as shown in Figure 3.2b, with runs 29, 49, and 95 demonstrating the drop in score.

As can be seen in Figure 3.2, the modication does not provide signicant score improvement over the original version of JAM. If we dig deeper and compare the progression of the 26 size distribution along the iteration space for both versions of JAM runs, the size distribution from the original JAM algorithm, as shown in Figure 3.3a, quickly reaches the starting point of the size distribution in the graph labeled in Figure 3.3b. From these runs, the evidence suggests that our initial belief that the original version of JAM does not performs enough sampling of the subnetwork space at the beginning of a run was incorrect.

(a) (b)

Figure 3.3: The progression of size-distribution from original JAM (3.3a) quickly reaches the starting point of size-distribution from modied JAM (3.3b). The size distribution in graph (3.3a) is shown to quickly match the starting point (indicated by red arrow) of the size distribution in graph (3.3b). This example suggests that the original algorithm does enough sampling of the state space, even when starting with a network with all nodes toggled on, to match the performance of the modied algorithm. The red line shown on both plots represents the size of of the subnetwork list that the search converges to in cases where high scores are returned.

The second interesting fact that can be extracted from Figure 3.2 is that there are several instances for both versions of JAM where the search doesn't end up with a high-scoring subnetwork. In order to understand why the search can produce results that have signif- icantly lower score than other runs, it is necessary to look into the score distribution and size distribution for both results at the iteration level. From the observed iteration space of score distribution and size distribution that leads to a low scoring instance as shown in Figure 3.4a and Figure 3.4b, the score distribution peaks when the size distribution enters its valley, at around iteration 45000. Starting from halfway through the iteration, the score 27 distribution moves downward and then atten, while the size distribution does the reverse. This example suggests there is a relationship between subnetwork scores and the number of subnetworks. Furthermore, as shown in Figure 3.4d, the nal size of the subnetwork list for the high-scoring example is very similar to the size associated with valley region in the middle of the iteration space in the low-scoring example. This example suggests there is an ideal number of subnetworks to track in order to achieve high-scoring subnetwork results. Based on these observations, it is hypothesized that a breaking of the network into a large number of toggled-on subnetworks can lead to search failure. It is anticipated that the second modication, constraining the number of subnetworks tracked, will resolve this issue. 28

(a) (b)

Figure 3.4: Graphs of the iteration space of modied JAM runs in term of size distribution and score distribution that lead to high-scoring subnetworks and low-scoring subnetworks, show a relationship between size and score. (3.4a) and (3.4b) depict the score distribution and the size distribution respectively that lead to a low- scoring subnetwork result. Graph (3.4b) shows a decrease in size when the score in (3.4a) is at its peak, followed by an increase in size and a decrease in score. When the score distribution in (3.4a) goes steady and low, the size distribution in (3.4b) is also consistent along the red line. (3.4c) and (3.4d) depict the score distribution and the size distribution respectively that leads to a high-scoring subnetwork result. Both graphs show the same pattern in terms of reaching stability halfway through the end of iterations space. The patterns from graphs (3.4a) & (3.4b) and the patterns from graphs (3.4c) & (3.4d) suggest there exists a relationship between the size of the subnetworks list and the return of the high-scoring subnetworks. 29

3.3 Validation for Limiting the Size of the Subnetwork List

In the previous subsection, it was suggested that the unconstrained number of subnetworks tracked perturbs the search, trapping the search solution to a large number of low-scoring active subnetworks. To obtain further evidence to support this initial observation, JAM search was executed on the test network which has a majority of low scoring nodes, the mouse cell cycle network. One hundred runs were made with both the original and the modied versions of JAM and the ten highest scoring subnetworks were extracted from the

results of each run. Each run was executed with parameters (N = 100000; Tstart = 2;

Tend = 0.01; M = 10). The size of the list of subnetwork was recorded at each iteration pre-truncation to the user dened maximum list size M. The plot in Figure 3.5 shows how modied JAM consistently nds higher scoring subnetworks relative to the generally low- scoring subnetworks found by the original JAM. The progressions of the size and the score distribution that show the relationship between size and Z-score are illustrated in Figure 3.6.

Figure 3.5: Top score distribution from original JAM (green) shows consistently higher Z-scores than Z-scores from modied JAM (red) over one hundred JAM runs. In a network with a majority of low scoring nodes, the original JAM consistently returns low-scoring subnetworks relative to those returned by the modied JAM approach. 30

(a) (b)

Figure 3.6: Tracing the iteration space of size and score distribution demonstrates how the size of the list of tracked subnetworks aects the performance of the search. As the iterations progress, the plots in Figure (3.6a) demonstrate movement to higher scoring states by the modied version of JAM while the original JAM search stagnates around one score. The plots in Figure (3.6b) show the progression of the size of the list of tracked subnetworks maintained by each version of the JAM algorithm. While modied JAM (red) limits the subnetwork growth to a certain number, the sizes maintained by the original JAM grow until it hits a point where it stabilizes because it can not nd better subnetworks in which to move.

The correction to limit the number of tracked subnetworks is one of the crucial steps to improve a JAM search. Keeping track of subnetworks while searching seems like a minor detail in the search process but the impact of this particular step is surprisingly important to guide the search toward high scoring subnetworks. In order to illustrate this improvement, both original and modied JAM search are executed on the mouse cell-cycle network and the top scoring scoring subnetwork from each run is extracted from the results. The mouse cell-cycle network is dominated by many low scoring nodes as illustrated in Figure 3.7a and is used because the search procedure is expected to fail when the network is broken into many low-scoring subnetworks. The result from modied JAM is compared with the result from the original JAM. From Figure 3.7b and Figure 3.7d, it can be seen that the subnetwork result from the original JAM could not connect as many high-scoring nodes together as compared to the subnetwork result from the modied JAM. The reason behind the poorer result from the original version of JAM is because at the end of the iterations of the search process, there 31 are too many low scoring nodes that are active which hinders the higher scoring subnetwork being found. This is highlighted in the graph in Figure 3.7c, which shows the number of active subnetworks the original JAM still kept track of at the end of the search iterations. This result provides evidence that maintaining an unconstrained number of subnetworks can lead to poorer performance from the search process. 32

(a) Mouse cell-cycle network (b) Top-scoring subnetwork result from original JAM

(c) All nodes active at the end of iterations of (d) Top-scoring subnetwork result from modied an original JAM search JAM

Figure 3.7: Examples of the state of active nodes achieved for the mouse cell cycle network as a result of employing the original JAM algorithm and the JAM algorithm with only the modication to limit the size of the tracked subnetwork list. Nodes with negative Z-scores are represented by the white nodes. Active nodes are represented by yellow nodes. Increasing positive Z-scores are represented by the gradation of color between white and blue. Figure 3.7a depicts the initial condition of the mouse cell cycle network before the JAM search being employed. Figure 3.7b highlights a top-scoring subnetwork as a result of original JAM search. All nodes active at the end of iterations (including a top-scoring subnetwork from Figure 3.7b) are illustrated in Figure 3.7c. Figure 3.7d depicts a top-scoring subnetwork achieved by executing modied version of JAM with limiting the size of tracked subnetwork list. 33

3.4 Validation for Improved Regional Scoring

The third improvement discussed in Section 2.3 is directly related to the regional-scoring heuristic of the original JAM approach. As was stated earlier, the problem with the current regional-scoring heuristic is when the algorithm tries to score a subnetwork with a high- scoring core and a low-scoring neighborhood. Figure 3.8 serves to illustrate this case. In this gure, there exists a specically designed network (tadpole network) that has a high-scoring hub (node 5) surrounded by many low-scoring nodes (nodes 0-4 and 6-8) that are highly connected to each other. This hub node will serve as an example of a good core with a bad neighborhood. There is only one way to connect the high-scoring hub with the rest of the high-scoring nodes in the tail, which is through the low-scoring connector node. One hundred runs were made with both versions of JAM and the top ve subnetworks (or all subnetworks if fewer than ve were returned) were extracted from the results of each run.

Each run was executed with parameters (N = 100000; Tstart = 2; Tend = 0.01; M = 5). The result from those runs for both version of JAM can be seen in Figure 3.8 and Table 3.1. As can be seen in Figure 3.8, the modied JAM is able to connect the hub region and the tail region together while original JAM can't connect both subnetworks together. Instead of combining the hub and the rest of the tail subnetwork into a high-scoring subnetwork, original JAM gives a bad score to a hub node because regional scoring forces the hub node to grab its neighbors and score the hub and its neighbors as a region. The new JAM works around this problem by analyzing each neighbor and only including neighbors that give score improvement. A more detailed representation of how often modied JAM and original JAM hit dierent results is shown in Table 3.1.

The rst column of Table 3.1 shows the sets of nodes that make a subnetwork. The second column shows how many times the subnetwork in the rst column is chosen by the original JAM algorithm over 100 runs. The third column shows the same meaning as the second column but with modied JAM. Looking at the Table and Figure together, the returned subnetworks are essentially the combinations of two-nodes near the hub or the combinations 34 of two to three tail nodes. Over 100 runs, nodes in the hub and tail are never combined together. On the other hand, the results from modied JAM show a clear bias to connecting the tail and hub area together, leading to better overall results since the hub and tail together constitute the highest scoring networks of any combination seen.

Figure 3.8: The subnetwork result from modied JAM with improved regional scoring (red bordered) shows better connectivity compared to the result from the original JAM (dashed orange border) on the tadpole network. The gradation of the color of the node from white to blue represents the Z-score of the node with white being the lowest and blue being the highest. The subnetwork bordered by red is the optimal result (as computed by brute force analysis of subnetwork score) and the result most commonly encountered by the modied JAM search, while the subnetworks circled by dashed orange lines are the possible combination of results encountered by the original JAM search.

Table 3.1: Subnetworks distribution over 100 runs Subnetworka Original JAM hits Modied JAM hits {5} 0 2 {0,5} 36 0 {1,5} 30 0 {2,5} 42 0 {4,5} 43 0 {6,5} 40 0 {7,5} 44 0 {8,5} 47 0 {11,10} 46 2 {11,12} 1 15 {11,12,10} 54 0 {3,5,9,10,11} 0 16 {3,5,9,10,11,12} 0 82 a The numbers in the set correspond to the node numbers from Figure 3.8. 35

3.5 Modied JAM Result with All Modications Active

(a) (b)

Figure 3.9: The modied JAM results oer an increase in sensitivity and decrease in specicity compared to original JAM results over ten runs on galactose utilization pathway. Sensitivity and specicity for original JAM (solid) and modied JAM (dashed) respectively are shown in Figure 3.9a and Figure 3.9b. The averages on both graph are plotted with horizontal solid lines for original JAM and dashed red lines for modied JAM.

It is important to observe how the three modications combined together aect the overall results. The galactose utilization network is used as a benchmark to compare the results from the improved JAM and the original JAM. This network is used because it was employed in the original JAM paper to measure their algorithm performance. The sensitivity and specicity metric are used to compare the performance of original JAM and modied JAM. For each version of JAM, the nodes in the top ve subnetworks are combined together into a list of genes. This genes list is compared to the 77 genes with signicant expression indicated in the original JAM paper. As can be seen in Figure 3.9, applying all three improvements to JAM increases sensitivity but decreases specicity. On average over ten runs, modied JAM results in a sensitivity improvement of 0.11 or 23.36% increase over the original sensitivity and specicity degradation of 0.03 or 3.38% decrease over the original specicity.

Based on this result, 23.36% increase in sensitivity means the result from modied JAM algorithm contains 23.36% more signicant genes than the result from original JAM algorithm. This result is accompanied by 3.38% decrease in specicity which is the penalty 36 number of genes required to grab more signicant genes into the results. Although there seems to be a trade o between sensitivity and specicity, the trade o is important for the modied JAM algorithm to obtain better score and bring more signicant genes to the results. Finding additional signicant genes returned by the search will allow better understanding of the network context in which these signicant genes are placed. In addition, getting a few more false positive genes is not a signicant problem, as these genes themselves may reveal a connection to other signicant gene regions. Chapter 4: Biological Results : Identication of Active Subnetworks from Time Course Microarray Data

The modied JAM algorithm were executed on gene expression data from a real biological experiment and a biological network derived from the KEGG database. This chapter will describe the microarray datasets resulting from biological experiments, describe the process of, and results from, applying JAM to these biological data, and discuss an interpretation of the result.

4.1 Datasets Description

4.1.1 Mouse KEGG Network

KEGG (Kanehisa and Goto, 2000) is a publicly accessible database that contains interaction data from large scale datasets derived from genomics, transcriptomics, proteomics, and metabolomics experiments. Interaction data from KEGG can be translated into a network where a node represents a gene or gene product and edges represent the interactions between genes/gene products. KEGG divides these relationships into three main types : protein-protein interactions, gene expression relationships, and enzyme-enzyme relationships. Proteins-protein interactions are divided again into several subtypes, such as phosphoryla- tion, dephosphorylation, methylation, activation, inhibition, association, dissociation, and complex relationship. In gene expression relationships, there are expression and repression subtypes. An enzyme-enzyme relationship shows the relationship between successive reaction steps in metabolic pathways. The network containing the combination of mouse metabolic, signaling, and transcriptional pathways was extracted from the KEGG database release 49.0. This network, a directed graph containing 2691 nodes and 27813 edges, was extracted from KEGG into Cytoscape to be manipulated by using the BioNetBuilder Plugins (Avila-Campillo et al., 2007).

37 38

4.1.2 Dendritic Cell Microarray Data

Dendritic cells (DC) were collected from the bone marrow of wild type mice. DC were treated with Poly:IC to mimic viral infection, then they were harvested at 0 (control time point), 1, 3, 6, 12, and 24 hours time points. Microarray analysis on these experiments was performed using Aymetrix mouse genome 430 2.0 that consists of 45101 probe sets. Each probe set is identied by a unique ID called an Ay ID. The reported values from this experiment include change p-values and Signal Log Ratio (SLR) for each Ay ID. SLR values represent the magnitude and the sign of dierentially expressed genes at a certain time point compared to the control time point in log base 2, while the change p-values represent the signicance of the increase or decrease. Positive SLR indicates expression and negative SLR indicates repression. Change p-values greater than or equal to 0.998 indicate signicant increase, while values less than or equal to 0.002 indicate signicant decrease. Details about computing SLR and change p-value can be found in (Olex, 2007).

4.2 Conversion from Signal Log Ratio to p-value

JAM requires the p-value of each gene as an input for the simulated annealing algorithm. Thus, it is necessary to convert the SLR of each gene to a p-value. Equation 4.1 is used to compute the area under the assumed normal curve from negative innity to a given SLR value x. Since a low p-value represents signicant expression change compared to control (positive or negative change) and a high p-value represents otherwise, a slight modication is needed for the conversion process from SLR to p-value. Given the mean and standard deviation of the SLR values across a microarray experiment, the p-value computed from SLR in this work is the addition of the area under the curve from negative innity to the negative

SLR value of x with the area from the positive SLR value of x to positive innity (Equation 4.2). In this scheme, SLR values with high absolute magnitude will have small p-value and SLR values close to zero will have large p-values. 39

x 1 (x − µ)2 Φ(x, µ, σ) = √ exp(− )dx (4.1) σ 2Π ˆ 2σ2 −∞

pvalue = 1 − |Φ(x, µ, σ) − Φ(−x, µ, σ)| (4.2)

4.3 Conversion from Ay Id to Entrez ID

Expression data from Aymetrix uses the Ay ID eld described in Section 4.1.2 as its primary identier. In the process of overlaying expression data to the KEGG network, it is necessary to convert Ay IDs to the Entrez IDs used as node identiers by KEGG. The relationship between Ay ID and Entrez ID is many to many. As a result, there are two cases to be considered. First, a case where one Ay ID has multiple Entrez IDs. In this case, multiple nodes in the KEGG network will have the same expression value. The other case is when multiple Ay IDs map to one Entrez ID. In this case, an aggregate function, such as maximum or average, is chosen to obtain a single value. In this work, maximum was chosen to prevent loss of signal.

Aymetrix provides a tool called NetAx to map Ay IDs to other annotations, such as gene symbol, gene title, GO terms, and other IDs. The conversion process from Ay ID to Entrez ID employed in this work used NetAx to provide mapping information from Ay ID to Entrez ID. The overall process from Ay ID-Entrez ID conversion to connecting gene expression data with the corresponding Entrez ID is illustrated in Figure 4.1. In step one, the table represents the mapping from Ay ID to Entrez ID which is provided by NetAx. Since the eventual goal is to associate gene expression data with Entrez IDs, Entrez IDs must be dened as keys for the mapping. For Entrez IDs to work as keys, this rst table must be manipulated such that each Entrez ID is uniquely present in the table and no row has multiple Entrez ID entries. Step two from Figure 4.1 eliminates the problem of multiple Entrez IDs in one row. It does that by duplicating Ay ID that are associated with multiple Entrez IDs and inserting a new row for each association between Ay ID and 40

Entrez ID to the table. The nal step is to make sure the Entrez IDs are unique for each row of the table and correspond to gene expression values. In the case where one Entrez ID is associated with multiple Ay IDs, uniqueness is obtained by grouping the Ay IDs together and using a maximum aggregate function to extract a single timeseries from the set of timeseries associated with the multiple Ay IDs.

As a result of using the maximum aggregate function at the nal step described in the previous paragraph, there are cases where one Entrez ID takes gene expression values from dierent Ay IDs at dierent time points. For example, Entrez ID 99982 get gene expression information at time point 3, 6, and 12 from probe set number 1426762_s_at and the remaining expression information from probe set number 1426761_at. 41

Figure 4.1: An example of conversion from Ay ID to Entrez ID. (1) The format obtained from NetAx. If an Ay ID corresponds to multiple Entrez IDs, the Entrez IDs will be seperated by ///. (2) For all Ay IDs that have multiple Entrez IDs, insert a new Ay ID-single Entrez ID pair for all available Entrez IDs. (3) Gene expression data from DC microarray chip. (4) This nal table shows the association between Entrez IDs and collected gene expression data. The maximum aggregate function will be used in the case where one Entrez ID corresponds to multiple Ay IDs.

4.4 Overall Process

The overall process of running JAM to extract active subnetworks from the KEGG network is shown in Figure 4.2. This process requires two inputs : the biological network derived from KEGG and the p-values of expression for each KEGG node. Since KEGG uses Entrez ID as the identier for nodes, it is necessary to convert the Ay ID supplied by Aymetrix to the Entrez ID recognized by KEGG. This rst process is described in detail in Section 4.3. As can be seen from step one of the process, 45101 Ay IDs are converted into 23338 Entrez 42

IDs with 6213 Ay IDs not having an association with any Entrez ID. This 6213 Ay IDs contains approximately 20% of the signicant nodes (nodes with expression p-value below 0.01) in this dataset. The next step of this overall process is to convert the SLR value for each gene to a p-value required by JAM as an input. This conversion method is described in Section 4.2. The third step of this process is to overlay the expression values obtained from the DC microarray data and the p-values obtained from step two on top of the KEGG network. From all nodes in KEGG, 105 nodes were assigned zero SLR because there is no association between these nodes to Ay IDs on the microarray chip. The third step acts as a checkpoint before the JAM search algorithm can be applied to the data.

After all the required inputs for JAM were collected, ten JAM runs were executed for each time point. At each time point, the top-scoring subnetwork from each run is extracted from the results (Step 5). At this point, ten top-scoring subnetworks are now available, collected from the ten runs. To extract only the nodes that appeared consistently across multiple JAM runs, the statistical analysis described in Section 2.4 was employed (Step 6). The group of nodes that pass the statistical test are nodes that are part of an active subnetwork and are predicted to be the group of genes that play important roles in DC maturation process. This signicance testing lters out the group of genes that do not consistently show up in the JAM results. As a consequence, the group of genes after the ltering process might not be just one big active subnetwork, but instead several smaller active subnetworks with high consistency across multiple runs. 43

Figure 4.2: Proposed JAM search with DC data and KEGG network as an input. (1) Conversion step from Ay ID to Entrez ID. This step decreases the number of IDs from 45101 Ay IDs to 23338 Entrez IDs with 6213 Ay IDs going unused because they have no association with an Entrez ID. (2) Conversion from SLR to expression p-value required by JAM. (3) Overlaying gene expression data on top of KEGG network. 105 nodes don't have expression values because there is no association between these nodes to Ay ID. (4) Running JAM for each timepoint multiple times. (5) Extract top-scoring subnetworks from each of the runs in step 4. (6) Statistical lter to obtain consistent nodes across multiple runs. The nal results is the group of nodes that pass the statistical lter at step 6. 44

4.5 From Subnetworks to Pathway Annotation

Based on the overall process described in Section 4.4, modied JAM was executed ten times per timepoint on the mouse KEGG network with parameters (N = 1000000; Tstart = 2;

Tend = 0.01; M = 5). After the statistical ltering process was applied, the nal results contain 202 , 176 , 147 , 79 , and 92 genes respectively composing the 1, 3, 6, 12, and 24 hour time-point active subnetworks. The DAVID functional annotation tool (Dennis et al., 2003) was used to nd the most signicant over-represented pathways with respect to the gene lists returned by the JAM search, with pathway results ltered by employing a p-value threshold of 0.05. The pathway annotations shown in Tables 4.1 - 4.5 provide information about the p-value (the probability that a similarly sized randomly selected group of nodes would have the same percentage of nodes with the annotation of interest) for each annotated pathway, the total number of nodes in the subnetwork belonging to that pathway, the actual total number of nodes in the pathway as labeled by KEGG, the percentage of the KEGG- labeled pathway which this subnetwork composes, and the percentage of the subnetwork with this pathway annotation.

As can be seen from Table 4.1 through 4.5, there is a wider variation of pathways that are signicantly over-represented at the early early time point, and then the pathways start to be more specic, as indicated by fewer signicant pathway entries at later time points. This result suggests broader and more gene activity at early time points, followed by less, but more specically purposed gene activity at later time points. The wave of pathway annotation across time points is shown in Table 4.6. There are pathways that are annotated as signicant at almost all timepoints, such as the Jak-STAT signaling pathway, the calcium signaling pathway, and the TLR (Toll-like Receptor) signaling pathway. There are also pathways that are annotated as signicant from middle to late time points, such as antigen processing and presentation.

Even though the approach to looking at pathway annotations is a good start to understand biological processes behind this experiment, it is still necessary to look inside the 45 pathway to obtain more insight of what really happens on a gene by gene basis. The TLR pathway has been chosen as an example of a pathway to be observed in more detail as it is annotated as signicant at all time points in the experiment. Looking at the number of genes in the per time-point TLR pathway results shown in Figure 4.3, it appears that the peak of gene activity happens between the 3 hour and 12 hour timepoints and the activity appears to be receding at 24 hours.

At the 1 hour time-point , there is a small group containing interferons and Cxcl10 (IP- 10) that is active, Interleukin 6 and 12 are detected, and a small group of genes that also belong to the MAPK pathway are present. At the 3 hour time-point, the results indicate more members of the Cxcl family, Cxcl11 and Cxcl12 are active, along with CD80. This time point also brings a STAT1-Cxcl subnetwork to the surface. At the 6 hour time-point, the subnetworks grow bigger and start to include the large family of interferon alpha and beta. At this time point, IRF3 connects this to CD40 and CD80 as well as to the STAT1-Cxcl subnetwork. At the 12 hour time-point, the network starts to break apart. CD86 is indicated to be active, while CD40 and CD80 no longer are. The connection between the group of interferons and STAT1-Cxcl is also broken. At the nal time-point, there is little activity left.

The previously discussed interleukin genes, interferon genes , CD40, CD80, CD86, and Cxcl genes (IP-10, MIG, I-TAC) are the end products of the TLR signaling pathway as summarized by the KEGG TLR map (Kanehisa and Goto, 2000) in Figure 4.4. As can be seen from the map, the wave of gene activity starts nonuniformly. For example, there is a gene activity that start right in the middle of the pathway (e.g : start with Map2k4 (MKK4) and Map3k7 (TAK1)), another one that starts at the beginning of the pathway (e.g : start with Rac1 -> PI3K), and there are some genes that are starting at the end of the pathway and loop back to the beginning of the pathway(e.g : IF-alpha -> IFNAR -> STAT1). Generally, the wave of gene activity can be seen to move towards the right side of the map and it appears to loop back to the bottom left corner of the map at the 24 hour timepoint. Less gene activity in the left portion of the map suggests the activity of genes in 46 that area might occur before the 1 hour timepoint.

Table 4.1: 1hr DAVID annotation result.

Table 4.2: 3hr DAVID annotation result

Table 4.3: 6hr DAVID annotation result

Table 4.4: 12hr DAVID annotation result 47

Table 4.5: 24hr DAVID annotation result

Table 4.6: Summary of the results from Table 4.1-4.5 48

Figure 4.3: Genes labeled as TLR signaling pathway across timepoint. Nodes color gradation from white to blue denotes positive dierential expression with blue being the node with the most positive expression changes. Node color gradation from white to red denotes negative dierential expression with red being the node with the most negative expression changes. White nodes denote no change in expression. Orange edges denote gene expression relationship and blue edges denote protein interaction relationship. Edges with arrow head shows directional relationship between genes. 49 . The green box represents proteins involved Dynamic of gene activity in toll-like receptor signaling pathway Figure 4.4: in this pathway.subnetwork The with the ve 1-hour colored timepointcolor boxes being box being beside the active left the and mostbin/show_pathway?mmu04620 white protein box being and box inactive. going show Pathway to map at the extracted right what from until KEGG timepoints the database this 24-hour at time http://www.genome.jp/kegg- protein point, was with part the red of an active Chapter 5: Conclusion and Future Work

5.1 Conclusion

In this work, three modications were made to the original JAM algorithm, and varying results were realized with each modication. The rst modication, to randomize the initial list of subnetworks in the search, did not provide the signicant score improvements over the original JAM approach that were expected. The reason behind this is because the size of the initial list of subnetworks under the original JAM approach quickly reaches the size of the random initial subnetworks of modied JAM. The second modication, limiting the size of tracked subnetworks, is an important modication as it has been demonstrated to decrease the probability of the JAM search process getting stuck in a region of low-scoring subnetworks. This modication also allows more exibility in terms of maintaining the list of subnetworks by allowing parameterization of the size of the list of tracked subnetworks. This extra exibility is important because the ideal number of tracked subnetworks is unknown and the original JAM approach doesn't give control to the user over the size of the list of tracked subnetworks. A third modication was the development of an improved regional scoring heuristic which revises which neighbors of the neighborhood around a node are included in the regional score for that node. This improved heuristic leads the search to keep subnetworks which have good core scores but have low-scoring neighbors, a case which is not handled well by the original algorithm, as it would commonly drop those subnetworks from the subnetworks list during search. The subnetwork results from employing the version of JAM with these three modications have been compared to the subnetwork results from employing the original JAM on the same networks, and the modied version of JAM has been shown to increase the sensitivity of the search while only suering a minor loss in the level of specicity. Overall, it is believed that the experiments in this work provide evidence that the use of the developed modications to JAM increase the probability of nding the

50 51 subnetworks which contain the key genes undergoing signicant changes of expression.

Because of the stochastic nature of the JAM algorithm, it is argued that it is necessary to run JAM multiple times to obtain consistent active subnetworks. The developed statistical ltering method has been employed after execution of JAM to combine subnetworks results from each run and extract consensus subnetworks. This postprocessing step eliminates set of genes that are not consistently acquired by multiple JAM runs. In addition to ensuring consistency, this ltering approach can potentially reduce the size of the subnetworks resulting from JAM into smaller active subnetworks. Smaller subnetworks are easier for biologists to visualize and analyze on a gene by gene basis.

The subnetwork results returned from the process employed in Chapter 4 are dominated by a majority of up-regulated genes. This result is supported by the previous work on the same dataset by Amy Olex (Olex, 2007) which reported a majority of up-regulated genes with high fold change (>= 4-fold change). Pathway annotations from the subnetwork results provide helpful information to biologists to relate gene expression data with the pathways involved in cellular processes. Such results provide a high-level overview of the cellular mechanisms triggered by a certain stimulus when observed across time points. In order to gain further insight into these underlying biological processes, it is still necessary for a biologist to observe gene expression data from the extracted subnetwork results in a more detailed manner. The specic subnetwork results presented in Chapter 4 are currently under review by a biologist as a rst step in experimental validation.

5.1.1 Comparison to other methods

Previous work by Rajagopalan et. al. focused on nding active subnetworks of smaller, visually-interpretable size than the original JAM (Rajagopalan and Agarwal, 2005). Their work employed a greedy-based approach as their searching algorithm. This approach has a signicant problem, the possibility of being trapped in local maxima, while JAM employed a simulated annealing approach whose underlying stochastic algorithm allows the chance to escape from local maxima. In addition, as presented earlier in Chapter 4, the subnet- 52 work results from modied JAM algorithm indicate subnetworks are dominated by fringe nodes. The postprocessing statistical lter after multiple runs of modied JAM algorithm can eliminate the fringe nodes and return smaller and more interpretable subnetworks.

In other previous work, Dittrich et. al. proposed a method to search for an optimal scoring subnetwork based on an integer linear programming (ILP) formulation (Dittrich et al., 2008). Their tool is unique because it required the use of a licensed ILP solver to address the problem. Although they show that this method performance, timewise, is relatively acceptable in practice, the theoretical complexity of this approach is bounded by exponential time with respect to the number of vertices. However, JAM search process is bounded by polynomial time with respect to the number of vertices. Since this method was geared toward nding an optimal solution, it designed to produce one subnetwork as the result. To be able to get multiple subnetwork, as natively done by JAM, it required manual separation of the input network into connected components based on the topology of the network. It is often not easy to perceive how to dene such components in huge networks. However, the optimality of the result oered by this method allows a good standard for comparison with other methods.

Two other similar approaches try to nd gene modules whose genes have a similar expression pattern. While these are also using expression data and interation data, these approaches are actually solving a dierent problem than JAM. A method developed by Ulit- sky et. al. looked for coexpressed genes that are connected in the network and which also correlated with clinical parameters (e.g : breast cancer patient) (Ulitsky and Shamir, 2008). This method required extensive samples of datasets with similar clinical criterias, unlike JAM and the two other approaches above which can use a single condition experiment. Another coexpressed-genes based approach developed by Guo et. al. used edge based scoring rather than vertex based scoring (Guo et al., 2007). In this case, a score on an edge represents the correlation in expression between a pair of nodes that share an edge. Such an edge based approach requires more extensive search than a vertex based approach, as the number of edges tend to exceed the number of vertices in a biological network. 53

5.2 Future Work

It is important to note that the pathway searching approach employed in this work and other similar work is constrained by the accuracy and completeness of the input network that is being searched. For this work, the accuracy of the KEGG network is critical since it forms the network that is searched. The drawback in using one source of input network is the potential for missing or incomplete interaction data. One possible improvement is to combine other interaction data from dierent interaction databases into the current input network. During the integration process, careful selection of interaction data is needed to get more accurate input to JAM search. Other obstacles, like the integration of dierent multiple node IDs will be faced by the integrator. One possible solution to this integration problem is to convert all node IDs from dierent databases into one approved ID. Having additional nodes and interaction data, brought in by expanding the input network, will possibly bring more signicant genes to the search results.

In this work, the rst suggested modication, randomizing the initial subnetworks list, was found to be ineective in score improvement. An alternative to consider is seeding the network search by starting with a list of known-to-be-signicant genes toggled on. Such an approach has the potential to discover higher-scoring subnetworks, as it ensures the initial placement of nodes is in the high scoring regions, and more importantly, can be used to allow analysis of the subnetwork driven by the target genes. While this seeding may cause a decrease in the freedom of exploration for the search, its potential benets support its evaluation against the current random seed approach.

The detection of consistent active subnetworks over multiple JAM results requires the determinination of how many times a node must show up in the JAM results to be considered signicant. Over the course of this work, the number of runs used was ten, while the cuto for signicant nodes was based on the signicance level of 0.05. It is worthwhile to observe the dynamics of the subnetwork result if the method employs these parameters dierently. If the cuto is being decreased, one possible scenario is an increasing number of low dierentially 54 expressed nodes, while also bringing in more signicant genes to the result. A technique such as ROC analysis will enable nding the appropriate equilibrium point for the cuto. This type of technique may also be useful in determining the number of subnetwork to maintain during the JAM search process (the parameter M described in Section 2.2). Such analysis requires some type of standard against which the result from using a particular parameter value will be compared. For any expression dataset, this standard can be dened by a signicant genes list (all genes with p-value below some threshold).

Finally, in this work, the JAM search method is separated from the statistical lter that work as a postprocessing method. For simplicity reasons, it would be useful to further automate the process by integrating the searching method and the statistical lter employed after the search. Bibliography

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Appendix A : Subnetwork Results

A.1 Subnetwork Result at 1hr Time Point

Genes Gene Name Gene Title SLR 80908 Abo ABO blood group (transferase A, alpha 1-3-N- -3.6 acetylgalactosaminyltransferase, transferase B, alpha 1-3- galactosyltransferase) 170758 Rac3 RAS-related C3 botulinum substrate 3 -3.6 114141 Cldn16 claudin 16 -3.1 11474 Actn3 actinin alpha 3 -3 18121 Nog noggin -2.9 22772 Zic2 zinc finger protein of the cerebellum 2 -2.7 109821 F11 coagulation factor XI -2.7 106648 Cyp4f15 cytochrome P450, family 4, subfamily f, polypeptide 15 -2.7 19274 Ptprm protein tyrosine phosphatase, receptor type, M -2.7 16398 Itga2 integrin alpha 2 -2.7 23920 Insrr insulin receptor-related receptor -2.6 216456 Gls2 glutaminase 2 (liver, mitochondrial) -2.5 226143 Cyp2c44 cytochrome P450, family 2, subfamily c, polypeptide 44 -2.5 19051 Gsbs G substrate -2.4 15450 Lipc lipase, hepatic -2.4 17885 Myh8 myosin, heavy polypeptide 8, skeletal muscle, perinatal -2.2 12292 Cacna1s calcium channel, voltage-dependent, L type, alpha 1S -2.1 subunit 13119 Cyp4a14 cytochrome P450, family 4, subfamily a, polypeptide 14 -2.1 53624 Cldn7 claudin 7 -2.1 11472 Actn2 actinin alpha 2 -2.1 19279 Ptprr protein tyrosine phosphatase, receptor type, R -2 20890 Wnt8a wingless-related MMTV integration site 8A -1.9 12740 Cldn4 claudin 4 -1.9 21809 Tgfb3 transforming growth factor, beta 3 -1.9 21390 Tbxa2r thromboxane A2 receptor -1.8 11687 Alox15 arachidonate 15-lipoxygenase -1.4 384783 Irs2 insulin receptor substrate 2 -1.2 14860 Gsta4 glutathione S-transferase, alpha 4 -1.1 109264 Me3 malic enzyme 3, NADP(+)-dependent, mitochondrial -1.1 12161 Bmp6 bone morphogenetic protein 6 -1.1 18430 Oxtr oxytocin receptor -1.1 13077 Cyp1a2 cytochrome P450, family 1, subfamily a, polypeptide 2 -0.9 22330 Vcl vinculin -0.2 12790 Cnga3 cyclic nucleotide gated channel alpha 3 0 12540 Cdc42 cell division cycle 42 homolog (S. cerevisiae) 0.1 60

Genes Gene Name Gene Title SLR 26398 Map2k4 mitogen-activated protein kinase kinase 4 0.1 55980 Impa1 inositol (myo)-1(or 4)-monophosphatase 1 0.3 12649 Chek1 checkpoint kinase 1 homolog (S. pombe) 0.3 18770 Pklr pyruvate kinase liver and red blood cell 0.4 12388 Ctnnd1 catenin (cadherin associated protein), delta 1 0.4 26409 Map3k7 mitogen-activated protein kinase kinase kinase 7 0.4 54131 Irf3 interferon regulatory factor 3 0.4 14343 Fut1 fucosyltransferase 1 0.5 21824 Thbd thrombomodulin 0.5 268977 Ltbp1 latent transforming growth factor beta binding protein 1 0.5 15251 Hif1a hypoxia inducible factor 1, alpha subunit 0.9 19012 Ppap2a phosphatidic acid phosphatase type 2A 1 11684 Alox12 arachidonate 12-lipoxygenase 1.1 230103 Npr2 natriuretic peptide receptor 2 1.1 67374 Jam2 junction adhesion molecule 2 1.1 14617 Gjd2 gap junction protein, delta 2 1.1 208665 Akr1d1 aldo-keto reductase family 1, member D1 1.1 20449 St8sia1 ST8 alpha-N-acetyl-neuraminide alpha-2,8- 1.1 sialyltransferase 1 23959 Nt5e 5' nucleotidase, ecto 1.2 54195 Gucy1b3 guanylate cyclase 1, soluble, beta 3 1.2 12804 Cntfr ciliary neurotrophic factor receptor 1.2 13088 Cyp2b10 cytochrome P450, family 2, subfamily b, polypeptide 10 1.3 14365 Fzd3 frizzled homolog 3 (Drosophila) 1.3 17884 Myh4 myosin, heavy polypeptide 4, skeletal muscle 1.3 12326 Camk4 calcium/calmodulin-dependent protein kinase IV 1.4 13078 Cyp1b1 cytochrome P450, family 1, subfamily b, polypeptide 1 1.4 71941 Cars2 cysteinyl-tRNA synthetase 2 (mitochondrial)(putative) 1.4 17906 Myl2 myosin, light polypeptide 2, regulatory, cardiac, slow 1.5 16159 Il12a interleukin 12a 1.5 56405 Dusp14 dual specificity phosphatase 14 1.6 15529 Sdc2 syndecan 2 1.6 12834 Col6a2 collagen, type VI, alpha 2 1.6 18595 Pdgfra platelet derived growth factor receptor, alpha polypeptide 1.7 217480 Dgkb diacylglycerol kinase, beta 1.8 14165 Fgf10 fibroblast growth factor 10 1.8 21828 Thbs4 thrombospondin 4 1.8 72930 Ppp2r2b protein phosphatase 2 (formerly 2A), regulatory subunit B 1.9 (PR 52), beta isoform 13617 Ednra endothelin receptor type A 1.9 12425 Cckar cholecystokinin A receptor 2 15562 Htr4 5 hydroxytryptamine (serotonin) receptor 4 2 22059 Trp53 transformation related protein 53 2 61

Genes Gene Name Gene Title SLR 14417 Gad2 glutamic acid decarboxylase 2 2.1 56717 Mtor mechanistic target of rapamycin (serine/threonine kinase) 2.1 12505 Cd44 CD44 antigen 2.1 229927 Clca4 chloride channel calcium activated 4 2.1 12293 Cacna2d1 calcium channel, voltage-dependent, alpha2/delta subunit 2.2 1 19225 Ptgs2 prostaglandin-endoperoxide synthase 2 2.2 23984 Pde10a phosphodiesterase 10A 2.2 80857 Fgf20 fibroblast growth factor 20 2.2 93742 Pard3 par-3 (partitioning defective 3) homolog (C. elegans) 2.2 15974 Ifnab interferon alpha B 2.2 242669 Adc arginine decarboxylase 2.2 19207 Ptch2 patched homolog 2 2.3 59001 Pole3 polymerase (DNA directed), epsilon 3 (p17 subunit) 2.3 20019 Polr1a polymerase (RNA) I polypeptide A 2.3 110279 Bcr breakpoint cluster region 2.3 14061 F2 coagulation factor II 2.3 13489 Drd2 dopamine receptor 2 2.3 13090 Cyp2b19 cytochrome P450, family 2, subfamily b, polypeptide 19 2.3 107589 Mylk myosin, light polypeptide kinase 2.3 19218 Ptger3 prostaglandin E receptor 3 (subtype EP3) 2.3 14633 Gli2 GLI-Kruppel family member GLI2 2.4 108105 B3gnt5 UDP-GlcNAc:betaGal beta-1,3-N- 2.4 acetylglucosaminyltransferase 5 21827 Thbs3 thrombospondin 3 2.4 26876 Adh4 alcohol dehydrogenase 4 (class II), pi polypeptide 2.4 12315 Calm3 calmodulin 3 2.5 17319 Mif macrophage migration inhibitory factor 2.5 69836 Pla2g12b phospholipase A2, group XIIB 2.5 76654 Upp2 uridine phosphorylase 2 2.5 110197 Dgkg diacylglycerol kinase, gamma 2.5 230379 Acer2 alkaline ceramidase 2 2.5 22612 Yes1 Yamaguchi sarcoma viral (v-yes) oncogene homolog 1 2.5 67071 Rps6ka6 ribosomal protein S6 kinase polypeptide 6 2.5 22045 Trhr thyrotropin releasing hormone receptor 2.5 13649 Egfr epidermal growth factor receptor 2.5 18578 Pde4b phosphodiesterase 4B, cAMP specific 2.6 11607 Agtr1a angiotensin II receptor, type 1a 2.6 56863 Cldn9 claudin 9 2.6 13637 Efna2 ephrin A2 2.7 11855 Arhgap5 Rho GTPase activating protein 5 2.7 192157 Socs7 suppressor of cytokine signaling 7 2.7 21415 Tcf7l1 transcription factor 7-like 1 (T-cell specific, HMG box) 2.7 62

Genes Gene Name Gene Title SLR 14183 Fgfr2 fibroblast growth factor receptor 2 2.7 22032 Traf4 TNF receptor associated factor 4 2.7 16842 Lef1 lymphoid enhancer binding factor 1 2.7 103583 Fbxw11 F-box and WD-40 domain protein 11 2.8 18534 Pck1 phosphoenolpyruvate carboxykinase 1, cytosolic 2.8 12503 Cd247 CD247 antigen 2.8 26877 B3galt1 UDP-Gal:betaGlcNAc beta 1,3-galactosyltransferase, 2.8 polypeptide 1 14538 Gcnt2 glucosaminyl (N-acetyl) transferase 2, I-branching 2.8 enzyme 15486 Hsd17b2 hydroxysteroid (17-beta) dehydrogenase 2 2.8 227231 Cps1 carbamoyl-phosphate synthetase 1 2.8 14451 Gas1 growth arrest specific 1 2.9 13874 Ereg epiregulin 2.9 19116 Prlr prolactin receptor 2.9 232493 Gys2 glycogen synthase 2 2.9 13109 Cyp2j5 cytochrome P450, family 2, subfamily j, polypeptide 5 2.9 13488 Drd1a dopamine receptor D1A 3 17879 Myh1 myosin, heavy polypeptide 1, skeletal muscle, adult 3 241226 Itga8 integrin alpha 8 3 15245 Hhip Hedgehog-interacting protein 3 22417 Wnt4 wingless-related MMTV integration site 4 3 13806 Eno1 enolase 1, alpha non-neuron 3.1 22637 Zap70 zeta-chain (TCR) associated protein kinase 3.1 13087 Cyp2a5 cytochrome P450, family 2, subfamily a, polypeptide 5 3.1 15965 Ifna2 interferon alpha 2 3.1 14368 Fzd6 frizzled homolog 6 (Drosophila) 3.1 12921 Crhr1 corticotropin releasing hormone receptor 1 3.1 433182 Gm5506 predicted gene 5506 3.1 56727 Miox myo-inositol oxygenase 3.1 13086 Cyp2a4 cytochrome P450, family 2, subfamily a, polypeptide 4 3.1 54611 Pde3a phosphodiesterase 3A, cGMP inhibited 3.2 26361 Avpr1b arginine vasopressin receptor 1B 3.2 70408 Polr3f polymerase (RNA) III (DNA directed) polypeptide F 3.2 56508 Rapgef4 Rap guanine nucleotide exchange factor (GEF) 4 3.3 234515 Inpp4b inositol polyphosphate-4-phosphatase, type II 3.3 13839 Epha5 Eph receptor A5 3.4 12912 Creb1 cAMP responsive element binding protein 1 3.4 19876 Robo1 roundabout homolog 1 (Drosophila) 3.4 286940 Flnb filamin, beta 3.4 23844 Clca3 chloride channel calcium activated 3 3.4 29859 Sult4a1 sulfotransferase family 4A, member 1 3.4 18802 Plcd4 phospholipase C, delta 4 3.4 63

Genes Gene Name Gene Title SLR 56615 Mgst1 microsomal glutathione S-transferase 1 3.5 19220 Ptgfr prostaglandin F receptor 3.5 74987 4930468A15Rik RIKEN cDNA 4930468A15 gene 3.5 16160 Il12b interleukin 12b 3.5 12722 Clca1 chloride channel calcium activated 1 3.5 269275 Acvr1c activin A receptor, type IC 3.5 19123 Proc protein C 3.5 80797 Clca2 chloride channel calcium activated 2 3.5 22341 Vegfc vascular endothelial growth factor C 3.5 14163 Fgd1 FYVE, RhoGEF and PH domain containing 1 3.6 16009 Igfbp3 insulin-like growth factor binding protein 3 3.6 237310 Il22ra2 interleukin 22 receptor, alpha 2 3.6 14634 Gli3 GLI-Kruppel family member GLI3 3.7 18212 Ntrk2 neurotrophic tyrosine kinase, receptor, type 2 3.7 58220 Pard6b par-6 (partitioning defective 6) homolog beta (C. elegans) 3.7 12843 Col1a2 collagen, type I, alpha 2 3.7 12832 Col5a2 collagen, type V, alpha 2 3.7 15977 Ifnb1 interferon beta 1, fibroblast 3.7 18119 Nodal nodal 3.7 18575 Pde1c phosphodiesterase 1C 3.8 18125 Nos1 nitric oxide synthase 1, neuronal 3.8 16412 Itgb1 integrin beta 1 (fibronectin receptor beta) 3.8 22171 Tyms thymidylate synthase 3.8 29863 Pde7b phosphodiesterase 7B 3.9 20671 Sox17 SRY-box containing gene 17 3.9 15967 Ifna4 interferon alpha 4 3.9 66513 Tab1 TGF-beta activated kinase 1/MAP3K7 binding protein 1 3.9 18705 Pik3c2g phosphatidylinositol 3-kinase, C2 domain containing, 3.9 gamma polypeptide 12532 Cdc25c cell division cycle 25 homolog C (S. pombe) 4 111507 Igh immunoglobulin heavy chain complex 4.1 58998 Pvrl3 poliovirus receptor-related 3 4.2 18414 Osmr oncostatin M receptor 4.3 14126 Ms4a2 membrane-spanning 4-domains, subfamily A, member 2 4.3 20411 Sorbs1 sorbin and SH3 domain containing 1 4.4 23956 Neu2 neuraminidase 2 4.4 18205 Ntf3 neurotrophin 3 4.5 22239 Ugt8a UDP galactosyltransferase 8A 4.6 15945 Cxcl10 chemokine (C-X-C motif) ligand 10 4.6 16428 Itk IL2-inducible T-cell kinase 4.7 18218 Dusp8 dual specificity phosphatase 8 4.7 19353 Rac1 RAS-related C3 botulinum substrate 1 4.9 64

Genes Gene Name Gene Title SLR 20724 Serpinb5 serine (or cysteine) peptidase inhibitor, clade B, member 5.3 5 11605 Gla galactosidase, alpha 5.4 16193 Il6 interleukin 6 5.5 65

A.2 Subnetwork Result at 3hr Time Point

Entrez ID Gene Name Gene Title SLR 18223 Numbl numb-like -3.8 337924 Cyp3a44 cytochrome P450, family 3, subfamily a, polypeptide 44 -3.6 13590 Lefty1 left right determination factor 1 -3.4 56811 Dkk2 dickkopf homolog 2 (Xenopus laevis) -3.4 68214 Gsto2 glutathione S-transferase omega 2 -3.3 101809 Spred3 sprouty-related, EVH1 domain containing 3 -3.2 384783 Irs2 insulin receptor substrate 2 -3.1 18121 Nog noggin -3.1 319713 Ablim3 actin binding LIM protein family, member 3 -2.9 21390 Tbxa2r thromboxane A2 receptor -2.8 50929 Il22 interleukin 22 -2.6 13107 Cyp2f2 cytochrome P450, family 2, subfamily f, polypeptide 2 -2.4 18160 Npr1 natriuretic peptide receptor 1 -2.4 11474 Actn3 actinin alpha 3 -2.3 14060 F13b coagulation factor XIII, beta subunit -2.3 56375 B4galt4 UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase, -1.9 polypeptide 4 93735 Wnt16 wingless-related MMTV integration site 16 -1.7 18979 Pon1 paraoxonase 1 -1.5 67112 Fgf22 fibroblast growth factor 22 -1.4 22436 Xdh xanthine dehydrogenase -1.2 12767 Cxcr4 chemokine (C-X-C motif) receptor 4 -1.1 21809 Tgfb3 transforming growth factor, beta 3 -0.5 16480 Jup junction plakoglobin -0.2 18770 Pklr pyruvate kinase liver and red blood cell 0.1 21823 Th tyrosine hydroxylase 0.9 16653 Kras v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 1.1 226413 Lct lactase 1.1 404549 Ifna14 interferon, alpha 14 1.2 19309 Pygm muscle glycogen phosphorylase 1.2 110197 Dgkg diacylglycerol kinase, gamma 1.4 53857 Tuba8 tubulin, alpha 8 1.4 18719 Pip5k1b phosphatidylinositol-4-phosphate 5-kinase, type 1 beta 1.5 12006 Axin2 axin2 1.6 18720 Pip5k1a phosphatidylinositol-4-phosphate 5-kinase, type 1 alpha 1.6 15566 Htr7 5-hydroxytryptamine (serotonin) receptor 7 1.6 18707 Pik3cd phosphatidylinositol 3-kinase catalytic delta polypeptide 1.7 75590 Dusp9 dual specificity phosphatase 9 1.7 21337 Tacr2 tachykinin receptor 2 1.7 246256 Fcgr4 Fc receptor, IgG, low affinity IV 1.8 237310 Il22ra2 interleukin 22 receptor, alpha 2 1.9 66

Entrez ID Gene Name Gene Title SLR 229927 Clca4 chloride channel calcium activated 4 2.2 14609 Gja1 gap junction protein, alpha 1 2.3 13163 Daxx Fas death domain-associated protein 2.3 29857 Mapk12 mitogen-activated protein kinase 12 2.3 56405 Dusp14 dual specificity phosphatase 14 2.3 17319 Mif macrophage migration inhibitory factor 2.3 14172 Fgf18 fibroblast growth factor 18 2.4 13840 Epha6 Eph receptor A6 2.4 13839 Epha5 Eph receptor A5 2.4 231327 Ppat phosphoribosyl pyrophosphate amidotransferase 2.4 12914 Crebbp CREB binding protein 2.5 12804 Cntfr ciliary neurotrophic factor receptor 2.5 19116 Prlr prolactin receptor 2.5 12293 Cacna2d1 calcium channel, voltage-dependent, alpha2/delta subunit 1 2.5 15051 H2-T9 histocompatibility 2, T region locus 9 2.5 15039 H2-T22 histocompatibility 2, T region locus 22 2.5 16410 Itgav integrin alpha V 2.5 77579 Myh10 myosin, heavy polypeptide 10, non-muscle 2.5 107589 Mylk myosin, light polypeptide kinase 2.5 18129 Notch2 Notch gene homolog 2 (Drosophila) 2.5 22045 Trhr thyrotropin releasing hormone receptor 2.5 12519 Cd80 CD80 antigen 2.5 72930 Ppp2r2b protein phosphatase 2 (formerly 2A), regulatory subunit B 2.5 (PR 52), beta isoform 13649 Egfr epidermal growth factor receptor 2.5 18595 Pdgfra platelet derived growth factor receptor, alpha polypeptide 2.5 19353 Rac1 RAS-related C3 botulinum substrate 1 2.6 20869 Stk11 serine/threonine kinase 11 2.6 12300 Cacng2 calcium channel, voltage-dependent, gamma subunit 2 2.6 14061 F2 coagulation factor II 2.6 18948 Pnmt phenylethanolamine-N-methyltransferase 2.6 12411 Cbs cystathionine beta-synthase 2.6 13617 Ednra endothelin receptor type A 2.6 56615 Mgst1 microsomal glutathione S-transferase 1 2.7 22171 Tyms thymidylate synthase 2.7 64337 Gng13 guanine nucleotide binding protein (G protein), gamma 13 2.7 19417 Rasgrf1 RAS protein-specific guanine nucleotide-releasing factor 1 2.7 13087 Cyp2a5 cytochrome P450, family 2, subfamily a, polypeptide 5 2.7 13086 Cyp2a4 cytochrome P450, family 2, subfamily a, polypeptide 4 2.7 235320 Zbtb16 zinc finger and BTB domain containing 16 2.7 22417 Wnt4 wingless-related MMTV integration site 4 2.7 22145 Tuba4a tubulin, alpha 4A 2.8 433182 Gm5506 predicted gene 5506 2.8 67

Entrez ID Gene Name Gene Title SLR 13806 Eno1 enolase 1, alpha non-neuron 2.8 12427 Ccna1 cyclin A1 2.8 12649 Chek1 checkpoint kinase 1 homolog (S. pombe) 2.8 209200 Dtx3l deltex 3-like (Drosophila) 2.8 11540 Adora2a adenosine A2a receptor 2.8 54611 Pde3a phosphodiesterase 3A, cGMP inhibited 2.8 18260 Ocln occludin 2.9 18534 Pck1 phosphoenolpyruvate carboxykinase 1, cytosolic 2.9 14171 Fgf17 fibroblast growth factor 17 2.9 111507 Igh immunoglobulin heavy chain complex 2.9 231691 Sds serine dehydratase 2.9 140781 Myh7 myosin, heavy polypeptide 7, cardiac muscle, beta 2.9 268977 Ltbp1 latent transforming growth factor beta binding protein 1 2.9 15245 Hhip Hedgehog-interacting protein 2.9 18131 Notch3 Notch gene homolog 3 (Drosophila) 2.9 54167 Icos inducible T-cell co-stimulator 3 24117 Wif1 Wnt inhibitory factor 1 3 18802 Plcd4 phospholipase C, delta 4 3 70408 Polr3f polymerase (RNA) III (DNA directed) polypeptide F 3 15967 Ifna4 interferon alpha 4 3 268860 Abat 4-aminobutyrate aminotransferase 3 269275 Acvr1c activin A receptor, type IC 3 241656 Pak7 p21 protein (Cdc42/Rac)-activated kinase 7 3 14812 Grin2b glutamate receptor, ionotropic, NMDA2B (epsilon 2) 3 15007 H2-Q10 histocompatibility 2, Q region locus 10 3 12703 Socs1 suppressor of cytokine signaling 1 3 338403 Cndp1 carnosine dipeptidase 1 (metallopeptidase M20 family) 3 14811 Grin2a glutamate receptor, ionotropic, NMDA2A (epsilon 1) 3.1 108105 B3gnt5 UDP-GlcNAc:betaGal beta-1,3-N- 3.1 acetylglucosaminyltransferase 5 103583 Fbxw11 F-box and WD-40 domain protein 11 3.1 17884 Myh4 myosin, heavy polypeptide 4, skeletal muscle 3.1 14924 Magi1 membrane associated guanylate kinase, WW and PDZ 3.2 domain containing 1 20847 Stat2 signal transducer and activator of transcription 2 3.2 14183 Fgfr2 fibroblast growth factor receptor 2 3.2 14161 Fga fibrinogen alpha chain 3.2 74167 Nudt9 nudix (nucleoside diphosphate linked moiety X)-type motif 9 3.2 20315 Cxcl12 chemokine (C-X-C motif) ligand 12 3.2 15486 Hsd17b2 hydroxysteroid (17-beta) dehydrogenase 2 3.2 13166 Dbh dopamine beta hydroxylase 3.2 18778 Pla2g1b phospholipase A2, group IB, pancreas 3.2 14451 Gas1 growth arrest specific 1 3.2 68

Entrez ID Gene Name Gene Title SLR 13098 Cyp2c39 cytochrome P450, family 2, subfamily c, polypeptide 39 3.3 19225 Ptgs2 prostaglandin-endoperoxide synthase 2 3.3 227613 Tubb2c tubulin, beta 2C 3.3 22341 Vegfc vascular endothelial growth factor C 3.3 621968 Gm6273 predicted gene 6273 3.3 234724 Tat tyrosine aminotransferase 3.3 19017 Ppargc1a peroxisome proliferative activated receptor, gamma, 3.3 coactivator 1 alpha 108071 Grm5 glutamate receptor, metabotropic 5 3.3 17769 Mthfr 5,10-methylenetetrahydrofolate reductase 3.3 140491 Ppp1r3a protein phosphatase 1, regulatory (inhibitor) subunit 3A 3.4 320202 Lefty2 left-right determination factor 2 3.4 29863 Pde7b phosphodiesterase 7B 3.4 13078 Cyp1b1 cytochrome P450, family 1, subfamily b, polypeptide 1 3.5 14964 H2-D1 histocompatibility 2, D region locus 1 3.5 547348 H2-T3-like MHC class I antigen 3.5 93742 Pard3 par-3 (partitioning defective 3) homolog (C. elegans) 3.5 20617 Snca synuclein, alpha 3.5 14538 Gcnt2 glucosaminyl (N-acetyl) transferase 2, I-branching enzyme 3.5 14634 Gli3 GLI-Kruppel family member GLI3 3.5 234515 Inpp4b inositol polyphosphate-4-phosphatase, type II 3.5 23984 Pde10a phosphodiesterase 10A 3.5 114715 Spred1 sprouty protein with EVH-1 domain 1, related sequence 3.5 15043 H2-T3 histocompatibility 2, T region locus 3 3.5 15564 Htr5b 5-hydroxytryptamine (serotonin) receptor 5B 3.6 56066 Cxcl11 chemokine (C-X-C motif) ligand 11 3.6 16412 Itgb1 integrin beta 1 (fibronectin receptor beta) 3.6 54123 Irf7 interferon regulatory factor 7 3.6 15977 Ifnb1 interferon beta 1, fibroblast 3.6 22035 Tnfsf10 tumor necrosis factor (ligand) superfamily, member 10 3.7 22637 Zap70 zeta-chain (TCR) associated protein kinase 3.7 12503 Cd247 CD247 antigen 3.7 17888 Myh6 myosin, heavy polypeptide 6, cardiac muscle, alpha 3.7 56508 Rapgef4 Rap guanine nucleotide exchange factor (GEF) 4 3.7 13489 Drd2 dopamine receptor 2 3.7 58220 Pard6b par-6 (partitioning defective 6) homolog beta (C. elegans) 3.8 23844 Clca3 chloride channel calcium activated 3 3.8 15492 Hsd3b1 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid 3.8 delta-isomerase 1 14177 Fgf6 fibroblast growth factor 6 3.9 16160 Il12b interleukin 12b 3.9 20846 Stat1 signal transducer and activator of transcription 1 4.1 69

Entrez ID Gene Name Gene Title SLR 12395 Runx1t1 runt-related transcription factor 1; translocated to, 1 (cyclin 4.1 D-related) 20888 Sult1c1 sulfotransferase family, cytosolic, 1C, member 1 4.2 18218 Dusp8 dual specificity phosphatase 8 4.3 12156 Bmp2 bone morphogenetic protein 2 4.4 12532 Cdc25c cell division cycle 25 homolog C (S. pombe) 4.5 12722 Clca1 chloride channel calcium activated 1 4.6 80797 Clca2 chloride channel calcium activated 2 4.6 15378 Hnf4a hepatic nuclear factor 4, alpha 4.7 11607 Agtr1a angiotensin II receptor, type 1a 5.1 18414 Osmr oncostatin M receptor 5.1 16193 Il6 interleukin 6 5.9 17329 Cxcl9 chemokine (C-X-C motif) ligand 9 6.5 15945 Cxcl10 chemokine (C-X-C motif) ligand 10 7.7 70

A.3 Subnetwork Result at 6hr Time Point

Genes Gene Name Gene Title SLR 11554 Adrb1 adrenergic receptor, beta 1 -3.7 11450 Adipoq adiponectin, C1Q and collagen domain containing -3.7 13590 Lefty1 left right determination factor 1 -3.6 50929 Il22 interleukin 22 -3.2 58181 Il20 interleukin 20 -3.2 13857 Epor erythropoietin receptor -3.1 67486 Polr3g polymerase (RNA) III (DNA directed) polypeptide G -3.1 11472 Actn2 actinin alpha 2 -2.8 11474 Actn3 actinin alpha 3 -2.8 114141 Cldn16 claudin 16 -2.8 234889 Gucy1a2 guanylate cyclase 1, soluble, alpha 2 -2.8 238871 Pde4d phosphodiesterase 4D, cAMP specific -2.8 15978 Ifng interferon gamma -2.7 237313 Il20ra interleukin 20 receptor, alpha -1.2 228966 Ppp1r3d protein phosphatase 1, regulatory subunit 3D -1.2 233649 Cnga4 cyclic nucleotide gated channel alpha 4 -1 54131 Irf3 interferon regulatory factor 3 -0.1 21872 Tjp1 tight junction protein 1 0.6 17342 Mitf microphthalmia-associated transcription factor 0.7 21356 Tapbp TAP binding protein 1.1 108058 Camk2d calcium/calmodulin-dependent protein kinase II, delta 1.2 20779 Src Rous sarcoma oncogene 1.3 380928 Lmo7 LIM domain only 7 1.3 15566 Htr7 5-hydroxytryptamine (serotonin) receptor 7 1.5 20377 Sfrp1 secreted frizzled-related protein 1 1.5 19204 Ptafr platelet-activating factor receptor 1.6 11512 Adcy6 adenylate cyclase 6 1.7 13178 Dck deoxycytidine kinase 1.7 12367 Casp3 caspase 3 1.8 20971 Sdc4 syndecan 4 1.9 12505 Cd44 CD44 antigen 1.9 15564 Htr5b 5-hydroxytryptamine (serotonin) receptor 5B 2.5 237310 Il22ra2 interleukin 22 receptor, alpha 2 2.5 23844 Clca3 chloride channel calcium activated 3 2.7 14867 Gstm6 glutathione S-transferase, mu 6 2.7 13835 Epha1 Eph receptor A1 2.7 110197 Dgkg diacylglycerol kinase, gamma 2.8 14368 Fzd6 frizzled homolog 6 (Drosophila) 2.8 16842 Lef1 lymphoid enhancer binding factor 1 2.8 12444 Ccnd2 cyclin D2 2.8 71

Genes Gene Name Gene Title SLR 16818 Lck lymphocyte protein tyrosine kinase 2.8 21354 Tap1 transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) 2.8 13206 Ddx4 DEAD (Asp-Glu-Ala-Asp) box polypeptide 4 2.8 13840 Epha6 Eph receptor A6 2.8 17898 Myl7 myosin, light polypeptide 7, regulatory 2.8 16867 Lhcgr luteinizing hormone/choriogonadotropin receptor 2.8 26419 Mapk8 mitogen-activated protein kinase 8 2.8 12503 Cd247 CD247 antigen 2.8 22341 Vegfc vascular endothelial growth factor C 2.9 16334 Ins2 insulin II 2.9 93672 Il24 interleukin 24 2.9 16428 Itk IL2-inducible T-cell kinase 2.9 15495 Hsd3b4 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid 2.9 delta-isomerase 4 19085 Prkar1b protein kinase, cAMP dependent regulatory, type I beta 2.9 20655 Sod1 superoxide dismutase 1, soluble 2.9 13163 Daxx Fas death domain-associated protein 2.9 140491 Ppp1r3a protein phosphatase 1, regulatory (inhibitor) subunit 3A 2.9 57265 Fzd2 frizzled homolog 2 (Drosophila) 3 11540 Adora2a adenosine A2a receptor 3 14681 Gnao1 guanine nucleotide binding protein, alpha O 3 14183 Fgfr2 fibroblast growth factor receptor 2 3 19417 Rasgrf1 RAS protein-specific guanine nucleotide-releasing factor 1 3 22238 Ugt2b5 UDP glucuronosyltransferase 2 family, polypeptide B5 3 20019 Polr1a polymerase (RNA) I polypeptide A 3 12921 Crhr1 corticotropin releasing hormone receptor 1 3 75560 Ep400 E1A binding protein p400 3 16420 Itgb6 integrin beta 6 3.1 12293 Cacna2d1 calcium channel, voltage-dependent, alpha2/delta subunit 1 3.1 18578 Pde4b phosphodiesterase 4B, cAMP specific 3.1 14811 Grin2a glutamate receptor, ionotropic, NMDA2A (epsilon 1) 3.2 108083 Pip4k2b phosphatidylinositol-5-phosphate 4-kinase, type II, beta 3.2 16159 Il12a interleukin 12a 3.2 93685 Entpd7 ectonucleoside triphosphate diphosphohydrolase 7 3.2 246256 Fcgr4 Fc receptor, IgG, low affinity IV 3.2 14175 Fgf4 fibroblast growth factor 4 3.3 12519 Cd80 CD80 antigen 3.3 53972 Ngef neuronal guanine nucleotide exchange factor 3.3 12364 Casp12 caspase 12 3.3 14165 Fgf10 fibroblast growth factor 10 3.4 19353 Rac1 RAS-related C3 botulinum substrate 1 3.4 22423 Wnt8b wingless related MMTV integration site 8b 3.4 22413 Wnt2 wingless-related MMTV integration site 2 3.4 72

Genes Gene Name Gene Title SLR 12703 Socs1 suppressor of cytokine signaling 1 3.4 18260 Ocln occludin 3.5 18802 Plcd4 phospholipase C, delta 4 3.5 15039 H2-T22 histocompatibility 2, T region locus 22 3.5 15051 H2-T9 histocompatibility 2, T region locus 9 3.5 15024 H2-T10 histocompatibility 2, T region locus 10 3.5 23956 Neu2 neuraminidase 2 3.5 22059 Trp53 transformation related protein 53 3.5 21828 Thbs4 thrombospondin 4 3.5 13043 Cttn cortactin 3.5 20511 Slc1a2 solute carrier family 1 (glial high affinity glutamate transporter), 3.6 member 2 13637 Efna2 ephrin A2 3.6 16169 Il15ra interleukin 15 receptor, alpha chain 3.6 56508 Rapgef4 Rap guanine nucleotide exchange factor (GEF) 4 3.6 22417 Wnt4 wingless-related MMTV integration site 4 3.6 18125 Nos1 nitric oxide synthase 1, neuronal 3.7 76654 Upp2 uridine phosphorylase 2 3.7 70789 Kynu kynureninase (L-kynurenine hydrolase) 3.7 19220 Ptgfr prostaglandin F receptor 3.7 11608 Agtr1b angiotensin II receptor, type 1b 3.8 621968 Gm6273 predicted gene 6273 3.8 14125 Fcer1a Fc receptor, IgE, high affinity I, alpha polypeptide 3.9 12843 Col1a2 collagen, type I, alpha 2 3.9 20846 Stat1 signal transducer and activator of transcription 1 3.9 14186 Fgfr4 fibroblast growth factor receptor 4 4 20847 Stat2 signal transducer and activator of transcription 2 4 12298 Cacnb4 calcium channel, voltage-dependent, beta 4 subunit 4 22178 Tyrp1 tyrosinase-related protein 1 4.1 13078 Cyp1b1 cytochrome P450, family 1, subfamily b, polypeptide 1 4.1 16412 Itgb1 integrin beta 1 (fibronectin receptor beta) 4.1 20849 Stat4 signal transducer and activator of transcription 4 4.1 17769 Mthfr 5,10-methylenetetrahydrofolate reductase 4.2 22239 Ugt8a UDP galactosyltransferase 8A 4.2 12156 Bmp2 bone morphogenetic protein 2 4.3 16160 Il12b interleukin 12b 4.3 13070 Cyp11a1 cytochrome P450, family 11, subfamily a, polypeptide 1 4.4 15969 Ifna6 interferon alpha 6 4.5 242519 Ifna12 interferon alpha 12 4.5 15972 Ifna9 interferon alpha 9 4.5 242517 Gm12597 predicted gene 12597 4.5 58998 Pvrl3 poliovirus receptor-related 3 4.5 15962 Ifna1 interferon alpha 1 4.5 73

Genes Gene Name Gene Title SLR 15970 Ifna7 interferon alpha 7 4.5 230396 Ifna13 interferon alpha 13 4.5 15974 Ifnab interferon alpha B 4.5 19225 Ptgs2 prostaglandin-endoperoxide synthase 2 4.7 15968 Ifna5 interferon alpha 5 4.7 21939 Cd40 CD40 antigen 4.7 15186 Hdc histidine decarboxylase 4.8 56066 Cxcl11 chemokine (C-X-C motif) ligand 11 4.9 18126 Nos2 nitric oxide synthase 2, inducible 5 71586 Ifih1 interferon induced with helicase C domain 1 5 111507 Igh immunoglobulin heavy chain complex 5 29863 Pde7b phosphodiesterase 7B 5 54123 Irf7 interferon regulatory factor 7 5.1 16641 Klrc1 killer cell lectin-like receptor subfamily C, member 1 5.1 22035 Tnfsf10 tumor necrosis factor (ligand) superfamily, member 10 5.2 12296 Cacnb2 calcium channel, voltage-dependent, beta 2 subunit 5.4 22045 Trhr thyrotropin releasing hormone receptor 5.6 16193 Il6 interleukin 6 6.7 15977 Ifnb1 interferon beta 1, fibroblast 7.1 17329 Cxcl9 chemokine (C-X-C motif) ligand 9 7.4 15967 Ifna4 interferon alpha 4 7.8 15965 Ifna2 interferon alpha 2 7.9 15945 Cxcl10 chemokine (C-X-C motif) ligand 10 8 74

A.4 Subnetwork Result at 12hr Time Point

Entrez ID Gene Name Gene Title SLR 67486 Polr3g polymerase (RNA) III (DNA directed) polypeptide G -4.9 212679 Mars2 methionine-tRNA synthetase 2 (mitochondrial) -4.7 243548 Prickle2 prickle homolog 2 (Drosophila) -4.5 21877 Tk1 thymidine kinase 1 -4.3 234889 Gucy1a2 guanylate cyclase 1, soluble, alpha 2 -3.7 13590 Lefty1 left right determination factor 1 -3.7 384783 Irs2 insulin receptor substrate 2 -3.6 94215 Ugt2a1 UDP glucuronosyltransferase 2 family, polypeptide A1 -3.6 552899 Ugt2a2 UDP glucuronosyltransferase 2 family, polypeptide A2 -3.6 11540 Adora2a adenosine A2a receptor 3.1 12703 Socs1 suppressor of cytokine signaling 1 3.3 57260 Ltb4r2 leukotriene B4 receptor 2 3.3 12524 Cd86 CD86 antigen 3.3 14964 H2-D1 histocompatibility 2, D region locus 1 3.4 22171 Tyms thymidylate synthase 3.4 14583 Gfpt1 glutamine fructose-6-phosphate transaminase 1 3.5 22417 Wnt4 wingless-related MMTV integration site 4 3.5 15962 Ifna1 interferon alpha 1 3.5 15970 Ifna7 interferon alpha 7 3.5 242517 Gm12597 predicted gene 12597 3.5 230396 Ifna13 interferon alpha 13 3.5 15969 Ifna6 interferon alpha 6 3.5 242519 Ifna12 interferon alpha 12 3.5 15974 Ifnab interferon alpha B 3.5 12477 Ctla4 cytotoxic T-lymphocyte-associated protein 4 3.5 11605 Gla galactosidase, alpha 3.5 16542 Kdr kinase insert domain protein receptor 3.5 11674 Aldoa aldolase A, fructose-bisphosphate 3.6 26361 Avpr1b arginine vasopressin receptor 1B 3.6 234724 Tat tyrosine aminotransferase 3.6 14165 Fgf10 fibroblast growth factor 10 3.7 18129 Notch2 Notch gene homolog 2 (Drosophila) 3.7 192157 Socs7 suppressor of cytokine signaling 7 3.8 14871 Gstt1 glutathione S-transferase, theta 1 3.8 54611 Pde3a phosphodiesterase 3A, cGMP inhibited 3.8 12921 Crhr1 corticotropin releasing hormone receptor 1 3.8 20846 Stat1 signal transducer and activator of transcription 1 3.9 20847 Stat2 signal transducer and activator of transcription 2 4 56615 Mgst1 microsomal glutathione S-transferase 1 4 24117 Wif1 Wnt inhibitory factor 1 4 75

Entrez ID Gene Name Gene Title SLR 16159 Il12a interleukin 12a 4 67374 Jam2 junction adhesion molecule 2 4 50780 Rgs3 regulator of G-protein signaling 3 4 16169 Il15ra interleukin 15 receptor, alpha chain 4.1 12315 Calm3 calmodulin 3 4.1 16428 Itk IL2-inducible T-cell kinase 4.2 76654 Upp2 uridine phosphorylase 2 4.2 15051 H2-T9 histocompatibility 2, T region locus 9 4.4 15039 H2-T22 histocompatibility 2, T region locus 22 4.4 15024 H2-T10 histocompatibility 2, T region locus 10 4.4 14675 Gna14 guanine nucleotide binding protein, alpha 14 4.4 320202 Lefty2 left-right determination factor 2 4.4 12296 Cacnb2 calcium channel, voltage-dependent, beta 2 subunit 4.5 70789 Kynu kynureninase (L-kynurenine hydrolase) 4.6 13078 Cyp1b1 cytochrome P450, family 1, subfamily b, polypeptide 1 4.7 15968 Ifna5 interferon alpha 5 4.7 16641 Klrc1 killer cell lectin-like receptor subfamily C, member 1 4.8 12156 Bmp2 bone morphogenetic protein 2 4.9 23984 Pde10a phosphodiesterase 10A 5.1 22045 Trhr thyrotropin releasing hormone receptor 5.2 17769 Mthfr 5,10-methylenetetrahydrofolate reductase 5.3 12298 Cacnb4 calcium channel, voltage-dependent, beta 4 subunit 5.4 269275 Acvr1c activin A receptor, type IC 5.5 29863 Pde7b phosphodiesterase 7B 5.6 15186 Hdc histidine decarboxylase 5.6 16160 Il12b interleukin 12b 5.7 15967 Ifna4 interferon alpha 4 5.9 15965 Ifna2 interferon alpha 2 5.9 20849 Stat4 signal transducer and activator of transcription 4 5.9 15972 Ifna9 interferon alpha 9 6 54123 Irf7 interferon regulatory factor 7 6 56066 Cxcl11 chemokine (C-X-C motif) ligand 11 6.2 19225 Ptgs2 prostaglandin-endoperoxide synthase 2 6.3 22035 Tnfsf10 tumor necrosis factor (ligand) superfamily, member 10 6.7 16193 Il6 interleukin 6 7.1 15977 Ifnb1 interferon beta 1, fibroblast 7.3 18126 Nos2 nitric oxide synthase 2, inducible 7.9 17329 Cxcl9 chemokine (C-X-C motif) ligand 9 7.9 15945 Cxcl10 chemokine (C-X-C motif) ligand 10 8.2 76

A.5 Subnetwork Result at 24hr Time Point

Entrez ID Gene Name Gene Title SLR 21877 Tk1 thymidine kinase 1 -5.3 18973 Pole polymerase (DNA directed), epsilon -5.2 67486 Polr3g polymerase (RNA) III (DNA directed) polypeptide G -4.2 234889 Gucy1a2 guanylate cyclase 1, soluble, alpha 2 -4 107869 Cth cystathionase (cystathionine gamma-lyase) -3.9 105349 Akr1c18 aldo-keto reductase family 1, member C18 -3.7 13590 Lefty1 left right determination factor 1 -3.7 12161 Bmp6 bone morphogenetic protein 6 -3.6 20302 Ccl3 chemokine (C-C motif) ligand 3 -3.6 15487 Hsd17b3 hydroxysteroid (17-beta) dehydrogenase 3 -3.5 67092 Gatm glycine amidinotransferase (L-arginine:glycine -3.4 amidinotransferase) 337924 Cyp3a44 cytochrome P450, family 3, subfamily a, polypeptide 44 -3.3 20810 Srm spermidine synthase -3.2 14268 Fn1 fibronectin 1 -3.2 552899 Ugt2a2 UDP glucuronosyltransferase 2 family, polypeptide A2 -3.2 13117 Cyp4a10 cytochrome P450, family 4, subfamily a, polypeptide 10 -3.2 94215 Ugt2a1 UDP glucuronosyltransferase 2 family, polypeptide A1 -3.2 11687 Alox15 arachidonate 15-lipoxygenase -3.1 11472 Actn2 actinin alpha 2 -3 20135 Rrm2 ribonucleotide reductase M2 -3 70750 Kdsr 3-ketodihydrosphingosine reductase -1.3 14718 Got1 glutamate oxaloacetate transaminase 1, soluble 1.3 213435 Mylk3 myosin light chain kinase 3 1.3 15976 Ifnar2 interferon (alpha and beta) receptor 2 1.4 17762 Mapt microtubule-associated protein tau 1.4 14633 Gli2 GLI-Kruppel family member GLI2 1.6 269275 Acvr1c activin A receptor, type IC 2.3 17974 Nck2 non-catalytic region of tyrosine kinase adaptor protein 2 2.8 15964 Ifna11 interferon alpha 11 3 22417 Wnt4 wingless-related MMTV integration site 4 3 16193 Il6 interleukin 6 3 18131 Notch3 Notch gene homolog 3 (Drosophila) 3.1 14600 Ghr growth hormone receptor 3.1 77974 Rdh12 retinol dehydrogenase 12 3.1 15042 H2-T24 histocompatibility 2, T region locus 24 3.1 103583 Fbxw11 F-box and WD-40 domain protein 11 3.2 12315 Calm3 calmodulin 3 3.2 268782 Agxt2 alanine-glyoxylate aminotransferase 2 3.2 17319 Mif macrophage migration inhibitory factor 3.2 19220 Ptgfr prostaglandin F receptor 3.3 77

Entrez ID Gene Name Gene Title SLR 20019 Polr1a polymerase (RNA) I polypeptide A 3.3 18802 Plcd4 phospholipase C, delta 4 3.3 234515 Inpp4b inositol polyphosphate-4-phosphatase, type II 3.3 11605 Gla galactosidase, alpha 3.4 16160 Il12b interleukin 12b 3.5 12322 Camk2a calcium/calmodulin-dependent protein kinase II alpha 3.5 547348 H2-T3-like MHC class I antigen 3.5 15043 H2-T3 histocompatibility 2, T region locus 3 3.5 14964 H2-D1 histocompatibility 2, D region locus 1 3.5 15018 H2-Q7 histocompatibility 2, Q region locus 7 3.6 14924 Magi1 membrane associated guanylate kinase, WW and PDZ 3.7 domain containing 1 26361 Avpr1b arginine vasopressin receptor 1B 3.7 83553 Tktl1 transketolase-like 1 3.7 237310 Il22ra2 interleukin 22 receptor, alpha 2 3.7 12843 Col1a2 collagen, type I, alpha 2 3.8 15051 H2-T9 histocompatibility 2, T region locus 9 3.8 15039 H2-T22 histocompatibility 2, T region locus 22 3.8 15559 Htr2b 5-hydroxytryptamine (serotonin) receptor 2B 3.8 103149 Upb1 ureidopropionase, beta 3.8 15024 H2-T10 histocompatibility 2, T region locus 10 3.8 21828 Thbs4 thrombospondin 4 3.9 14972 H2-K1 histocompatibility 2, K1, K region 3.9 241656 Pak7 p21 protein (Cdc42/Rac)-activated kinase 7 3.9 16420 Itgb6 integrin beta 6 3.9 15486 Hsd17b2 hydroxysteroid (17-beta) dehydrogenase 2 3.9 16641 Klrc1 killer cell lectin-like receptor subfamily C, member 1 3.9 18778 Pla2g1b phospholipase A2, group IB, pancreas 3.9 20846 Stat1 signal transducer and activator of transcription 1 4 16542 Kdr kinase insert domain protein receptor 4 14858 Gsta2 glutathione S-transferase, alpha 2 (Yc2) 4 22045 Trhr thyrotropin releasing hormone receptor 4.1 108071 Grm5 glutamate receptor, metabotropic 5 4.1 23984 Pde10a phosphodiesterase 10A 4.1 15019 H2-Q8 histocompatibility 2, Q region locus 8 4.1 13078 Cyp1b1 cytochrome P450, family 1, subfamily b, polypeptide 1 4.1 268977 Ltbp1 latent transforming growth factor beta binding protein 1 4.2 18129 Notch2 Notch gene homolog 2 (Drosophila) 4.3 15186 Hdc histidine decarboxylase 4.4 12296 Cacnb2 calcium channel, voltage-dependent, beta 2 subunit 4.4 20847 Stat2 signal transducer and activator of transcription 2 4.5 19268 Ptprf protein tyrosine phosphatase, receptor type, F 4.5 29863 Pde7b phosphodiesterase 7B 4.7 78

Entrez ID Gene Name Gene Title SLR 12814 Col11a1 collagen, type XI, alpha 1 4.7 17769 Mthfr 5,10-methylenetetrahydrofolate reductase 4.9 110557 H2-Q6 histocompatibility 2, Q region locus 6 5.1 15006 H2-Q1 histocompatibility 2, Q region locus 1 5.1 11674 Aldoa aldolase A, fructose-bisphosphate 5.2 22035 Tnfsf10 tumor necrosis factor (ligand) superfamily, member 10 5.5 54123 Irf7 interferon regulatory factor 7 6.4 12298 Cacnb4 calcium channel, voltage-dependent, beta 4 subunit 6.5 18126 Nos2 nitric oxide synthase 2, inducible 6.8 20849 Stat4 signal transducer and activator of transcription 4 7.5 79

Appendix B: Expression Data for Test Networks

B.1 Galactose Utilization Pathway

Gene ID Expression value p-value YLR264W -0.17 0.21059 YBR072W -0.447 3.35E-11 YMR183C -0.825 1.03E-16 YEL009C -0.031 0.55639 YGR218W -0.018 0.80969 YNL199C 0.433 5.65E-05 YBR093C -0.543 3.62E-13 YMR044W 0.357 8.82E-04 YEL015W 0.275 0.032829 YNL312W -0.121 0.24786 YGR203W -0.34 0.22451 YDR103W 0.023 0.92304 YDR311W 0.332 0.0087786 YDR174W -0.356 3.47E-08 YOR355W 0.43 0.0062666 YDR429C 0.354 1.66E-05 YJL203W 0.401 0.0046881 YHR171W 0.034 0.7782 YOR204W -0.91 8.35E-16 YDL023C -0.406 1.71E-08 YKR097W 0.123 0.13819 YOL058W -0.815 5.94E-10 YMR138W 0.221 0.12805 YBL069W -0.026 0.87354 YPL131W -0.246 1.48E-04 YNR050C 0.647 1.18E-07 YOL156W 0.105 0.28091 YGL161C -0.164 0.0065587 YHR084W 0.057 0.65365 YBR274W -0.052 0.55148 YPR010C -0.359 0.0061199 YDR100W -0.415 5.79E-10 YNL307C -0.063 0.37572 YOR089C 0.378 8.22E-06 YMR255W 0.397 0.0029074 YKL001C 0.683 2.71E-07 YDR244W 0.483 4.31E-04 YHR115C 0.138 0.079261 80

Gene ID Expression value p-value YLR075W -0.002 0.9794 YMR021C 0.066 0.54119 YHR055C 0.802 1.97E-12 YFL017C 0.124 0.050323 YHR005C 0.33 0.0031233 YLR116W 0.101 0.35769 YLR249W -0.769 0.035939 YOR120W 0.576 6.39E-09 YOR362C 0.225 0.0013356 YBR109C -0.163 0.0092082 YIL105C 0.197 0.016148 YPR062W -0.071 0.26496 YGR046W 0.124 0.10073 YDL013W 0.593 2.08E-05 YER062C 0.359 5.86E-06 YIL052C -0.025 0.66627 YLR175W 0.498 1.41E-07 YDR050C -0.728 8.67E-12 YDR171W -0.723 1.43E-12 YBR155W 0.519 3.71E-04 YFL039C -0.527 6.06E-12 YPR167C 0.708 5.31E-04 YCL032W 0.284 0.015244 YBR020W 2.939 2.81E-18 YIL160C 0.92 6.08E-07 YER116C 0.182 0.13915 YEL041W -0.265 0.035715 YNL311C -0.169 0.12031 YIL045W -0.134 0.072301 YCL030C 0.29 0.0016438 YFL038C 0.12 0.073548 YDR382W -0.314 1.42E-07 YER143W 0.179 0.018361 YAL038W -0.453 1.55E-07 YDR146C -0.027 0.76249 YNL113W 0.789 0.0028937 YKL204W 0.16 0.091109 YPR124W -0.462 8.38E-06 YER056CA null null YJL089W 0.442 0.033306 YKL012W 0.561 8.72E-05 YPL111W 0.957 5.24E-11 81

Gene ID Expression value p-value YNL116W 0.358 2.77E-04 YPL248C -0.211 0.088214 YOR167C -0.243 4.86E-05 YGR254W -0.171 0.025056 YLR321C 0.427 0.0047054 YNL189W -0.573 1.41E-08 YMR117C -0.296 0.35411 YPR110C -0.026 0.70564 YDL113C 0.304 0.0063436 YOR327C 0.559 4.48E-05 YDR277C 0.448 5.73E-04 YGL106W -0.059 0.29618 YLR310C -0.071 0.25519 YNL050C 0.594 7.51E-04 YBL005W 0 0.999999 YIL133C -0.146 0.012589 YHR135C 0.119 0.037227 YOL051W 0.111 0.30922 YER110C 0.43 3.63E-07 YGR014W -0.171 0.031836 YOR303W 0.403 1.59E-04 YGR019W -0.258 6.22E-05 YPL201C 0.597 0.0043411 YLR109W -0.486 2.34E-11 YOR212W -0.158 0.023184 YKR099W 1.101 6.99E-04 YLR284C 0.716 3.92E-04 YNL047C 0.029 0.7773 YER179W -0.167 0.13801 YFR014C 0.047 0.64057 YNL301C -0.271 1.23E-05 YER074W -0.051 0.44216 YPR102C -0.058 0.26052 YDR461W -0.526 5.52E-10 YDR184C 0.404 0.10407 YBL050W 0.106 0.23706 YCL067C 0.301 0.0027555 YDL014W -0.038 0.62955 YER133W -0.051 0.36616 YGL208W 0.139 0.097498 YGR136W -0.204 0.0020376 YBR170C 0.429 0.0016184 82

Gene ID Expression value p-value YHR141C -0.139 0.012998 YJL219W -0.162 0.097946 YNL214W 0.199 0.11918 YLR134W -0.351 1.21E-08 YCL040W -0.221 2.06E-04 YOL059W -0.591 1.53E-09 YLL021W -0.036 0.62229 YDL063C 0.971 0.0013668 YER065C 1.147 3.46E-08 YNR007C 0.161 0.10191 YLR044C -0.184 0.0064407 YIR009W -0.049 0.89526 YJL013C 0.084 0.52778 YDL215C 0 0.999999 YDR032C -0.211 7.14E-04 YJR066W 0.111 0.1951 YBR160W -0.405 0.026081 YDL081C -0.278 5.96E-06 YMR146C -0.151 0.072007 YBR135W 0.057 0.34065 YGL153W 0.627 0.0023167 YGL013C 0.173 0.0945 YMR005W 0.571 9.57E-05 YDL130W -0.24 2.14E-05 YDR299W 0.883 1.02E-04 YBR248C 0.898 3.30E-05 YGL008C -0.573 1.26E-06 YLR081W 0.892 7.34E-10 YER054C 0.247 0.0043603 YBR043C 0 0.999999 YMR291W -0.397 5.30E-09 YIL074C 0.393 0.022682 YNL036W 0.686 3.33E-07 YMR309C -0.123 0.1009 YLR319C 0.21 0.072655 YCR012W -0.746 4.23E-13 YOR178C -0.187 0.0036854 YPR145W -0.232 0.0011873 YEL039C -1.373 4.97E-07 YBR045C 0.94 0.016389 YBL026W -0.064 0.59933 YLR197W 0.49 3.38E-08 83

Gene ID Expression value p-value YOR361C -0.237 0.0031451 YAR007C -0.302 0.0060792 YNL098C 0.293 1.04E-04 YIL070C -0.339 9.00E-06 YLR117C 0.712 6.89E-06 YBL079W -0.42 2.95E-09 YJR109C -0.745 0.030981 YGL229C -0.208 0.28721 YGR058W -0.065 0.6708 YER052C 0.579 1.37E-05 YER111C 0.16 0.15558 YML054C -0.091 0.25421 YDR335W 0.272 0.2334 YPL222W 0.514 4.62E-05 YLR229C -0.154 0.030339 YIL061C 0.181 0.28119 YNL135C -0.169 0.0016167 YLR340W -0.361 2.06E-07 YIL015W -1.117 2.92E-11 YER040W 0.537 0.0018683 YDL078C -0.08 0.16505 YOL016C -0.138 0.027128 YFR034C 0.348 0.020802 YKL074C 0.608 3.45E-04 YDR323C 0.052 0.69287 YAL003W -0.146 0.013062 YOL127W 0.076 0.17224 YNL069C -0.124 0.026888 YPL211W 0.623 1.56E-04 YGR085C -0.084 0.1613 YIL113W -0.137 0.23739 YOR215C 0.335 1.27E-04 YJL030W 0.46 0.0045437 YJL157C 0.972 6.37E-07 YAL040C 0.303 0.0010074 YML032C 0.363 0.0030735 YOR326W 0.296 1.16E-04 YOL120C -0.62 3.90E-09 YNL145W -1.237 1.19E-10 YML123C 0.692 6.96E-07 YNL117W 0.941 1.26E-05 YGL044C 0.281 0.0057448 84

Gene ID Expression value p-value YCR084C -0.091 0.69411 YIL162W -1.131 1.74E-20 YOL123W -0.036 0.59496 YNL164C 1.345 5.79E-06 YML007W 0.331 0.0024709 YDL236W -0.258 8.10E-04 YKL101W 0.439 0.0030233 YOR290C -0.577 3.63E-13 YDL075W 0.056 0.38208 YLR191W 0.222 0.097987 YDR070C -0.089 0.1936 YGR048W 0.364 0.0043651 YLR214W 0.282 0.039051 YHR053C 0.795 1.52E-10 YOR036W 0.491 1.63E-06 YBR217W 0.378 0.012775 YML051W -1.167 8.20E-17 YPR048W 0.289 0.063048 YLR452C -0.269 0.014595 YOL149W 0.254 0.059331 YPL240C -0.661 6.77E-11 YOR315W -0.063 0.50938 YGR108W 0.101 0.1936 YGL122C 0.187 0.0059966 YIL143C 0.264 0.045357 YMR058W 0.64 1.60E-08 YGL035C -0.28 0.0070533 YBR050C 0.122 0.28411 YBR118W 0.044 0.54556 YPL089C 0.209 0.0026491 YHR179W -0.671 3.70E-11 YPL149W 0.488 1.56E-05 YLR377C 0.371 0.0037868 YNL167C -0.18 0.015501 YLR256W 0.104 0.2243 YBL021C -0.108 0.497 YMR311C 0.349 6.56E-06 YER079W -0.046 0.40867 YDR309C -0.798 1.26E-13 YLR258W -0.487 5.87E-12 YNL216W 0.234 0.54155 YJL190C -0.184 0.0020712 85

Gene ID Expression value p-value YDR395W -0.214 0.40913 YMR108W 0.095 0.14717 YPR041W -0.177 0.011738 YDR009W 0.162 0.16498 YJR048W -0.643 1.61E-08 YBR019C 2.856 3.94E-18 YAL030W 0.003 0.95396 YER081W 0.109 0.094304 YGR088W -0.394 3.07E-06 YPR035W -0.172 0.036009 YKL211C 0.358 1.53E-04 YER103W -0.826 8.37E-13 YNL236W -0.141 0.39009 YKL161C 0.202 0.18731 YLR362W 0.374 0.0010869 YDR167W 0.355 0.01484 YBR112C 0.077 0.17771 YGL097W 0.008 0.93826 YLR293C -0.128 0.012703 YGL166W 0.147 0.032147 YMR043W 0.457 2.41E-04 YGL237C 0.059 0.35299 YOR202W 0.239 0.0054895 YPR119W -0.342 1.64E-05 YPR113W -0.89 5.62E-18 YFR037C 0.35 0.0035541 YGL073W 0.543 6.23E-04 YGL115W -0.221 0.0027535 YER090W 0.231 0.0015768 YER124C -0.022 0.76846 YML114C 0.385 0.0058304 YLL019C 0.295 9.35E-05 YMR186W -0.608 1.68E-14 YJL159W 0.001 0.999999 YCR086W 0.381 0.17239 YJL036W 0.376 9.77E-04 YER145C 0.868 5.97E-07 YBR190W 0.07 0.66515 YDL030W 0.339 0.011822 YGL134W 0.839 3.76E-07 YML074C 0.389 3.32E-05 YML024W -0.864 1.31E-12 86

Gene ID Expression value p-value YJR022W 0.294 0.14344 YER102W -0.135 0.017595 YPL075W -0.53 5.27E-06 YDR354W -0.253 0.0012089 YJR060W 0.103 0.43529 YGR074W 0.029 0.80755 YER112W 0.151 0.13653 YNL154C -0.438 2.36E-07 YIL069C -0.018 0.74944 YML064C 0 0.999999 YLR432W -0.301 4.82E-05 YGL202W -0.536 3.89E-13 YOL086C -0.322 1.31E-05 YPL031C -0.139 0.019984 YKR026C 0.292 0.011229 YHR071W -0.499 6.81E-08 YKL028W 0.337 4.99E-05 YNR053C -0.012 0.90581 YLR153C -0.172 0.011567 YDL194W 0.449 0.011348 YGR009C 0.302 4.41E-04 YOR310C -0.157 0.041898 YDL088C 0.124 0.081403 ? null null YHR174W -0.217 0.0015357 YJL194W 0.525 0.050004 YMR300C 1.202 4.77E-11 YDR142C -0.069 0.401 YOL136C -0.472 0.0081753 YPR080W -0.278 6.78E-04 YNL091W 0.723 2.37E-04 YHR030C 0.21 0.0033506 YOR039W -0.006 0.92034 YBR018C 3.126 3.94E-17 YOR264W 0.307 0.011809 YLL028W -0.24 0.0047822 YFL026W -0.74 2.88E-14 YHR198C -0.379 5.43E-08 YLR345W 0.116 0.073789 YDR412W 0.991 2.47E-05 YKL109W -0.117 0.071395 87

B.2 Tadpole Network

Node ID Z-Score 0 -0.5244005 1 -0.5244005 2 -0.5244005 3 -0.5244005 4 -0.5244005 5 5.06895775 6 -0.5244005 7 -0.5244005 8 -0.5244005 9 0.39885507 10 3.5400838 11 3.4316144 12 1.16011988 88

B.3 Mouse Cell Cycle Pathway

Entrez ID Gene Name SLR 268697 Ccnb1 1.9 17220 Mcm7 0 18817 Plk1 -0.3 18538 Pcna 0 268930 Pkmyt1 2 15182 Hdac2 0.1 17128 Smad4 0 56150 Mad2l1 0.2 12581 Cdkn2d -0.1 12649 Chek1 0.3 26965 Cul1 -0.1 21809 Tgfb3 -1.9 22628 Ywhag 0.4 19090 Prkdc 0 668450 Gm9174 0 12443 Ccnd1 0 17127 Smad3 0 56371 Fzr1 -0.1 27214 Dbf4 0.1 56637 Gsk3b 0.2 12447 Ccne1 0.2 21781 Tfdp1 0 140557 Smc1b 0.2 19650 Rbl1 -0.2 12237 Bub3 0.5 50883 Chek2 0.1 17126 Smad2 0 17216 Mcm2 -0.2 22630 Ywhaq 0.6 12580 Cdkn2c 0 66671 Ccnh 0 12444 Ccnd2 0.2 12567 Cdk4 -0.1 66440 Cdc26 0.2 18392 Orc1l 0 66156 Anapc11 0.2 59008 Anapc5 0.1 17246 Mdm2 0.2 12566 Cdk2 0.1 54401 Ywhab 0.1 89

Entrez ID Gene Name SLR 12534 Cdc2a 0 19645 Rb1 0.3 12235 Bub1 -0.1 18393 Orc2l 0 56452 Orc6l -0.1 50793 Orc3l 1 56317 Anapc7 0 24061 Smc1a 0 12427 Ccna1 0.5 23882 Gadd45g -0.9 21402 Skp1a 0 12236 Bub1b 0.2 52563 Cdc23 0.3 17218 Mcm5 0 12578 Cdkn2a 1.8 12445 Ccnd3 0 27401 Skp2 0.1 13197 Gadd45a 0.9 100048076 LOC100048076 0 12428 Ccna2 0.1 433759 Hdac1 0 52206 Anapc4 0 229776 Cdc14a 0.5 100039786 Gm2423 0.6 12577 Cdkn1c 0.3 13555 E2f1 0.3 17215 Mcm3 -0.1 21808 Tgfb2 4.2 381759 Wee2 0 12531 Cdc25b 0 12571 Cdk6 0.1 68999 Anapc10 3.1 11920 Atm 0.4 328572 Ep300 -0.3 107995 Cdc20 0.1 242705 E2f2 0.4 12530 Cdc25a 0.1 12544 Cdc45l 0.3 17222 Anapc1 -0.1 12448 Ccne2 -0.1 217232 Cdc27 0.1 12545 Cdc7 0.4 90

Entrez ID Gene Name SLR 19651 Rbl2 0 12572 Cdk7 0.6 12576 Cdkn1b 0.1 640611 LOC640611 -0.1 22390 Wee1 0.2 69957 Cdc16 0 11350 Abl1 0.2 434175 Gm5593 -0.2 22629 Ywhah -0.1 17217 Mcm4 0 12532 Cdc25c 4 13557 E2f3 0.1 22627 Ywhae 0.1 12575 Cdkn1a 0.6 99152 Anapc2 0 22059 Trp53 2 100047564 LOC100047564 -0.1 209091 Ccnb3 3.4 17219 Mcm6 0.4 12914 Crebbp 0.2 30939 Pttg1 0.4 55948 Sfn -0.1 105988 Espl1 0 218294 Cdc14b 0.3 12442 Ccnb2 -0.4 17120 Mad1l1 0.6 56438 Rbx1 0.1 23834 Cdc6 0.2 71890 Mad2l2 -0.1 17873 Gadd45b 1.1 12579 Cdkn2b -0.1 22631 Ywhaz 0.5 26428 Orc4l 0.1 26429 Orc5l 0 21803 Tgfb1 0.8 91

Appendix C: Expression data and Annotations for KEGG Network

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 13684 Eif4e 1444010_at,1450909_at,1423220_at, 0.2 0 0.3 1.6 1.5 1450908_at 329502 Pla2g4e 1429862_at -0.2 -0.5 0.2 -0.5 -0.3 19045 Ppp1ca 1460165_at -0.1 -0.1 -0.2 0 0.2 12494 Cd38 1433741_at,1450136_at 0.1 0.3 0.3 1.1 -0.4 17347 Mknk2 1449029_at,1418300_a_at -0.1 -0.6 -0.7 -0.5 0.8 13840 Epha6 1421527_at 1.4 2.4 2.8 3 1.9 12385 Ctnna1 1436631_at,1437275_at,1448149_at, 0.7 0.1 0.4 0.6 0.1 1437807_x_at 16158 Il11ra2 1417505_s_at,1459868_x_at 0 -0.1 -0.2 -0.3 0.1 23805 Apc2 1450497_at,1422129_at,1435199_at, 0.6 0.9 0.4 0.5 0.5 1455231_s_at 12929 Crkl 1425604_at,1436950_at,1421953_at, 0 0.6 1 0.9 0.7 1421954_at 20698 Sphk1 1451596_a_at -0.1 -0.3 -0.1 -0.4 0.3 18096 Nkx6-1 1425828_at 0.2 0.3 1 0.2 0.8 12842 Col1a1 1423669_at,1455494_at 2.1 1.4 1.2 2.1 0.5 106628 Trip10 1418092_s_at 0 0.2 0.3 0.3 -0.4 12843 Col1a2 1450857_a_at,1423110_at,1446326_a 3.7 0.3 3.9 2.8 3.8 t 12995 Csnk2a1 1419037_at,1419038_a_at,1419036_a 0.3 0.5 0 -0.1 0.3 t,1453427_at,1419035_s_at,1419034_ at 27371 Sh2d2a 1449105_at 0.3 0.4 1.5 3.7 0 22151 Tubb2a 1427838_at,1427347_s_at -0.2 -0.4 -0.4 0.2 0.9 14859 Gsta3 1423436_at,1423437_at 0.2 -0.1 -0.3 -0.5 -0.1 14593 Ggps1 1429356_s_at,1419506_at,1419505_a 0 0.2 0.1 0.3 0.7 _at,1419805_s_at 13555 E2f1 1447840_x_at,1431875_a_at,1417878 0.3 1.8 0.2 0.3 0.8 _at 15013 H2-Q2 #N/A 0000 0 93960 Nkd1 1417278_a_at,1429506_at,1429507_a 3.3 1.5 0.1 3 1.7 t 18710 Pik3r3 1456482_at 0.4 0.8 1.5 0.6 0.1 26404 Map3k12 1417115_at,1438908_at,1456565_s_a 0.7 0.2 0.1 0.2 -0.1 t,1458198_at 23938 Map2k5 1430180_at,1455941_s_at,1453712_a 0.2 0.4 0.3 0.1 0.3 _at,1417854_at 26876 Adh4 1422070_at 2.4 0.9 0 0.4 1.9 22631 Ywhaz 1416103_at,1416102_at,1448219_a_a 0.5 1.1 0.7 0.4 0.1 t,1436971_x_at,1439005_x_at,144821 8_s_at,1436981_a_at 13821 Epb4.1l1 1421090_at,1434575_at,1460592_at 0.1 0 -0.1 -0.1 0.6 231602 P2rx2 1435212_at 0 0.2 0.6 0.4 0.3 21872 Tjp1 1417749_a_at -0.3 -0.1 0.6 1.2 1 387514 Tas2r143 #N/A 0000 0 69051 Pycr2 1448315_a_at 0 -0.5 -0.9 -1.5 -0.7 92

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 57377 Mogs 1422489_at -0.1 -0.5 -0.9 -1.7 -0.8 75590 Dusp9 1454737_at,1433844_a_at,1433845_x 1.6 1.7 1.3 0.6 1.7 _at 107477 Guca1b 1425138_at 0.2 0.5 -2.5 -0.6 -3.3 319625 Galm 1452583_s_at,1452582_at 0 0.1 0.2 -0.1 0.3 436522 Try10 1415954_at 0.7 0.2 -0.1 -0.3 2 214579 Aldh5a1 1453065_at -0.7 -0.2 -1.8 -2.1 -0.2 14309 Fshr 1450810_at -0.2 -0.2 -0.9 -0.6 -1.5 15974 Ifnab 1422403_at,1450593_at,1422404_x_a 2.2 1.7 4.5 3.5 1.3 t,1450613_x_at 22034 Traf6 1435350_at,1421377_at,1421376_at, 0.4 0.6 0.6 0.7 0.2 1446940_at,1443288_at 14347 Fut7 1420756_at 1 -0.4 0.4 0.1 0.6 16453 Jak3 1423021_s_at,1425750_a_at 0.2 0.7 0.3 0.4 0.8 224805 Aars2 1436017_at 0.3 0.3 0.1 0 -0.1 19294 Pvrl2 1424456_at,1417703_at 0.1 1 1.5 2 -0.1 94224 Srd5a2 1422960_at -0.5 0.4 -0.9 -2.1 -0.3 15874 Iapp 1423510_at,1437323_a_at,1456004_x 1.5 2 1.6 1.2 1.9 _at,1423509_a_at 26384 Gnpda1 1448163_at,1455065_x_at -0.1 -0.4 -0.8 -0.9 0.5 80796 Calm4 1450633_at 0.4 0 -0.7 0.1 0.3 208715 Hmgcs1 1441536_at,1433443_a_at,1433445_x 0.7 0 -0.5 -0.9 -1.3 _at,1433446_at,1433444_at 77777 Ulbp1 1431178_at -0.1 -0.2 -0.2 0.5 -0.4 22094 Tshb 1450371_at 0.1 0 0.5 -0.2 -0.7 19215 Ptgds 1423860_at,1423859_a_at 1.9 2.2 2 0.9 1.8 19051 Gsbs 1449240_at -2.4 0.7 -1.9 1 -1.2 14860 Gsta4 1416368_at -1.1 0.2 0 0 2.9 70059 Degs2 1424549_at 0.3 -0.8 0.8 -0.3 -0.2 11886 Asah1 1416735_at 0 -0.1 -0.1 -0.1 0 12315 Calm3 1423807_a_at,1438826_x_at,1422414 2.5 1.9 1.9 4.1 3.2 _a_at,1450864_at,1417366_s_at,1438 825_at,1426710_at 20652 Soat1 1448068_at,1417697_at,1417695_a_a 0 -0.1 -0.2 0 0.1 t,1417696_at 12834 Col6a2 1426947_x_at,1452250_a_at 1.6 1.6 1 0 2.7 170758 Rac3 1420554_a_at -3.6 -0.1 -2.4 -2.9 -1.5 218268 Eif4e1b #N/A 0000 0 13869 Erbb4 1427783_at -1.1 -0.5 0.1 1.4 1 242341 Atp6v0d2 1434798_at,1444176_at -0.1 -0.3 -0.3 -0.1 0.3 18037 Nfkbie 1431843_a_at,1458299_s_at 0.4 0.6 0.6 1.2 -0.3 16009 Igfbp3 1458268_s_at,1423062_at 3.6 0.9 0.1 2.8 0.3 21826 Thbs2 1447862_x_at,1450663_at,1422571_a 1.5 1.4 1.6 1.9 1.6 t 11723 #N/A 1416055_at 0.2 0.1 -0.5 -1 0 170736 Parvb 1422060_at,1438672_at 0.1 -0.2 0 -0.1 -0.4 54376 Cacng3 1450520_at -0.8 -0.8 -0.5 -1.3 -2.2 93

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 107652 Uap1 1416744_at,1416743_at,1416745_x_a 1.3 0.7 1 0.6 0.3 t,1456516_x_at,1437490_x_at 54391 Rfk 1416229_at,1415737_at,1416230_at 0.1 -0.1 0 -0.2 0 55984 Camkk1 1418954_at 0 0.3 -2.4 -0.3 -0.2 75788 Smurf1 1428395_at,1428396_at -0.1 -0.1 0.4 0.8 0.8 27401 Skp2 1425072_at,1449293_a_at,1418969_a 0.1 0 -0.7 -0.4 0.1 t,1437033_a_at,1436000_a_at,14602 47_a_at 12006 Axin2 1421341_at,1436845_at 1.5 1.6 2.1 1.9 1.8 69663 Ddx51 1428728_at 0 -0.3 -0.8 -1.2 -0.8 66171 Pgls 1417722_at -0.2 -0.2 -0.3 -0.7 -0.8 15484 Hsd11b2 1416761_at -0.6 -0.6 -0.6 -1.2 -1.4 11479 Acvr1b 1422098_at,1433725_at 1.1 0.9 1.7 0.2 -0.1 109648 Npy 1419127_at -0.2 0 -0.4 -0.2 0 13198 Ddit3 1417516_at,1443897_at -0.1 -0.6 0.6 2.1 3.4 17769 Mthfr 1434087_at,1450498_at,1422132_at 1.4 3.3 4.2 5.3 4.9 11785 Apbb1 1423892_at,1423893_x_at 0.2 -0.1 0.2 0.2 -0.1 12061 Bdkrb1 1450586_at -0.3 -1.2 -0.3 -0.3 -0.2 380794 Ighg 1426174_s_at,1424631_a_at,1451949 0.8 1.8 1.5 2.3 1.5 _at,1451632_a_at 14308 Fshb 1450996_at 0.5 0 -3.2 -3.8 -3.7 234515 Inpp4b 1441416_at,1457359_at 3.3 3.5 2.2 0.8 3.3 110279 Bcr 1452368_at,1455564_at,1427265_at 2.3 0.7 2.6 1.1 2.7 104318 Csnk1d 1456727_a_at,1449932_at,1437690_x 0 0.1 0.5 0.6 0.6 _at,1418889_a_at,1415825_s_at 20226 Sars 1452000_s_at,1426257_a_at 0.1 -0.1 -0.4 -0.7 0.1 18416 Otc 1436615_a_at,1420525_a_at,1425540 0.2 0.8 -1.2 0.7 1 _at 21802 Tgfa 1421943_at,1421942_s_at,1450421_a 0.1 1 0.6 0.2 2.5 t 20701 Serpina1b 1451513_x_at,1418282_x_at,1449321 0.2 0.5 0.6 0.5 0.5 _x_at 16164 Il13ra1 1451775_s_at,1427164_at,1427165_a 0.2 0.2 0.9 1.8 1.4 t,1454783_at,1425625_at 28200 Dhrs4 1419382_a_at,1451559_a_at 0.3 0.3 0.4 0.2 -0.1 100043202 Trav3d-3 #N/A 0000 0 71761 Amdhd1 1447380_at,1427370_at 0.1 0.2 0.3 1 2.6 58865 Tdh 1449064_at 0.8 1.1 -1 0.9 -0.6 13360 Dhcr7 1448619_at -0.2 -0.5 -1.5 -3.1 0.9 14064 F2rl2 1445680_x_at,1421407_at -0.1 0 -0.3 -0.8 -1.7 20425 Shmt1 1425178_s_at,1422198_a_at,1425177 0.5 0.5 0.7 0.5 -0.3 _at,1425179_at 19878 Rock2 1423592_at,1451041_at 0.3 -0.1 -0.6 -1.2 -0.5 13823 Epb4.1l3 1419062_at,1426010_a_at,1440595_a 1.4 2.8 2.5 1.9 3.2 t 13714 Elk4 1450549_s_at,1427162_a_at,1422233 0.3 0.1 0.1 0.3 -0.5 _at,1447571_at 94

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 11674 Aldoa 1416921_x_at,1434799_x_at,1439375 0.6 1.1 1.6 3.6 5.2 _x_at,1433604_x_at,1447734_x_at,14 53901_at 11628 Aicda 1420577_at 0.3 1.9 -0.8 1 0.8 394432 Ugt1a7c 1424783_a_at,1426260_a_at,1426261 -0.1 0.2 -0.1 -0.3 0.7 _s_at 18476 Pafah1b3 1416410_at 0.2 0.1 0.3 0.7 1.1 26565 Pla2g10 1451502_at -0.1 0.9 0.5 0.5 -0.3 234889 Gucy1a2 1459336_at -1.7 -0.5 -2.8 -3.7 -4 18762 Prkcz 1418085_at,1454902_at,1449692_at 0.5 0.6 0.9 1.1 0.4 20742 Spnb2 1444089_at,1419255_at,1441507_at, 0.3 0.1 2.2 0.5 0.5 1452143_at,1451830_a_at,1419256_a t 22341 Vegfc 1419417_at,1439766_x_at,1440739_a 3.5 3.3 2.9 2.2 0 t 69955 Fars2 1431354_a_at,1439406_x_at -0.1 0.1 -0.3 -0.6 0.4 18627 Per2 1457350_at,1417602_at,1417603_at 0.5 -0.7 -0.1 0.9 1.1 140570 Plxnb2 1416683_at -0.5 -0.4 -1 -0.1 0.5 16334 Ins2 1422446_x_at 0 0.1 2.9 0.1 0.3 22153 Tubb4 1423221_at -0.3 -0.2 -0.6 -0.5 0.4 15115 Hars 1417024_at,1438510_a_at 0 -0.1 -0.3 -0.8 -0.5 71562 Afmid 1431722_a_at,1447638_at,1428885_a 0.5 0.2 0.5 0.8 0.4 t,1452944_at 104111 Adcy3 1436928_s_at,1436929_x_at,1421960 0.3 0.3 0.1 1.3 0.5 _at,1421959_s_at 12036 Bcat2 1425764_a_at 0 -0.4 -0.7 -0.6 -0.8 13641 Efnb1 1451591_a_at,1418286_a_at,1418285 0.3 0.5 0.4 0.1 -0.3 _at 18778 Pla2g1b 1437015_x_at,1433949_x_at,1433948 1 3.2 1.4 1.3 3.9 _at,1416626_at 14179 Fgf8 1451882_a_at 0 0 -0.6 0.4 0.2 76429 Lhpp 1452889_at -1.4 -0.3 -0.9 -0.9 0.4 20963 Sykb 1425797_a_at,1457239_at,1418261_a 0 0 0 0.3 0.6 t,1418262_at 12824 Col2a1 1450567_a_at 0.2 0.2 -0.1 0.6 -0.2 11486 Ada 1417976_at 0.3 0.5 0.1 0.7 -1.1 26456 Sema4g 1449202_at -0.2 0.6 -0.6 -2.4 0.2 15562 Htr4 1443365_at,1427654_a_at 2 0.5 2.5 1.8 0.7 14450 Gart 1416283_at,1424435_a_at,1424436_a 0.6 0.3 0.2 -0.6 0.1 t,1441911_x_at 21915 Dtymk 1438096_a_at,1452681_at,1449116_a 0.1 -0.1 -0.8 -1.6 -1.5 _at 19370 Raet1c 1420603_s_at -0.5 -0.3 -1.2 -0.6 -1.3 109689 Arrb1 1460444_at 0 -0.1 -0.5 -1 0.1 13099 Cyp2c40 #N/A 0000 0 75454 Phpt1 1427903_at -0.2 -0.1 -0.2 -0.7 -1.5 16451 Jak1 1433805_at,1433803_at,1433804_at -0.1 0.1 0.3 0.6 1.3 95

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 67005 Polr3k 1422752_at,1439266_a_at,1422753_a 1.6 0.3 1 0.9 2.5 _at,1456731_x_at,1450737_at,144073 5_at 16337 Insr 1434446_at,1450225_at,1421380_at 1.1 1 1.6 1.8 0.7 13435 Dnmt3a 1423066_at,1423064_at,1423063_at, 0 0.1 0.6 1.3 2.5 1460324_at,1423065_at 66144 Atp6v1f 1423993_at 0.1 0 0.1 0.2 0.2 17855 Mvk 1430619_a_at,1418052_at -0.2 0.1 -0.3 -0.5 -0.5 26878 B3galt2 1437644_at,1437433_at,1423084_at 0.3 -0.6 -1.2 0.3 -0.9 71984 Sars2 1448522_at -0.5 -0.5 -0.6 -0.5 -1.7 114874 Ddhd1 1454070_a_at,1445438_at,1427289_a 0.8 0.9 1.7 2 0.4 t,1455321_at 337924 Cyp3a44 1426064_at 0.3 -3.6 -2.3 0.8 -3.3 58801 Pmaip1 1418203_at 0.3 0.6 0.6 0.7 0.5 16987 Lss 1426913_at,1420013_s_at,1420014_a 0.1 0.3 -0.7 0.5 -0.9 t 16886 Limk2 1439896_at,1452060_a_at,1418581_a 0.5 0.6 0 0.2 0.6 _at 192157 Socs7 1434834_at,1438492_at,1455402_at, 2.7 1.4 0.7 3.8 0.5 1420766_at 231727 B3gnt4 1451815_at 0.3 0.4 0.2 0.3 0.3 12988 Csk 1423518_at -0.2 0 0.3 0.3 0.4 108960 Irak2 1436507_at 0.3 1 1.3 1.7 1.8 13488 Drd1a 1456051_at,1455629_at 3 2.2 1.4 0.3 -0.3 224754 H2-M11 #N/A 0000 0 17187 Max 1423501_at 1.2 1.5 2.5 1.4 0.8 208211 Alg1 1451368_at -0.2 -0.1 -0.3 -1.2 -0.2 320011 Uggt1 1455839_at,1432318_at,1448009_at -0.1 -0.1 -0.4 -0.1 -1.1 12389 Cav1 1449145_a_at 0 0.5 0.8 1.1 0.4 14679 Gnai3 1428645_at,1437225_x_at 0 0.2 -0.1 -0.1 -0.2 11431 Acp1 1449604_at,1450721_at,1450720_at, 0.1 0.3 0.1 -0.4 -0.2 1422715_s_at,1422717_at,1422716_a _at 17221 Cd46 1421586_a_at -0.1 -0.4 -0.3 -0.1 -0.8 12483 Cd22 1419768_at,1419769_at -0.2 -0.3 -0.8 -1 -0.4 13074 Cyp17a1 1417017_at 0.1 -0.1 0.3 0.3 1.1 69083 Sult1c2 1449409_at -0.1 0.1 1.2 -0.9 -0.8 14366 Fzd4 1419301_at,1449416_at -0.2 0.2 -2.4 0.9 0.3 22408 Wnt1 1425377_at -0.2 1.8 1.5 0.4 -1.3 13090 Cyp2b19 1419731_at 2.3 -1.2 -0.7 1.6 0.4 93897 Fzd10 1440182_at,1455689_at 0.2 0.9 1.6 2.7 0.7 56248 Ak3 1423718_at,1423717_at,1432436_a_a -0.2 -0.2 -0.2 -0.5 0 t 56405 Dusp14 1431422_a_at 1.6 2.3 1.7 2.2 2.1 18797 Plcb3 1448661_at 0.2 0.5 0.8 1 0.1 233733 Galntl4 1454780_at -0.7 -0.5 -1.1 -0.3 0.1 96

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 74450 Pank2 1458358_at,1431948_a_at,1452733_a 0 0.1 0.4 0.4 0.6 t 14296 Frat1 1449814_at 0.2 0.3 0.1 0.2 0.2 22236 Ugt1a2 1424783_a_at,1426260_a_at,1426261 -0.1 0.2 -0.1 -0.3 0.7 _s_at 106042 Prickle1 1444759_at,1452249_at -0.9 0.1 -2.6 0 -2.2 71887 Ppm1j 1453127_at -0.4 0.1 -0.3 -0.5 -1.4 387616 Tas2r140 #N/A 0000 0 170442 Bbox1 1459030_at,1419618_at 0.3 0.5 1.8 0.6 0.1 13838 Epha4 1456863_at,1421929_at,1439757_s_a 1 1.8 1.2 1.4 -0.2 t,1429021_at,1421928_at 13078 Cyp1b1 1416612_at,1416613_at,1432081_at 1.4 3.5 4.1 4.7 4.1 70266 Ccbl1 1452678_a_at,1446302_at,1438348_x 1.7 1.8 0.9 0.6 2.7 _at,1428151_x_at 54195 Gucy1b3 1420872_at,1420871_at 1.2 0.6 2.2 0.1 1.5 54004 Diap2 1442003_at,1427564_at -0.2 0 0 0.2 -0.1 56863 Cldn9 1450524_at,1439427_at 2.6 0.1 0.6 0.8 0.4 207728 Pde2a 1447708_x_at,1452202_at,1447707_s 0.2 -0.1 0.3 0.9 1.1 _at 16867 Lhcgr 1450192_at 0.2 0.9 2.8 0.4 -0.1 16456 F11r 1436374_x_at,1424595_at 0 0 0.5 0.5 0.3 20379 Sfrp4 1451031_at -0.1 0.1 0 -0.2 0 170770 Bbc3 1423315_at 0.3 0.6 0.4 -0.4 -0.7 60533 Cd274 1419714_at 0.6 1.8 2.3 2.7 2.4 16396 Itch 1459332_at,1415769_at,1440582_at, 0.3 0.2 0.5 0.1 0.2 1431316_at 433323 Sgpp2 1457867_at 0.1 0.2 -0.2 0.6 -0.3 14600 Ghr 1451871_a_at,1417962_s_at,1451501 1.6 1 1.6 2.7 3.1 _a_at 13119 Cyp4a14 1423257_at -2.1 -0.3 0.4 -1.3 -0.1 242517 Gm12597 1422404_x_at,1450593_at,1422403_a 0.5 1.2 4.5 3.5 1.3 t 71740 Pvrl4 1428701_at,1451690_a_at 0.8 1.3 1.8 2 1.4 19108 Prkx 1451299_at,1424287_at,1424286_at -0.1 0.3 0.7 0.7 0.3 23827 Bpnt1 1449211_at,1418764_a_at -0.1 -0.1 -0.2 -0.4 -1 14775 Gpx1 1460671_at 0.1 -0.1 0 0.1 0.2 15357 Hmgcr 1451766_at,1427229_at 0.1 -0.1 -0.2 -0.9 -1.7 71586 Ifih1 1426276_at 1.2 4.3 5 5.2 3.9 14420 Galc 1452907_at,1449900_at,1420547_at 1.5 0.1 0.7 -0.6 0 56690 Mlycd 1449964_a_at -0.1 -0.2 -0.8 -0.6 -0.5 20469 Sipa1 1416206_at 0 -0.7 -0.9 -1 0.1 387340 Tas2r104 #N/A 0000 0 109857 Cbr3 1427912_at -0.2 0.1 -0.1 -0.8 -0.2 72535 Aldh1b1 1451260_at -0.3 0.5 1.9 2 1.4 19139 Prps1 1416052_at,1448192_s_at 0.1 0 -0.7 -1.1 -1 72935 Ddx41 1423814_at -0.1 -0.1 -0.1 0 0 97

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 71751 Map3k13 #N/A 0000 0 71685 Galnt14 1453630_at -0.5 0.7 1.4 0.4 0.1 269823 Pon3 1419298_at -0.1 -0.1 -0.1 0 0.1 11432 Acp2 1424655_at,1424654_at,1436788_at 0.1 0.1 0.3 1 1 18715 Pim2 1417216_at -0.1 0.3 0 -0.1 0.1 20190 Ryr1 1427306_at,1457347_at 0 -0.1 0.4 0.3 0.5 22171 Tyms 1427810_at,1424991_s_at,1427811_a 3.8 2.7 0.9 3.4 2.6 t,1442192_at,1438690_at 56637 Gsk3b 1439931_at,1434439_at,1437001_at, 0.2 0.4 0.3 0.3 0.3 1454958_at,1439949_at,1451020_at

15039 H2-T22 1449875_s_at,1439121_at 0.1 2.5 3.5 4.4 3.8 226105 Cyp2c70 1424273_at -0.3 0.1 0.2 0.4 -0.5 19047 Ppp1cc 1452046_a_at,1450149_a_at 0.1 -0.2 -0.4 -0.8 -0.3 12739 Cldn3 1434651_a_at,1451701_x_at,1460569 2 2 2.4 2.7 1.2 _x_at,1426332_a_at,1453258_at 14923 Guk1 1416395_at -0.2 0 0.4 0.4 0 225994 BC016495 1425646_at,1448048_at,1447503_at 1.5 0.3 1.4 0.3 1.3 27267 Cars 1452394_at,1427330_at 0.3 0.2 0.5 0.6 1.1 20130 Rras 1418448_at -0.1 -0.2 -0.3 0.1 0.7 29858 Pmm1 1424167_a_at,1430780_a_at -0.1 -0.1 -0.5 -0.9 0 16639 Klra8 1425436_x_at,1425417_x_at 0.7 0.6 0.5 0.8 0.8 14365 Fzd3 1420087_at,1450135_at,1421157_at, 1.3 1 0.5 1.2 0.1 1449730_s_at 11909 Atf2 1452116_s_at,1426583_at,1426582_a 0.4 -0.1 -0.1 0.2 -0.6 t,1427559_a_at,1437777_at 11459 Acta1 1427735_a_at 0.4 0.2 -0.1 0.6 -1.8 70503 Ddo 1454025_at,1453499_at,1451650_at, -0.8 0.1 0.4 -0.1 -0.5 1439096_at 11554 Adrb1 1423420_at 0.1 -0.9 -3.7 -0.6 -0.2 14011 Etv6 1434880_at,1423401_at 0.1 0.3 0.6 1.4 0.5 13617 Ednra 1433525_at,1440093_at,1460513_a_a 1.9 2.6 2.3 0.3 0.4 t,1451691_at 632223 #N/A #N/A 0000 0 26396 Map2k2 1415974_at,1460636_at 0 0 -0.2 -0.2 0.3 320404 Itpkb 1441058_at,1435272_at 0.1 0.3 1.5 1.9 1.5 21338 Tacr3 1450278_at,1437029_at,1440803_x_a 0.2 1.4 0.6 1.6 -0.2 t 11669 Aldh2 1448143_at,1437410_at,1434988_x_a -0.3 -0.1 0.2 0.4 -0.1 t,1457155_at,1434987_at 11515 Adcy9 1418586_at,1419811_at,1449620_s_a 0 -0.3 -0.4 -0.2 1.5 t,1434454_at 14813 Grin2c 1449245_at 0.1 0.2 0.2 0.3 0.4 15967 Ifna4 1422404_x_at,1422408_at,1422403_a 3.9 3 7.8 5.9 1.3 t,1450593_at 21894 Tln1 1457782_at,1448402_at,1436042_at 0 -0.1 0.1 0.3 0.3 56360 Acot9 1418073_at,1449968_s_at 0 0.2 0.4 0.3 -0.3 98

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 26416 Mapk14 1416704_at,1451927_a_at,1426104_a 0.4 0.3 0 -0.6 -0.6 t,1416703_at,1459617_at,1442364_at

51792 Ppp2r1a 1415819_a_at,1455929_x_at,1438383 0 0.1 0.3 0.4 0.4 _x_at,1438991_x_at,1438174_x_at

102448 Xylb 1426706_s_at -0.3 -1.5 -1 -4 -4 109674 Ampd2 1426757_at,1438941_x_at 0 -0.3 -0.9 -0.8 -0.6 66447 Mgst3 1448300_at,1450563_at 1.2 0 -0.1 -0.5 -0.4 14268 Fn1 1437218_at,1426642_at 1.1 -0.1 -0.5 -1 -3.2 16889 Lipa 1423141_at,1423140_at,1450872_s_a -0.1 0.2 0.4 0.4 0.9 t 237313 Il20ra 1446498_at -0.1 -0.8 -1.2 -1.5 -0.9 14178 Fgf7 1438405_at,1422243_at 1.7 1.6 0.3 -0.1 -1 15894 Icam1 1424067_at 0.5 1 1 1.1 -0.6 19252 Dusp1 1448830_at 0.5 -0.4 0.4 1.2 1 11920 Atm 1421205_at,1428830_at 0.4 0.7 1.1 1 -0.2 11854 Rhod 1419061_at -0.6 0.2 -0.5 -3.3 0 224756 H2-M1 #N/A 0000 0 19208 Ptcra 1421760_at -2.4 -0.9 0.3 -1.6 -1.6 12371 Casp9 1437537_at,1457816_at,1426125_a_a 0.3 0.4 0 0.3 0.3 t 381813 Prmt8 1435204_at 0.3 0.7 1.4 0 0.5 242202 Pde5a #N/A 0000 0 16782 Lamc2 1421279_at,1452505_at 0.1 0.5 0.4 0.7 0.6 110135 Fgb 1428079_at 0.5 0.5 1 0.9 -0.1 73914 Irak3 1430704_at,1435040_at 0 0.2 -0.1 0 0.6 22628 Ywhag 1420816_at,1450012_x_at,1420817_a 0.4 0.4 0.5 0 0.1 t,1459693_x_at 14725 Lrp2 1427133_s_at,1445901_at,1452320_a 0.4 0.8 0.6 0.7 -0.1 t 17973 Nck1 1447271_at,1424543_at,1421487_a_a 0.6 0.5 0.7 0.9 0.6 t 208846 Daam1 1458662_at,1455244_at,1431035_at 0.5 1.4 2 1.7 0.5 15964 Ifna11 1422332_at 0.7 1 2.4 1.3 3 270190 Ephb1 1455188_at 1 2.2 1.2 1.7 1.7 22238 Ugt2b5 1419622_at 0.6 -0.7 3 -0.3 2.4 12475 Cd14 1417268_at 0.1 0.1 0 0.4 0.7 21960 Tnr #N/A 0000 0 14388 Gab1 1417694_at,1448814_at,1417693_a_a 0.6 0.6 -0.7 0.4 0 t 12295 Cacnb1 1426108_s_at,1451834_at,1425777_a 0.6 0.1 0.2 0.5 -0.1 t 15007 H2-Q10 1425137_a_at 0.2 3 2.6 3.4 2.6 18129 Notch2 1455556_at,1451889_at 0.2 2.5 1.9 3.7 4.3 18595 Pdgfra 1421916_at,1421917_at,1438946_at 1.7 2.5 0.9 3.2 0.7 14159 Fes 1452410_a_at,1427368_x_at -0.1 -0.3 -0.1 -0.3 -0.1 99

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 18854 Pml 1448757_at,1456103_at,1459137_at 0.1 1.9 2.8 2.6 3.2 74192 Arpc5l 1452044_at,1436421_s_at,1441190_a 0.3 0.3 0.3 0.7 0.2 t,1444011_at 94181 Nans 1417774_at,1417773_at 0.3 0.1 -0.2 -0.9 -0.7 74134 Cyp2s1 1428283_at -0.8 -0.1 -0.6 -0.4 -0.3 26970 Pla2g2e 1434852_at,1421325_at,1420674_at 0.6 2.2 1.6 0.8 0.1 13636 Efna1 1416895_at,1448510_at 0.1 0.5 0.5 0.2 0.7 54140 Avpr1a 1418603_at,1418604_at 0.3 1 0.2 -0.2 -0.3 12790 Cnga3 #N/A 0000 0 13110 Cyp2j6 1440691_at,1417952_at -0.2 0.9 0 0.5 0.6 75475 Oplah 1424359_at -0.9 -0.9 -2 -2.7 1.6 20846 Stat1 1450033_a_at,1440481_at,1420915_a 0.6 4.1 3.9 3.9 4 t,1450034_at 14661 Glud1 1416209_at,1448253_at -0.1 -0.1 -0.1 -0.4 -0.1 109711 Actn1 1428585_at,1452415_at,1427385_s_a 0.2 0.1 0.3 0.7 -0.1 t 20844 Stam 1416862_at,1459427_at,1416861_at, 0.5 0.8 1.1 0.1 1.7 1457828_at 26971 Pla2g2f 1421325_at,1434852_at 0.6 2.2 1.6 0.8 0.1 238505 Mtr 1439811_at,1458532_at 0.1 0.2 0.2 -0.3 -0.8 12669 Chrm1 1450833_at,1439611_at 1 1.6 0.3 0.6 0.1 56632 Sphk2 1417431_a_at,1426230_at 0.3 0.1 0.5 0.6 1.2 13063 Cycs 1445484_at,1422483_a_at,1456071_a 0 0 0.3 0.4 0.1 _at,1422484_at 18802 Plcd4 1432928_at,1437030_at,1432927_at 3.4 3 3.5 1.3 3.3 66902 Mtap 1424426_at,1451346_at,1451345_at, 0 -0.3 -0.7 -1.6 -1.8 1424425_a_at 11947 Atp5b 1416829_at 0 0 -0.1 -0.1 -0.1 14862 Gstm1 1425626_at,1425627_x_at,1448330_a 0.2 0.3 0.2 0.4 1.3 t,1416416_x_at 99663 Clca6 1439727_at,1447394_at 0.6 0.7 0.3 0.6 4.7 20440 St6gal1 1420928_at,1420927_at,1443581_at 0.1 0.2 -0.3 -0.3 0 11564 Adsl 1418372_at -0.2 -0.3 -1 -2 -1.2 64176 Sv2b 1435687_at,1434800_at 0.7 0.3 -0.4 0.9 0.5 13072 Cyp11b2 1450574_at 1.6 3.5 -0.1 1.2 2.1 14082 Fadd 1416888_at,1446499_at 0.1 0.1 0.4 0.2 0.1 20662 Sos1 1421885_at,1434389_at,1421884_at, 0.2 0.4 1 0.2 0.6 1431311_at,1421886_at 21827 Thbs3 1416623_at 2.4 0.8 1.9 0 0.4 228033 Atp5g3 1454661_at 0.2 0.1 0 -0.3 -0.3 110821 Pcca 1447577_x_at,1451405_at 0.3 0.5 0.4 0.6 0.2 15481 Hspa8 1431182_at,1420622_a_at,1420623_x 0.6 -0.1 -0.4 0 -0.1 _at,1455789_x_at 12540 Cdc42 1415724_a_at,1435807_at,1460708_s 0.1 0.1 0.1 0.3 0.1 _at,1449574_a_at 18781 Pla2g2c 1420584_at 0.3 0.2 -0.2 0.2 -1.3 13142 Dao 1420709_s_at 0.8 -1.6 1.6 1.1 0.7 100

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 246221 Mpst 1418356_at 1.3 1.5 1.3 0.9 0.8 60595 Actn4 1423449_a_at 0 -0.1 -0.4 -0.7 0 224753 H2-M10.4 #N/A 0000 0 18125 Nos1 1438483_at,1422949_at,1458626_at, 3.8 0.5 3.7 1.6 2.9 1429887_at 11925 Neurog3 1432034_at,1422312_a_at 0.5 1.8 -0.1 0.5 1.1 107869 Cth 1426243_at -0.3 -0.6 0.6 -0.3 -3.9 13874 Ereg 1419431_at 2.9 4.4 2.2 1.8 -0.5 102247 Agpat6 1450776_at,1422841_at 0.2 0.8 -0.2 0.5 0.3 71336 Rbks 1424841_s_at,1424840_at 0.1 -0.1 -0.2 0.2 0.6 110854 Ppp2r4 1439393_x_at,1448138_at,1439383_x 1.1 0.1 -0.3 0.2 0.2 _at 18947 Pnliprp2 1437438_x_at,1448186_at -0.3 0.1 0.9 0.2 2.3 212111 Inpp5a 1433605_at 0 -0.2 -0.7 -0.6 -0.2 73934 4930412D2 1432477_at 0.7 1.2 0.3 0 0 3Rik 29859 Sult4a1 1433714_at,1421606_a_at 3.4 1.2 1 0.4 0 14873 Gsto1 1416531_at,1456036_x_at 0 0 0.1 0.1 0.3 20916 Sucla2 1452206_at,1430402_at,1447056_at 0 -0.1 -0.2 -0.4 0 14784 Grb2 1449111_a_at,1418508_a_at -0.1 0 0.3 1 1 19247 Ptpn11 1427699_a_at,1421196_at,1451225_a 1.1 1.6 2.1 1.6 0.5 t 15370 Nr4a1 1416505_at 0.7 0.2 0.6 1.3 0.6 117147 Acsm1 1418668_at -1 1.7 1.7 0 -1.2 18590 Pdgfa 1418711_at,1449187_at 0.2 -0.6 -0.2 -0.4 -0.7 12167 Bmpr1b 1443720_s_at,1437312_at,1422872_a 2.9 1.5 2.2 3.1 0.7 t 108071 Grm5 1455272_at,1456119_at 0.7 3.3 0.6 3.1 4.1 20104 Rps6 1416141_a_at,1416142_at,1453466_a 0.2 0.8 0.1 -0.2 -0.4 t,1455693_x_at,1435816_at,1435962_ at,1437246_x_at,1435817_x_at,14343 77_x_at,1454620_x_at,1455981_at

58988 Rps6kb2 1422268_a_at 0 -0.2 -0.3 -0.2 0.1 14676 Gna15 1421302_a_at -0.1 0.2 0.9 0.6 0.2 382562 Pfn4 1428665_at 0.3 1.3 0.1 0.4 1.8 67800 Dgat2 1422678_at,1422677_at 0.3 0.7 0.5 0.7 0.5 94192 C1galt1 1428490_at,1422772_at,1450745_at -0.1 -0.4 -0.7 -0.8 -0.3 67375 Qprt 1418836_at,1418837_at 0.4 0 0.1 -0.3 0.2 72017 Cyb5r1 1424048_a_at 0.1 -0.1 -0.4 -1.5 0.1 12395 Runx1t1 1427640_a_at,1444615_x_at,1440310 1.2 4.1 1.1 0.8 4.6 _at,1443788_at,1437784_at,1448785 _at 13806 Eno1 1431111_at,1432829_at,1427404_x_a 3.1 2.8 3.7 1.6 2.2 t,1419023_x_at,1419022_a_at 12675 Chuk 1428210_s_at,1451383_a_at,1417091 0.2 -0.1 -0.1 -0.3 0 _at 15493 Hsd3b2 1460232_s_at,1425127_at 1.8 0.4 1.6 0.5 2.2 101

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 15566 Htr7 1422235_at,1435332_at 1 1.6 1.5 1.9 1.8 15450 Lipc 1419560_at -2.4 0.7 -1.8 -2.3 0.9 15485 Hsd17b1 1449392_at -0.6 0.4 -0.1 -1.9 0.1 319520 Dusp4 1428834_at 0.6 0 -0.4 -0.9 -0.5 18577 Pde4a 1421535_a_at 0.1 0 -0.1 -0.2 -0.2 67071 Rps6ka6 1429759_at,1429760_at 2.5 1.2 1.6 1.7 0.7 319945 Flad1 1424422_s_at,1424423_at,1424421_a 0.2 0 0 0 0.8 t 12442 Ccnb2 1450920_at -0.4 -0.1 0.2 -1.1 -2.7 74185 Gbe1 1420654_a_at -0.2 0.2 0.4 0.4 0.4 16640 Klra9 1425436_x_at 0.2 0.6 0.5 0.8 0.8 15452 Hprt 1448736_a_at -0.1 -0.1 -0.4 -0.9 -1.1 12402 Cbl 1434829_at,1450457_at,1455886_at -0.1 -0.1 -0.2 -0.2 -0.4 58187 Cldn10a 1426147_s_at -0.1 0.2 1.2 1.3 0.7 56077 Dgke 1423000_a_at,1438078_at,1436547_a -0.2 0 -0.1 -0.1 0.1 t 11464 Actc1 1415927_at -0.1 0.1 -0.2 -0.3 -0.4 24117 Wif1 1425425_a_at 0.5 3 2.2 4 -0.7 12896 Cpt2 1447820_x_at,1416772_at 0.8 0.7 0.7 0 0.3 11984 Atp6v0c 1416392_a_at,1438925_x_at,1435732 0.1 0 0.1 0.1 0.4 _x_at 243816 Gp6 1446554_at -0.2 -0.2 -1 0.5 0.7 54342 Gnpnat1 1423157_at,1423158_at,1423156_at, 0.2 0.6 -0.5 0.6 0.8 1457807_at 19056 Ppp3cb 1446149_at,1433835_at,1428473_at, 0.6 0.2 0.1 0.6 0 1427468_at,1428474_at 19369 Raet1b 1420603_s_at -0.5 -0.3 -1.2 -0.6 -1.3 75572 Acyp2 1427943_at 0.1 0 0.2 1 1.1 70408 Polr3f 1431999_at,1430328_at,1451773_s_a 3.2 3 1.3 0.1 2.5 t,1429686_at,1439075_at 11684 Alox12 1422700_at,1422699_at 1.1 1.3 2.1 2.7 -0.2 240672 Dusp5 #N/A 0000 0 18746 Pkm2 1417308_at 0000 0.4 16400 Itga3 1460305_at,1421997_s_at,1455158_a 1.6 0.3 2.1 0.2 0.1 t 12774 Ccr5 1422259_a_at,1424727_at,1422260_x 0.1 -0.6 -0.2 -0.1 0.2 _at 15242 Hhex 1423319_at -0.3 0.7 1 0.4 0.4 242687 Wasf2 1454673_at,1438683_at 0 0.1 0.2 0.2 0.4 11796 Birc3 1425223_at,1421392_a_at 0.8 0.8 1.3 1.4 0.7 224020 Pi4ka 1435003_at,1457379_at -0.2 -0.1 0 0 -0.5 22239 Ugt8a 1419063_at,1419064_a_at 4.6 0.7 4.2 0.1 2.3 77987 Ascc3 1457900_at,1457069_at 0.3 0.4 0.9 1.4 0.5 13537 Dusp2 1450698_at 1.2 0.5 0.1 0.1 -2.6 66681 Pgm1 1453283_at,1451149_at -0.1 -0.1 0 1 1.4 26361 Avpr1b 1422204_at 3.2 0.5 0.4 3.6 3.7 102

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 19204 Ptafr 1427872_at,1427871_at 0.3 0.9 1.6 1.6 2.2 18607 Pdpk1 1416501_at,1415729_at 0.2 -0.1 0 0.2 0.2 207521 Dtx4 1436545_at,1455711_at 0.1 0.4 -0.2 0 0.7 16193 Il6 1450297_at 5.5 5.9 6.7 7.1 3 108099 Prkag2 1431263_at,1451140_s_at,1423831_a 0.1 0.3 0.5 -1.9 -0.5 t,1423832_at 14171 Fgf17 1421523_at,1456239_at 1.2 2.9 1.6 0.5 0.9 11652 Akt2 1424480_s_at,1455703_at,1421324_a 0.1 0.4 0.8 0.9 0.7 _at 12290 Cacna1e 1421692_at 0.5 0.2 0 -0.5 0.9 268902 Robo2 1458229_at -0.5 -2.4 -0.7 -2.6 0.9 27388 Ptdss2 1429492_x_at,1439984_at,1460010_a 0.5 0.5 -0.1 0.4 2.1 _at,1453164_a_at,1450354_a_at,143 4587_x_at,1434586_a_at,1426728_x_ at,1458387_at 142980 Tlr3 1422781_at,1422782_s_at -0.1 1.8 4.1 4.5 3.6 13121 Cyp51 1422534_at,1422533_at,1450646_at 0.1 0 -1.1 -0.1 -0.2 13909 Gm4738 1451600_s_at 0.2 0.5 -0.4 -0.2 -2.4 14125 Fcer1a 1421775_at 0.8 1 3.9 3.5 0.8 14645 Glul 1426235_a_at,1426236_a_at 0.1 -0.2 -0.5 -0.6 0.7 66401 Nudt2 1418737_at 0 -0.2 -0.5 -0.7 -0.4 14175 Fgf4 1420085_at,1450282_at,1420086_x_a 0.3 2.1 3.3 1.9 1.6 t,1449729_at 71670 Acy3 1448539_a_at 0 0.7 0.3 -0.7 2 12946 Cr1l 1438920_x_at,1422563_at,1430131_a 0.3 0 0.2 0.1 0 t 208665 Akr1d1 1425771_at,1455100_at 1.1 0.2 -0.4 0.1 -2.8 57170 Dolpp1 1428072_a_at 0.1 -0.3 -0.5 -0.9 -0.5 13200 Ddost 1416493_at -0.2 -0.2 -0.2 -0.2 -0.6 14151 Fech 1418698_a_at,1418699_s_at,1449181 0.3 0 -0.1 0.1 0.4 _at,1427696_at 78894 Aacs 1451116_at,1423797_at,1456081_a_a -0.1 -0.3 -1 -1.1 -1.1 t 12766 Cxcr3 1449925_at -0.5 -0.1 -0.1 0 -0.8 26406 Map3k3 1426686_s_at,1436522_at,1426687_a 0.9 0.8 0.3 0.2 0.6 t 12722 Clca1 1460259_s_at,1417852_x_at,1417853 3.5 4.6 1.6 2.1 0.7 _at 16627 Klra1 1428056_at,1452645_x_at 0.1 0.4 -1.3 -1.9 -2.8 56012 Pgam2 1418373_at 0.2 0 -0.3 0.2 -0.4 11863 Arnt 1437042_at,1449696_at,1421721_a_a 0.5 0 -0.2 0.1 0.2 t,1425064_at,1419996_s_at 17906 Myl2 1448394_at 1.5 0.7 -2 0 -0.2 81877 Tnxb 1450798_at 0.5 1.7 0.4 0.7 2.1 19211 Pten 1455728_at,1457493_at,1422553_at, 0.1 0.1 -0.3 -0.2 0.1 1450655_at,1454722_at 387339 Tas2r102 #N/A 0000 0 112407 Egln3 1425918_at,1418649_at,1418648_at 0.1 -0.1 0.4 0.3 0.4 103

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 68655 Fndc1 1453321_at,1430119_at 0.3 0.2 2.5 0.4 0.3 14816 Grm1 1425700_at 1.7 1.1 -0.8 1.6 0.9 14186 Fgfr4 1418596_at,1427845_at,1427776_a_a 1.1 0.9 4 1 0.4 t,1427777_x_at,1427846_x_at 74442 Sgms2 1428663_at,1429029_at 0.1 0.5 0.1 0.7 0.3 20613 Snai1 1448742_at -0.4 0.8 0.2 0.3 0.5 17960 Nat1 1421758_at 0.6 0.6 0.6 0.8 0 13434 Trdmt1 1419750_at,1419749_at 1.5 3 1.7 0.9 -0.2 16169 Il15ra 1448681_at,1422397_a_at -0.1 2 3.6 4.1 2.7 14376 Ganab 1437812_x_at,1415787_at -0.1 -0.1 -0.1 0.1 -0.6 14811 Grin2a 1421616_at 0.6 3.1 3.2 0.8 2.6 12326 Camk4 1452572_at,1426167_a_at,1439843_a 1.4 0.4 1 0.8 1.6 t,1441974_at,1421941_at 14071 F9 1427393_at -0.4 0 -0.3 -0.2 0.1 18783 Pla2g4a 1448558_a_at 0 0.2 0.9 1.5 0.3 57253 Tas2r108 1450605_at 1.2 2 0.2 2.4 1.4 19164 Psen1 1450399_at,1425549_at,1420261_at, 1.2 0.2 0.3 0.5 0.8 1421853_at 434782 Gm5637 1416227_at -0.1 -0.2 -0.3 -0.5 -0.8 211347 Pank3 1426259_at,1433613_at 0 0 -0.3 -0.7 -0.8 18679 Phka1 1422743_at,1422744_at,1435567_at 1.1 0.7 0.2 1.5 2.9 18782 Pla2g2d 1454157_a_at,1418987_at 0.9 1 2.6 2 1.5 57255 Cldn13 1422920_at -1.7 0.2 -0.3 -0.3 -0.3 109801 Glo1 1424109_a_at,1451240_a_at,1424108 0.1 -0.1 -0.5 -1.2 -1.2 _at,1436070_at 12702 Socs3 1416576_at,1455899_x_at,1456212_x 1.9 1.7 2.1 1.9 0.3 _at 73916 Ift57 1446696_at,1418929_at 0.1 0.3 0.3 -0.1 -0.2 13244 Degs1 1423346_at,1423345_at 0 -0.1 -0.1 -0.3 -0.3 192897 Itgb4 1427387_a_at -0.4 2.2 0.6 0.2 -0.4 53970 Rfx5 1423103_at 0.3 0.6 1.3 1.7 -0.1 208650 Cblb 1437304_at,1455082_at,1458469_at 0.9 0.4 0.8 1.3 0.9 227613 Tubb2c 1423642_at,1456031_at,1439416_x_a 2.4 3.3 0 3.6 3.6 t,1456470_x_at,1456078_x_at,143862 2_x_at 74147 Ehhadh 1448382_at -0.2 -0.7 -1.1 -0.7 -0.1 241656 Pak7 1446159_at,1455847_at,1440981_at 1.8 3 0.5 3.3 3.9 19877 Rock1 1460729_at,1450994_at,1423444_at, 0.1 0.3 0.6 0.3 -0.2 1441162_at,1423445_at 20528 Slc2a4 1415959_at,1415958_at 0.1 -0.7 -0.8 0.1 -0.7 20970 Sdc3 1420853_at,1436482_a_at,1450027_a -0.2 0.1 0.9 1.4 2 t 13388 Dll1 1419204_at 0.2 0.7 0.7 0.5 -0.7 104

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 18563 Pcx AFFX- 0.3 0.4 0.8 0.2 0.2 PyruCarbMur/L09192_5_at,AFFX- PyruCarbMur/L09192_MA_at,AFFX- PyruCarbMur/L09192_MB_at,AFFX- PyruCarbMur/L09192_3_at,1416383_ a_at 98256 Kmo 1418998_at 0.2 -0.1 0.3 -0.2 -1.9 14939 Gzmb 1419060_at 0.1 0.6 1.9 0.7 0 18578 Pde4b 1446577_at,1444731_at,1422474_at, 2.6 1.2 3.1 2.2 2.2 1442700_at,1447718_at,1422473_at

20617 Snca 1436853_a_at,1431022_at,1418493_a 3.4 3.5 3.3 2.4 3.6 _at 13639 Efna4 1421784_a_at -0.9 0 -0.6 -1.1 -2.8 17879 Myh1 1427868_x_at,1452465_at,1427520_a 3 0.9 1.3 2.2 1.9 _at,1427867_at 110639 Prps2 1420638_at,1454843_at,1420637_at 0.2 -0.1 -0.2 -0.9 -0.7 15469 Prmt1 1452787_a_at 0.8 0.7 0.2 -0.9 -1.3 18720 Pip5k1a 1418144_a_at,1426009_a_at,1455191 1.8 1.6 2 1 1.2 _x_at,1435039_a_at 72962 Tymp #N/A 0000 0 11416 Slc33a1 1423621_a_at 0 -0.2 -0.2 -0.7 -1.2 20849 Stat4 1448713_at 1 0.7 4.1 5.9 7.5 66387 Nudt8 1450111_a_at -0.1 -0.3 -0.3 -1.1 -1.1 16179 Irak1 1448668_a_at,1438857_x_at,1438120 0.2 -0.2 -0.5 -0.9 0.3 _x_at,1460649_at 78925 Srd5a1 1438699_at,1431101_a_at,1454649_a 1.7 0.6 1.3 1 1.3 t 239134 Gucy1b2 #N/A 0000 0 22142 Tuba1a 1433584_at,1416128_at,1418884_x_a 0.1 -0.1 -0.4 0 0.5 t,1448232_x_at 15468 Prmt2 1437234_x_at,1416844_at 0.1 0 0.6 0.8 0.3 19063 Ppt1 1422468_at,1444884_at,1422467_at, 1.5 0.9 0.9 0.7 2.9 1420016_at,1420015_s_at 22793 Zyx 1438552_x_at,1417240_at 0 0.1 0.4 0.3 -0.2 77559 Agl 1429083_at,1431032_at,1431033_x_a -0.1 -0.1 -0.9 -1.3 -0.1 t 17128 Smad4 1422486_a_at,1422485_at,1422487_a 0 -0.1 -0.2 -0.4 0 t 22417 Wnt4 1441687_at,1450782_at 3 2.7 3.6 3.5 3 17882 Myh2 1425153_at 0.1 -2.1 -2.7 -2.8 -3 216148 Shc2 1437944_at,1438598_at,1441356_at 0.1 1.4 1 0.6 -0.3 66248 Alg5 1424160_at,1430854_at 0.2 0.2 1.3 0.2 -0.6 16404 Itga7 1418393_a_at -0.3 -1.5 -1.9 -2.8 -1.2 56505 Ruvbl1 1416585_at -0.1 -0.1 -0.9 -1.5 -1 12491 Cd36 1423166_at,1450883_a_at,1450884_a 0 0 -0.1 -0.1 -0.5 t 14688 Gnb1 1417432_a_at,1454696_at,1425908_a 0 0.4 1.8 1 2 t 15006 H2-Q1 1431008_at,1451644_a_at 0.7 1.1 2.1 3 5.1 105

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 14672 Gna11 1449144_at,1434254_at 0.1 0.1 -0.2 0 0.3 224761 H2-M10.5 #N/A 0000 0 229363 Gmps 1455057_at,1433567_at,1435656_at 0.1 -0.3 -0.5 -1 -0.7 66979 Pole4 1432286_at,1423372_at,1423371_at 0.1 0.3 -0.1 -0.5 -0.6 16653 Kras 1451979_at,1426228_at,1434000_at, 0.3 1.1 0.4 -0.1 0.5 1426229_s_at 227231 Cps1 1455540_at 2.8 0.7 2.3 1.5 2.8 21415 Tcf7l1 1436207_at,1450117_at 2.7 2 2 0.6 0.9 26411 Map4k1 1439323_a_at -0.1 -0.3 -1.2 -1.6 -1.5 22411 Wnt11 1450772_at 0.3 0.2 0.4 0.8 0.4 14867 Gstm6 1422072_a_at 1.6 1.7 2.7 3.4 1 12633 Cflar 1424996_at,1449317_at,1425687_at, 0.9 2 2.3 3 2.3 1425686_at,1453482_at 109900 Asl 1448350_at -0.1 -0.1 -0.2 -0.5 -0.2 70584 Pak4 1428548_at 0 0 0 0.4 -0.2 14544 Gda 1435748_at,1435749_at,1422868_s_a 0.8 1.1 1.4 1.2 -0.1 t 66204 Acyp1 1421022_x_at,1450095_a_at,1439013 -0.1 -0.1 -0.5 -1.2 -1.1 _x_at 11529 Adh7 1450110_at,1421058_at 0.2 0.9 1.8 2.6 3 11532 Adh5 1443380_at,1416185_a_at 0.1 -0.1 0 0.4 0.3 22772 Zic2 1421301_at -2.7 -0.5 -1.7 -0.5 -0.5 20850 Stat5a 1421469_a_at,1450259_a_at 0.1 0.8 1 1.2 -0.6 16818 Lck 1439146_s_at,1457917_at,1439145_a 0.1 1.8 2.8 2.3 1.9 t,1425396_a_at 232087 Mat2a 1438386_x_at,1433576_at,1423667_a 0.2 -0.1 -0.8 -0.8 -0.7 t,1438630_x_at,1456702_x_at,143938 6_x_at,1438976_x_at 56458 Foxo1 1416981_at,1416982_at,1416983_s_a 0.3 0.6 0.7 0.5 1.5 t,1456529_at 15163 Hcls1 1418842_at 0.1 0.4 0.5 0.7 0.8 99571 Fgg 1416025_at -0.1 1 -0.7 -0.2 -1.8 272411 B3gnt6 1456680_at 0.7 0.3 0.8 0.2 0.6 64059 Oxct2a 1418272_at -0.2 -0.2 -0.1 -1 0.8 18574 Pde1b 1449420_at 0.5 0.5 1 1.1 0.3 22173 Tyr 1456095_at,1417717_a_at,1448821_a 0.8 0.8 0.7 1 0.1 t 12567 Cdk4 1422439_a_at,1422441_x_at,1422440 -0.1 -0.4 -0.9 -1.6 -1.1 _at 16408 Itgal 1435560_at,1425367_at 0 0.2 0.2 -0.2 -1.1 16832 Ldhb 1434499_a_at,1455235_x_at,1448237 -0.2 -0.1 -0.4 -0.6 -0.4 _x_at,1416183_a_at 100042410 Gm16483 #N/A 0000 0 58205 Pdcd1lg2 1450290_at -0.1 -0.1 0.5 1.1 0.4 21336 Tacr1 1422282_at 0.4 0.4 0.4 1.9 0 319713 Ablim3 1434013_at -0.6 -2.9 0.1 0.3 0.4 18846 Plxna3 1420995_at,1420996_at -0.1 0.5 0.9 1 0.3 230577 Pars2 1427309_at 0 -0.1 -1.4 0.2 0.1 106

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 18706 Pik3ca 1440054_at,1453134_at,1460326_at, 0.3 0.9 0 0.4 0.2 1423144_at,1429434_at,1429435_x_a t 21812 Tgfbr1 1420894_at,1420893_a_at,1420895_a -0.1 -0.9 -1.1 -1.3 -0.6 t 14377 G6pc 1417880_at 0.1 1 0.2 0.1 0.4 11836 Araf 1435566_s_at,1426602_at,1440764_a 0.1 -0.1 -0.1 -0.3 0 t,1428607_at,1445693_at 114663 Impa2 1418665_at,1459983_at 0 -0.1 -0.6 -0.6 0.3 74419 Tktl2 1430434_at 0.3 1.5 0.5 0.6 0.3 54485 Dll4 1421827_at,1421826_at 0 0 0.7 1.4 -1.3 15564 Htr5b 1422196_at 0.9 3.6 2.5 0.4 0.9 77626 Smpd4 1453182_a_at,1429530_a_at,1429531 0.2 0.2 0.2 -0.2 -0.3 _at,1437024_at 18718 Pip4k2a 1449404_at,1419279_at,1419280_at, 0.2 -0.1 0 0.1 0.5 1442310_at 246277 Csad 1427981_a_at 0.1 -0.5 -0.2 -0.1 0 67296 Socs4 1421273_at,1421275_s_at,1455142_a 0.1 0.1 0.2 0.1 0.4 t,1421274_at 240853 Gm4953 #N/A 0000 0 11975 Atp6v0a1 1460650_at,1425227_a_at,1459924_a 0.8 0.9 0.9 0.4 1 t,1417632_at 108079 Prkaa2 1429463_at,1429464_at 0.6 0.3 0.9 -0.5 0.9 54712 Plxnc1 1423214_at,1443433_at,1450905_at, 0 1.1 0.1 0.6 1.2 1423213_at,1450906_at,1443434_s_a t 170768 Pfkfb3 1416432_at,1456676_a_at -0.3 -0.4 0 0.9 1.5 216869 Arrb2 1451987_at,1426239_s_at 0.2 -0.3 -0.6 -1 -0.1 53357 Pla2g6 1431278_s_at,1431277_at,1422147_a 0 0.2 0.2 0.4 -0.1 _at 22152 Tubb3 1415978_at 0.8 -0.9 -1.4 -0.1 0.9 11540 Adora2a 1427519_at,1460710_at 1.8 2.8 3 3.1 1.8 21354 Tap1 1416016_at,1449803_x_at,1448177_a 0.5 1.7 2.8 3.4 3.2 t,1420274_at 242653 Cldn19 1425727_at 0.3 0.2 -0.1 2.5 0.9 14964 H2-D1 1424948_x_at,1425545_x_at,1427651 0.8 3.5 1 3.4 3.5 _x_at,1427726_at,1452547_s_at,1425 614_x_at,1426324_at,1452548_x_at,1 451934_at,1450170_x_at,1451683_x_ at,1452544_x_at,1451784_x_at

14599 Gh 1437522_x_at,1460613_x_at,1456595 0.3 0.4 3.2 0.5 1.6 _x_at,1460310_a_at 68738 Acss1 1437582_at,1437583_x_at,1416617_a 0.4 0.2 1.2 2.1 2.6 t 18538 Pcna 1417947_at 0 0 0.1 0.2 -0.1 16801 Arhgef1 1421164_a_at,1440403_at 0.2 -0.1 -0.5 -0.6 -0.1 66491 Polr2l 1428296_at -0.1 -0.1 -0.4 -1.1 -1.2 24064 Spry2 1421656_at,1436584_at 0.8 1 1.3 0.4 -0.2 19012 Ppap2a 1425449_at,1422620_s_at,1422619_a 1 -0.1 0.9 1.2 1.2 t 107

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 68428 Steap3 1430355_a_at,1423468_at,1453498_x -0.1 0.5 -0.4 -0.6 0 _at 57913 Lrdd 1421397_a_at -0.2 -0.1 -0.4 -0.3 -0.6 211488 Ado 1438484_at,1442133_at,1435923_at, 0 -0.1 0.5 0.5 0.8 1442135_at 11944 Atp4a 1421286_a_at 0.9 1.3 1 0.3 -0.4 226418 Yod1 1436976_a_at 0.2 -0.4 -0.7 -0.7 -1 18218 Dusp8 1418714_at 4.7 4.3 2.4 0 2.9 19713 Ret 1421359_at,1436359_at 0.1 -0.1 -0.7 0 -0.6 56419 Diap3 1422944_a_at 0.1 0.3 0.5 -4.2 -1.9 18576 Pde3b 1433694_at 0.3 -0.1 -0.4 -1 0.2 20112 Rps6ka2 1441311_at,1417543_at,1417542_at 0.2 0.1 0.1 0.9 0.8 14800 Gria2 1421970_a_at,1453098_at,1434146_a 1.7 1.2 0 1.4 2.3 t 19192 Psme3 1438509_at,1418078_at,1418079_at 0.8 0.6 0.5 1.1 -0.1 353325 Tas2r115 #N/A 0000 0 226519 Lamc1 1423885_at,1423886_at -0.2 0.1 -0.3 -0.6 -0.6 231637 Ssh1 1439237_a_at,1455854_a_at,1433874 0.2 0.3 0.4 1.2 2.2 _at,1438253_at 12291 Cacna1g 1423365_at -0.4 -0.8 -0.4 -0.1 -1.3 57370 B4galt3 1449435_at 0.1 -0.3 0.2 0.1 0.4 12409 Cbr2 1418509_at -1.6 -1.4 -0.3 -1 -2.2 68098 Rchy1 1432144_a_at 0 -0.2 -0.1 -0.2 0.2 54369 Nme6 1448574_at -0.5 -0.4 -1.2 -1.8 -0.7 14778 Gpx3 1449106_at -0.1 0 -0.2 0.1 -0.1 15245 Hhip 1421426_at,1455277_at,1438083_at, 3 2.9 2.5 1.9 2.5 1437933_at 230597 Zfyve9 1440348_at -0.1 -0.2 -0.7 0.1 -0.7 69718 Ipmk 1430031_at,1436215_at,1437856_at, 0 0.1 -0.2 -0.2 -0.3 1456200_at 242705 E2f2 1436434_at,1455790_at 0.4 -0.6 -0.4 -2.5 -0.6 29869 Ulk2 1417847_at,1448858_at,1417846_at, 0.3 0.1 -0.2 -0.4 0.2 1439591_at 18591 Pdgfb 1450414_at,1450413_at 0.1 -0.2 -0.2 -0.1 -0.3 14060 F13b 1419131_at 1 -2.3 -2.1 -1.6 -2 20377 Sfrp1 1448395_at,1428136_at,1416594_at, 1.1 2 1.5 1.7 0.7 1438620_x_at,1460187_at 19123 Proc 1418845_at 3.5 -0.1 1.8 0.2 2.1 13043 Cttn 1421313_s_at,1423917_a_at,1421314 1.2 0.9 3.5 1.7 0.2 _at,1421315_s_at,1433908_a_at 19895 Rpia 1418337_at 0 -0.3 -0.3 -0.9 -0.5 12388 Ctnnd1 1445830_at,1437448_s_at,1422450_a 0.4 0.2 -0.2 -0.4 0.2 t 12825 Col3a1 1427884_at,1427883_a_at 1.3 1.3 0.3 0.9 0.3 227671 Gbgt1 1426148_at -0.3 -0.4 0.5 0.8 -0.3 27374 Prmt5 1427439_s_at 0 -0.4 -1.2 -2.2 -0.7 433256 Acsl5 1428082_at -0.1 -0.1 0 -0.4 0.2 108

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 15965 Ifna2 1422403_at,1422404_x_at,1423028_a 3.1 1.2 7.9 5.9 2.6 t 14633 Gli2 1446086_s_at,1459211_at 2.4 0.6 0 1.6 1.6 433182 Gm5506 1427404_x_at,1419022_a_at,1431111 3.1 2.8 3.7 1.6 2.2 _at,1432829_at 14013 Mecom 1438325_at,1423011_at 1.4 0.3 0.4 0.2 0.8 21824 Thbd 1448529_at 0.5 0.5 0 -0.4 0.4 15109 Hal 1418645_at 0.5 -0.1 0.3 0.6 -0.6 11565 Adssl1 1449383_at -0.1 -0.2 -0.4 -0.9 0.8 66355 Gmpr 1448530_at -0.2 -0.9 -1.1 -1.6 -1.4 14782 Gsr 1421817_at 0 0.1 0.1 -0.7 -0.8 12566 Cdk2 1447617_at,1416873_a_at 0.1 2.7 5.3 0.4 0.7 234664 Nae1 1423781_at 0 -0.2 0 -0.4 -0.3 72293 Nkd2 1434275_at,1419465_at,1419466_at, 0.8 1 0.9 0.8 0.3 1457600_x_at 14732 Gpam 1419499_at,1425834_a_at 2.3 1.4 1.1 1.6 1.4 12503 Cd247 1426079_at,1426396_at,1420716_at, 2.8 3.7 2.8 4.3 1.9 1452539_a_at 103149 Upb1 1460244_at 0.1 0.6 1.5 0.3 3.8 20351 Sema4a 1438934_x_at,1448110_at 0 0 0.4 0.6 0.2 387355 Tas2r130 #N/A 0000 0 60597 Mapk8ip2 1449225_a_at,1435045_s_at,1455194 0.5 1.3 0.9 0.9 1.3 _at,1418786_at,1418785_at 53859 Map3k14 1422999_at,1434364_at -0.1 0 0 0.4 1.1 110695 Aldh7a1 1448137_at,1460167_at,1415902_at 0 0.1 0.1 0 0.2 16324 Inhbb 1426858_at,1426859_at -0.4 -0.3 0.8 1.8 0 17869 Myc 1424942_a_at -0.3 -1.2 -0.6 -1.6 -2 16833 Ldhc 1415847_at,1415846_a_at -0.2 0.4 1.1 0.5 0.3 19090 Prkdc 1451576_at 0 -0.4 -0.7 -0.8 -5.2 55936 Ctps2 1448111_at,1435759_at 0.1 0 -0.2 -0.4 -0.3 15205 Hes1 1418102_at 0.3 0.2 0 -0.1 -1.6 320452 P4ha3 1446951_at -1.8 -1.5 -3.1 -1.2 -0.8 12526 Cd8b1 1426170_a_at -0.7 -1.2 1.2 -0.6 -2.1 21943 Tnfsf11 1419083_at,1451944_a_at 0.1 2.1 0.5 0.9 1.5 21871 Atp6v0a2 1449870_a_at,1424513_at,1434791_a -0.1 -0.2 0.5 0.3 -0.2 t 103963 Rpn1 1448353_x_at,1456438_x_at,1439257 0.1 0 -0.2 -0.7 -0.8 _x_at,1438943_x_at,1416470_a_at

68292 Stt3b 1426342_at,1426343_at,1431541_at -0.1 -0.1 0.1 1.5 0.4 26921 Map4k4 1440609_at,1434184_s_at,1422615_a 0.7 1 0.7 0.6 0.7 t,1448050_s_at,1459912_at 69634 Clybl 1421014_a_at -0.1 0 -0.2 -0.8 -0.5 16848 Lfng 1449943_at,1420643_at 0.7 0.5 0 0.1 0.2 16775 Lama4 1424808_at,1424807_at -0.3 0.2 0.3 0.6 3.2 269180 Inpp4a 1421360_at,1436616_at 0.6 0.6 0.4 0.9 0 243764 Chrm2 #N/A 0000 0 109

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 13498 Atn1 1421149_a_at 0.3 0.3 0.2 0.4 0.8 19116 Prlr 1451850_at,1448556_at,1451844_at, 2.9 2.5 2.4 0.7 1.8 1421382_at,1450226_at,1441102_at, 1425853_s_at,1437397_at 13178 Dck 1428838_a_at,1439012_a_at,1449176 -0.2 0.8 1.7 1.4 0.8 _a_at 17532 Mras 1453419_at,1449590_a_at 0.2 -0.1 -0.5 -0.5 0 238463 Tubal3 #N/A 0000 0 14863 Gstm2 1416411_at -0.1 0.1 0.3 0.5 1 21898 Tlr4 1430695_at,1418162_at,1442827_at, 0.2 0.1 0.1 -0.1 -0.3 1418163_at 14687 Gnaz 1426517_at -0.7 -0.3 0.3 0 2.4 12297 Cacnb3 1448656_at 0.8 0.9 2 3.1 2.7 20135 Rrm2 1434437_x_at,1448226_at,1416120_a 0.1 0.1 -0.9 -2.9 -3 t 110094 Phka2 1437941_at,1434518_at,1430492_at 0 -0.1 0 -0.5 -0.8 100163 Pafah2 1448489_at 0 -0.3 -0.6 -1.8 -1.3 67951 Tubb6 1416431_at,1446353_at -0.2 -0.4 -0.2 0.5 0.6 12426 Cckbr 1454770_at,1460663_at 0.3 0.8 0.1 0.5 0.2 18035 Nfkbia 1438157_s_at,1448306_at,1420088_a 1.3 0.9 1.3 1.5 -0.1 t,1420089_at,1449731_s_at 17000 Ltbr 1416435_at 0 -0.1 -0.1 -0.2 0.4 54128 Pmm2 1431464_a_at,1431938_a_at,1439953 0 0.1 0.1 0.1 0.6 _at 18976 Pomc 1455858_x_at,1433800_a_at 0.1 0.6 0.6 1.1 0.8 235611 Plxnb1 1435255_at,1435254_at 0.1 0.2 0.5 0.5 0 17161 Maoa 1442676_at,1428667_at 0.6 0.1 0 0.1 0.2 13808 Eno3 1417951_at 0.2 0 0 -0.3 -0.5 13614 Edn1 1451924_a_at 0.4 0.9 1.7 2 -1.2 14313 Fst 1421365_at,1434458_at 0.7 1.2 0.3 -0.4 -1.8 12450 Ccng1 1450016_at,1450017_at,1420827_a_a -0.2 -0.2 -0.4 -0.7 -0.9 t 13040 Ctss 1448591_at 0.1 0 0.2 0.3 0.4 16797 Lat 1460651_at -0.1 -0.2 -0.4 -0.5 -0.8 23928 Lamc3 1425594_at,1451758_at -0.6 0.9 -0.1 -0.5 -0.8 81897 Tlr9 1422083_at 0 0 0.2 0.5 0.5 54377 Cacng4 1450975_at 1.4 0.8 -0.1 0.6 0 104418 Dgkz 1446614_at,1426738_at,1452169_a_a 0.2 -0.1 -0.4 0.1 0.4 t 12763 Cmah 1436039_at,1447019_at,1421214_at, 0.9 4.3 3.1 2.9 3.3 1440517_x_at,1440458_at,1428043_a _at 12334 Capn2 1416257_at -0.2 -0.3 -0.5 -0.3 0.1 57257 Vav3 1417122_at,1417123_at,1448600_s_a 0.3 -0.1 0.2 -0.2 -0.2 t 26459 Slc27a5 1449112_at 0.9 0.6 -0.6 0.3 -3 18430 Oxtr 1440888_at,1426000_at -1.1 0.6 1 2 -1.1 12622 Cer1 1450256_at,1450257_at 0.1 0.8 0.2 0.3 0.7 110

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 53332 Mtmr1 1421879_at,1421880_at -0.1 0 -0.2 -0.6 -0.1 353165 Tas2r136 #N/A 0000 0 26904 Sh2d1b1 1423024_at -0.2 -0.7 -1.3 -2.2 -0.7 108156 Mthfd1 1436704_x_at,1415916_a_at,1415917 0 -0.2 -1 -2.2 -2.2 _at 11992 Auh 1458436_at,1445496_at,1420776_a_a 1.5 0.4 0.4 0.5 1.2 t,1431124_at,1430487_at,1447952_at

106648 Cyp4f15 1449316_at -2.7 -1.9 -1.7 0.1 -2.2 105014 Rdh14 1453864_at,1417438_at,1457019_s_a 0 -0.2 -0.1 0.8 0.3 t 236899 Pcyt1b 1437648_at,1436124_at 3 0.1 2.8 3.7 3.1 11847 Arg2 1438841_s_at,1418847_at 0.2 0.4 0 -0.8 -2.6 22324 Vav1 1422932_a_at 0 0.1 0.3 0.3 0 18645 Pfn2 1418209_a_at,1436993_x_at,1418210 0.3 -0.4 -0.4 -0.2 0 _at 13070 Cyp11a1 1448804_at,1439947_at,1457604_x_a -0.1 1.3 4.4 2.8 0.7 t 93742 Pard3 1436765_at,1434775_at,1420391_at, 2.2 3.5 0.4 0.9 1.3 1436764_at 18021 Nfatc3 1452497_a_at,1419976_s_at -0.2 -0.3 -0.6 -0.8 -0.4 19766 Ripk1 1419508_at,1449485_at,1439273_at 0 0 0.1 0.1 0.5 22045 Trhr 1449572_at,1449571_at 2.5 2.5 5.6 5.2 4.1 236082 Dhrsx 1456484_at -0.9 -1.5 -0.4 -0.4 -0.5 54124 Cks1b 1448441_at,1416698_a_at 0 -0.1 -0.4 -2.2 -2.7 56443 Arpc1a 1416079_a_at -0.1 -0.2 -0.3 -0.3 0.3 70223 Nars 1452866_at,1428666_at 0 0 -0.2 -0.5 0.2 114716 Spred2 1423001_at,1441802_at,1436892_at, 0.2 -0.2 -0.3 -0.6 0.5 1434403_at 268656 Sptlc1 1422691_at,1436726_s_at,1422690_a 0.1 0.4 0.4 0 0.6 t,1436727_x_at 378435 Mafa #N/A 0000 0 66375 Dhrs7 1426440_at,1432892_at,1432891_at 1.3 1.2 0.8 0.8 0.4 99890 Prmt6 1425059_at,1434209_at 0.2 -0.1 -0.6 -0.2 0.8 11352 Abl2 1455682_at,1445483_at,1455495_at -0.1 0 -0.2 -0.3 0.7 13478 Dpagt1 1448549_a_at -0.2 -0.2 -0.7 -1.2 -0.4 212032 Hk3 1435490_at,1442798_x_at 0.1 0.1 0.7 1.4 1.3 11475 Acta2 1416454_s_at,1444105_at,1456658_a 1.5 2.3 1 3 -0.3 t 13347 Dffa 1450885_at,1457564_at 0.3 0.1 0.8 0.4 0.4 12452 Ccng2 1448364_at,1416488_at 0.4 1.6 1.7 2.2 1.4 11637 Ak2 1448450_at,1448451_at 0.1 0 -0.2 -0.1 0.1 17444 Grap2 1460280_at,1456432_at,1420685_at 0.6 0.4 0.6 0.6 0.1 20905 Sts 1421500_at 0 -0.2 -0.2 -0.2 0.9 27373 Csnk1e 1417176_at,1417175_at,1435373_at 0 -0.3 -0.1 -0.4 -0.4 66237 Atp6v1g2 1417799_at 0.2 0 0 -0.5 -0.2 18439 P2rx7 1419853_a_at,1439787_at,1422218_a 0.1 -0.1 0.2 0.6 1.1 t 111

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 15445 Hpd 1424618_at -1.1 -0.2 -1.3 -1 -0.8 56318 Acpp 1453943_a_at,1419832_s_at,1441975 0 1 1.3 1.9 1.1 _at 103850 Nt5m 1453767_a_at -0.1 -0.3 -0.4 -0.3 0.4 11423 Ache 1422635_at -1.1 0.8 1.2 2.8 1.7 16638 Klra7 1426171_x_at,1451664_x_at 1.9 0.5 0.7 1.3 -0.7 192113 Atp12a 1449475_at 0.1 -2.1 -2.3 -0.6 -2.7 71990 Ddx54 1438853_x_at,1447882_x_at,1460396 0 0 -0.3 -0.1 -0.3 _at 12314 Calm2 1417366_s_at,1450864_at,1422414_a 0.2 0.2 0.2 0.7 0.8 _at,1423807_a_at 15376 Foxa2 1422833_at -0.1 0.2 0.3 2 -0.4 11350 Abl1 1441291_at,1444134_at,1423999_at 0.2 0.5 0.1 -0.7 0.4 387342 Tas2r107 #N/A 0000 0 15360 Hmgcs2 1431833_a_at,1423858_a_at 0.6 0.7 0.2 0.8 -1.1 225825 Cd226 1445388_at 0.2 -0.7 -0.6 1.4 -0.2 20322 Sord 1438183_x_at,1426584_a_at 0 -0.2 -0.1 -0.3 0.5 64058 Perp 1416271_at -0.3 -2.3 0.5 0.7 0.4 85305 Kars 1416068_at -0.2 -0.1 -0.1 0.2 -0.1 52432 Ppp2r2d 1420033_s_at,1420034_at,1424527_a 0.4 0.2 0.3 0.2 0.2 t 17305 Mfng 1416992_at 0 0.2 -0.6 -0.2 0.8 12649 Chek1 1450677_at,1420031_at,1439208_at, 0.3 2.8 1.1 0.8 0.7 1420032_at,1449708_s_at 53892 Ppm1d 1449092_at,1434142_at 0 -0.2 -0.2 -0.2 -0.2 18795 Plcb1 1421170_a_at,1425782_at,1425781_a 0.8 1 1.4 1.2 1 _at,1425600_a_at,1435043_at 19141 Lgmn 1448883_at -0.2 -0.3 -0.4 -0.1 0.5 16822 Lcp2 1418642_at,1418641_at 0 0.5 0.3 0.4 -0.7 16195 Il6st 1437303_at,1421239_at,1452843_at, -0.1 -0.2 -0.3 -0.6 0.1 1460295_s_at 12300 Cacng2 1453363_at,1440210_at,1420596_at 1.7 2.6 0.3 1.3 2.3 12908 Crat 1448544_at,1441919_x_at,1417008_a 0 0.1 -0.3 0 -0.5 t 14081 Acsl1 1447355_at,1423883_at,1460316_at, 0.1 1.2 2.3 3.3 1.9 1450643_s_at,1422526_at 71679 Atp5h 1435112_a_at,1423676_at 0.1 0.1 0 -0.1 -0.2 56468 Socs5 1423350_at,1423349_at 0.2 0.2 0 -0.3 -0.3 18034 Nfkb2 1425902_a_at,1429128_x_at 0.8 0.8 0.7 1.3 0.1 13163 Daxx 1419026_at 0.2 2.3 2.9 3.1 2.7 12444 Ccnd2 1416123_at,1434745_at,1448229_s_a 0.2 1.4 2.8 3.5 1.7 t,1416124_at,1416122_at,1455956_x_ at,1430127_a_at 12323 Camk2b 1448676_at 0 -0.8 -0.8 -0.2 -1.2 140483 Hnmt 1417702_a_at -0.1 -0.4 -1.3 -1.9 -1.6 17252 Rdh11 1449209_a_at,1418760_at 0 0.1 -0.5 -0.5 -0.4 14187 Akr1b8 1448894_at -0.1 0 -0.2 -0.6 0.2 57252 Tas2r105 1422389_at 0 -0.3 -0.4 0.1 -3.4 112

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 74551 Pck2 1425615_a_at,1452620_at 0 0 0.2 -0.3 0.2 216739 Acsl6 1451257_at,1437031_at 2.1 0.2 1.3 1.2 2.2 12845 Comp 1419527_at -0.1 0 0.4 0.4 -0.7 67374 Jam2 1436568_at,1431416_a_at,1449408_a 1.1 0.6 2.4 4 1.4 t,1431417_at,1419288_at 215446 Entpd3 1434049_at 0.9 0.6 0.6 0.4 0.8 233649 Cnga4 1445339_at -0.6 0.1 -1 0.3 2 11689 Alox5 1441962_at 0 0 -0.1 -1.7 -1.8 13106 Cyp2e1 1415994_at -0.1 -2.2 -0.2 0.1 -0.5 14131 Fcgr3 1448620_at 0 -0.2 -0.3 -0.4 0.1 19079 Prkab1 1424119_at,1452457_a_at -0.1 -0.6 -0.3 -0.3 0.5 18438 P2rx4 1441772_at,1446429_at,1452527_a_a 0.3 0.3 1 1 1.6 t,1425525_a_at 27369 Dguok 1425228_a_at -0.3 -0.3 0.1 0.2 0.3 11556 Adrb3 1455918_at,1421555_at 0.9 0.7 0.3 0.9 1.7 229709 Ahcyl1 1426831_at,1425576_at,1426830_a_a 0 -0.1 0.1 0.1 0.7 t 384783 Irs2 1443969_at -1.2 -3.1 -1.9 -3.6 -1.6 14183 Fgfr2 1420847_a_at,1433489_s_at 2.7 3.2 3 1.6 1.5 22029 Traf1 1445452_at,1423602_at 1.2 0.6 1.5 2 1.4 56357 Ivd 1449001_at,1418238_at -0.1 -0.1 -0.5 -0.8 0.1 50790 Acsl4 1418911_s_at,1451828_a_at,1433531 0.1 0.1 0.4 0.5 0.4 _at 16438 Itpr1 1417279_at,1460203_at -0.1 -0.1 2.5 3 1.5 14651 Hagh 1424172_at,1437519_x_at,1424171_a 0.2 0 -0.2 -0.8 -0.9 _at 338375 Atp6v1g3 #N/A 0000 0 12737 Cldn1 1438850_at,1437932_a_at,1450014_a 0.5 0.3 0.9 -0.5 0.7 t,1438851_x_at 382985 Rrm2b 1437222_x_at,1433773_at,1437221_a 0.4 0.1 0.7 0.1 0.1 t,1437476_at 11482 Acvrl1 1451604_a_at,1435825_at -0.2 -0.3 -0.5 -0.5 -0.9 20111 Rps6ka1 1416896_at -0.1 -0.3 -0.7 -0.7 -0.5 56348 Hsd17b12 1450011_at,1450010_at 0.2 0.2 0.3 -0.1 0 93840 Vangl2 1436118_at,1419218_at,1455592_at 0.9 0.5 0 0.1 -1.1 14695 Gnb3 1449159_at -0.3 0.2 -0.2 0.1 0.5 67771 Arpc5 1448129_at,1444568_at 0 0 0.3 0.1 -0.1 66354 Snw1 1429003_at,1429002_at 0 0.1 0.5 0.9 1.6 107986 Ddb2 1436680_s_at,1425706_a_at 0.4 0.1 0.1 0.3 0.7 14999 H2-DMb1 1449580_s_at,1418638_at 0 0 0.1 0.1 -0.3 18440 P2rx6 1450327_at,1456925_at 0.8 0.4 0.2 0.4 1.2 19684 Rdx 1448236_at,1416179_a_at,1416180_a 0 0 -0.2 -0.4 -0.2 _at 269587 Epb4.1 1430369_at,1424092_at,1458807_at, 0.3 0 -0.3 -0.3 0.2 1444150_at 14609 Gja1 1415801_at,1438973_x_at,1415800_a 1 2.3 1.7 0.9 0.7 t,1438650_x_at,1437992_x_at,143894 5_x_at 113

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 13107 Cyp2f2 1448792_a_at 0.1 -2.4 0.3 -0.4 0.4 15565 Htr6 1421757_at 0.3 0.9 1 0.6 -0.3 22436 Xdh 1451006_at -1.3 -1.2 -0.4 1.3 2.4 108058 Camk2d 1439168_at,1459457_at,1460630_at, 0.6 0.8 1.2 0.9 0.9 1427763_a_at,1456844_at,1444031_a t,1422659_at 66904 Pccb 1450969_at 0 -0.1 -0.5 -1.5 -1.8 101809 Spred3 1435852_at -1.9 -3.2 -2.8 0.4 0.2 217837 Itpk1 1426733_at,1431823_at 0.2 0 0 0.1 0 14571 Gpd2 1452741_s_at,1428323_at,1417434_a 0.2 0.6 0.7 1 -0.3 t 13206 Ddx4 1427242_at -1.6 1 2.8 4.3 2.8 71974 Prmt3 1442719_at,1454008_at,1431768_a_a 0.4 0.5 0.1 -1.2 -0.2 t,1457332_at,1426749_at 14205 Figf 1449528_at,1438954_x_at,1438953_a 0.6 0.8 2.5 0.4 2.7 t 15945 Cxcl10 1418930_at 4.6 7.7 8 8.2 5.7 110074 Dut 1419269_at,1419270_a_at -0.1 -0.2 -0.7 -1 -0.4 12912 Creb1 1423402_at,1452901_at,1428755_at, 3.4 0.5 1.3 3.1 2.5 1421582_a_at,1452529_a_at,1421583 _at 93672 Il24 1426181_a_at 0.1 2.3 2.9 3 3.5 11477 Acvr1 1448460_at,1416786_at,1416787_at 0.2 0.4 0.7 0.5 -0.1 56217 Mpp5 1450113_at,1421064_at,1434954_at 0.2 0.3 0.2 0.4 0.5 80908 Abo 1421559_at -3.6 -1.4 -2.8 -2.1 -3.6 208677 Creb3l3 1424688_at -1.7 0.5 -0.3 1.2 0.3 11550 Adra1d #N/A 0000 0 68652 Tab2 1423462_at,1451003_at -0.1 0.2 0.4 0.5 0.2 12487 Cd28 1417597_at,1443703_at,1437025_at 1.6 0.8 1 -0.4 1.2 108682 Gpt2 1439029_at,1438385_s_at,1455007_s 0 -0.1 0.2 0.3 0 _at,1434542_at 16185 Il2rb 1448759_at,1417546_at 0.6 0.9 0.7 1.6 1.1 22330 Vcl 1416156_at,1416157_at -0.2 0 0.5 0.2 -0.9 387349 Tas2r121 #N/A 0000 0 15200 Hbegf 1418350_at,1418349_at 0.6 0.9 1.7 2.2 0.2 68603 Pmvk 1427893_a_at 0 0.1 -0.1 0.2 0.3 213119 Itga10 1440235_at -0.9 -1.2 -0.4 -3 -1 22144 Tuba3a 1416311_s_at,1448296_x_at 0 -0.5 -0.7 -0.7 0.1 16325 Inhbc 1422001_at 1.3 0.6 1.7 0.8 0.2 11997 Akr1b7 1423556_at -0.2 -0.1 -2 -0.9 -2.7 14062 F2r 1437308_s_at,1450852_s_at 0.4 -0.2 0.3 0.4 -1.4 74198 Dtx2 1439429_x_at,1421720_a_at -0.1 -0.1 0.5 0.6 0.2 14998 H2-DMa 1422527_at,1459872_x_at 0 0.1 -0.2 -0.2 -0.8 11789 Apc 1435543_at,1450056_at,1420957_at, 0.1 -0.1 -0.2 -0.3 -0.2 1420956_at 15251 Hif1a 1416035_at,1431981_at,1448183_a_a 0.9 0.4 1.5 2.1 1.2 t,1427418_a_at 114

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 394434 Ugt1a9 1424783_a_at,1426261_s_at,1426260 -0.1 0.2 -0.1 -0.3 0.7 _a_at 27425 Atp5l 1448203_at 0.2 0.1 0.1 0 -0.3 19076 Prim2 1418036_at,1418035_a_at,1445474_a 0.2 0.3 0.4 0.9 1.9 t 15559 Htr2b 1422125_at 0 -1.5 0.1 1.5 3.8 14933 Gyk 1445242_at,1422704_at,1422703_at 0 0.3 -0.1 0.3 -0.2 239017 Ogdhl #N/A 0000 0 56375 B4galt4 1425934_a_at -0.6 -1.9 1.2 1.1 -0.4 56808 Cacna2d2 1426185_at,1450754_at,1451955_a_a -0.3 2.1 0.6 1.7 0.4 t 18383 Tnfrsf11b 1418309_at,1449033_at -0.3 -0.5 0.9 1 0.4 12443 Ccnd1 1417419_at,1448698_at,1417420_at 0 0.1 1.8 2.1 1.6 21356 Tapbp 1450378_at,1421812_at -0.1 0.4 1.1 1.7 1.4 14660 Gls 1434657_at,1457211_at,1436299_at, 0 0.1 0.4 1.3 0.4 1438827_at 16160 Il12b 1449497_at,1419530_at 3.5 3.9 4.3 5.7 3.5 15465 Hrh1 1419210_at,1438494_at -0.2 -0.1 0 0.8 0.7 16542 Kdr 1449379_at 0.2 0.7 2.7 3.5 4 20865 C730007P1 1419528_at -1.2 -0.8 -1.1 -1.2 -1.8 9Rik 12814 Col11a1 1449154_at,1418599_at 0.5 1.4 1.8 3.8 4.7 14632 Gli1 1449058_at -0.2 -0.5 -0.2 -1 -0.9 17025 Alad 1424877_a_at -0.2 -0.5 -1.7 -1.6 -0.8 83961 Nrg4 1421681_at,1457123_at -0.2 0.6 0.1 1.1 2 22147 Tuba3b 1416311_s_at,1448296_x_at 0 -0.5 -0.7 -0.7 0.1 114713 Rasa2 1455181_at,1422785_at 0.3 0.6 0.1 0.2 -0.1 16423 Cd47 1430997_at,1449507_a_at,1428187_a 0.3 0.8 1.5 1.9 2.1 t,1419554_at 76089 Rapgef2 1452833_at 0 1.5 2.4 2.9 1.5 13363 Dhh 1434959_at,1422127_at 0.3 0.5 0.6 0.3 0.8 15980 Ifngr2 1423558_at,1423557_at 0.1 0.1 0.5 0.7 0.8 22350 Ezr 1450850_at,1456725_x_at -0.1 -0.1 -0.6 -0.4 -0.3 434437 Amt #N/A 0000 0 58235 Pvrl1 1438421_at,1438111_at,1450819_at 0.9 1.1 2.1 1.5 2 72269 Cda 1427357_at -0.3 0.2 0.2 -0.8 -0.3 12606 Cebpa 1418982_at -0.5 -1.2 -1.2 -1.6 0.2 13361 Dhfr 1430750_at,1419172_at -0.2 0.2 -0.4 0 -2 54612 Sfrp5 1436075_at,1423023_at 0.3 0.7 0 0 -2.1 20352 Sema4b 1455678_at,1427586_at 0.3 0.3 0.2 0.5 2 55994 Smad9 1450265_at 0.4 0 -0.4 2 -0.6 13389 Dll3 1449236_at -0.3 -0.3 0.6 0 0.1 14254 Flt1 1454037_a_at,1451756_at,1440926_a 0.1 -0.3 -0.6 0.3 -1.4 t,1419300_at 14417 Gad2 1421978_at,1429589_at 2.1 0 0.8 1.8 1.6 17706 ATP8 #N/A 0000 0 115

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 13649 Egfr 1460420_a_at,1432647_at,1424932_a 2.5 2.5 0.5 0.5 1.5 t,1454313_at,1457563_at,1451530_at ,1435888_at 19241 Tmsb4x 1415906_at 0.2 0 0.2 0.3 0.3 12234 Btrc 1457305_at,1417325_at,1443142_at, 0.9 0.4 0.8 1.4 1.5 1446925_at,1425680_a_at 19286 Pts 1450660_at,1458402_at 0.2 0.1 0 -0.6 -0.9 14348 Fut9 1457409_at,1435308_at,1450771_at 0.3 -0.3 0.2 1.3 1.1 11958 Atp5k 1434053_x_at,1450640_x_at,1422525 0.2 0 0.1 -0.2 -0.4 _at 231050 Galnt11 1424748_at,1432840_at 0.3 2 0.1 2 1 11650 Alppl2 1450636_s_at,1450635_at -0.1 0.2 -0.2 0.2 0.1 15159 Hccs 1420889_at,1420890_at 0.2 -0.2 -0.4 -0.8 -0.6 268591 Serpina5 1418813_at -1.5 -1.9 -2.4 -2 -1.5 241391 Galnt5 #N/A 0000 0 170732 Trhr2 1450356_at 0.1 0.4 0.3 0.3 0.1 11534 Adk 1446068_at,1421767_at,1449641_at, 1.4 0.8 0.9 0.5 -0.2 1446675_at,1416319_at,1438292_x_a t 12914 Crebbp 1434633_at,1459804_at,1435224_at, 0.2 2.5 0.3 2.1 0.1 1436983_at 23871 Ets1 1452163_at,1422028_a_at,1422027_a 0.1 -0.3 -0.1 -0.2 -0.8 _at,1426725_s_at 13367 Diap1 1445391_at,1454979_at,1421143_at 0.2 -0.1 -0.1 -0.2 0.1 97541 Qars 1456726_x_at,1423712_a_at,1456213 0.3 -0.1 0.2 -0.2 0.3 _x_at,1453237_at 20969 Sdc1 1448158_at,1415943_at,1415944_at, 0 -0.2 -0.5 0.3 2.5 1437279_x_at 14369 Fzd7 1450044_at,1450043_at -0.2 0.2 0 0.4 1.2 270198 Pfkfb4 1456888_at -0.2 -0.7 -0.7 -0.7 0.8 26410 Map3k8 1419208_at 0.3 0.3 0.6 0.1 -0.9 72469 Plcd3 1431892_a_at 0.9 -1.4 1.5 1.6 1.6 54401 Ywhab 1436783_x_at,1420880_a_at,1420879 0.1 0.2 -0.1 0.2 0.4 _a_at,1455815_a_at,1438708_x_at,14 20878_a_at 140742 Sesn1 1444376_at,1433711_s_at,1438931_s -0.2 -0.9 -0.6 0.1 -0.9 _at,1454699_at 12832 Col5a2 1450625_at,1422437_at 3.7 0.5 0.7 1.3 0.7 18816 Serpinf2 1417498_at 0 -1 0.2 -3.7 -3.1 228550 Itpka 1424037_at -0.2 -0.5 0.4 0.4 0.7 18451 P4ha1 1452094_at,1426519_at -0.1 0 1 1.6 1.7 110446 Acat1 1451271_a_at,1424182_at,1424183_a 0 -0.2 -0.4 -1.6 -1.8 t 13030 Ctsb 1444987_at,1448732_at,1417491_at, 0.1 0 0.3 0.4 1.1 1417492_at,1417490_at 18948 Pnmt 1460269_at,1449804_at,1450606_at 1.5 2.6 2.8 3.3 2.4 15208 Hes5 1456010_x_at,1423146_at 2 -1.7 0.3 1 0.6 242669 Adc 1439649_at,1442093_at,1444585_at 2.2 1.8 0.5 2.1 0.3 18707 Pik3cd 1443798_at,1453281_at,1422992_s_a 1.6 1.7 1.5 0.9 -0.3 t,1422991_at,1458321_at 116

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 232449 Dera 1424047_at,1447431_at -0.2 -0.1 -0.2 0 0.1 12647 Chat 1440070_at 3.4 2.4 0.9 2 0.5 18749 Prkacb 1420611_at,1420610_at,1457197_at -0.2 0.7 0.5 0.8 0.3 20416 Shc1 1422853_at,1422854_at 0 -0.2 -0.3 -0.7 -0.4 214230 Pak6 1455200_at,1445475_at 0.3 1 -1.2 -1.4 -1.6 83553 Tktl1 1449567_at,1420065_at,1420064_s_a 1 2.5 0.9 0.9 3.7 t 12530 Cdc25a 1417132_at,1445995_at,1417131_at 0.1 -0.4 -1 -1.3 -0.6 23959 Nt5e 1422974_at,1459023_at,1428547_at 1.2 0 -0.1 -0.4 -0.6 22084 Tsc2 1452105_a_at -0.3 -0.1 -0.2 -0.3 0.1 11639 Ak3l1 1421829_at,1450387_s_at,1421830_a 0.5 0.4 -0.2 0.8 1.3 t 14370 Fzd8 1423348_at,1445815_at 0.2 0.2 0.3 2.2 0.1 78920 Dlst 1423710_at,1430161_at,1437775_at, 0.5 0.1 -0.3 -0.6 -0.1 1431011_at 19015 Ppard 1439797_at,1425703_at 0 0.2 0.1 0.1 1 11945 Atp4b 1448911_at 0.4 0.3 0 0.6 -0.4 13350 Dgat1 1418295_s_at,1445229_at 0.1 -0.1 -0.2 0 1.3 22415 Wnt3 1450763_x_at 0.5 0.4 2.1 2.3 0.4 14085 Fah 1417220_at 0.3 -1.2 -0.5 0.1 -0.2 67078 Pgp 1428788_at,1452919_a_at 0 -0.3 -1.1 -1 -0.1 15495 Hsd3b4 1417554_at 0.5 0.3 2.9 0.4 -0.2 53627 Porcn 1424220_a_at -0.1 -2.1 0.2 0 -0.7 15490 Hsd17b7 1417871_at,1457248_x_at,1448865_a 0.3 0.3 -0.1 0 0.4 t,1440057_at 11481 Acvr2b 1419140_at,1439856_at 0.1 0.1 -0.6 -0.5 -0.4 17850 Mut 1416839_at,1416838_at,1448486_at 0.6 1.8 -0.3 -0.5 1.4 15461 Hras1 1422407_s_at,1424132_at 0.2 -0.1 -0.3 -0.4 0.1 17295 Met 1422990_at,1434447_at -0.1 0.7 1.2 1.4 0.7 26374 Rfwd2 1426912_at -0.1 0 0 -0.3 -0.5 18044 Nfya 1422082_a_at,1452560_a_at,1427808 0.2 -0.2 0 -0.2 -0.2 _at 67512 Agpat2 1428821_at 0 0 0 -0.1 -0.2 18845 Plxna2 1455037_at,1451753_at,1453286_at, 0.9 1.5 0.8 1.2 1.5 1429772_at 19084 Prkar1a 1447635_at,1425550_a_at,1452032_a 1.3 0.7 1.1 1.5 0.8 t 11461 Actb 1419734_at,AFFX-b- 0.3 0.1 0.3 0.4 0.4 ActinMur/M12481_M_at,AFFX-b- ActinMur/M12481_3_at,AFFX-b- ActinMur/M12481_5_at,1436722_a_at

14629 Gclc 1424296_at,1455959_s_at -0.1 0.1 -0.3 -0.6 0.3 219135 Mtmr6 1425485_at,1425486_s_at,1456540_s 0.1 0.3 0.3 0.3 -0.1 _at,1451726_at 225028 Map4k3 1426759_at,1446798_at 0.2 -0.1 0.1 0.3 0.3 66513 Tab1 1447692_x_at,1426898_at 3.9 0.5 0.5 3.7 0.6 11465 Actg1 1415779_s_at 0.1 0.1 0.2 0.3 0.2 117

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 68180 Hyi 1425201_a_at 0.1 -0.2 -0.3 -0.5 0.4 20185 Ncor1 1435914_at,1444760_at,1423202_a_a 0.7 0 0.3 0.4 0.7 t,1423201_at,1458103_at,1423200_at

17126 Smad2 1420634_a_at 0 0.1 0.1 0.1 0 108989 Tpr 1456651_a_at,1426949_s_at,1426948 0.1 0.5 0.5 0.5 -0.1 _at,1456112_at 71773 Ugt2b1 1424934_at -0.1 -0.1 -0.6 0.1 0.3 12934 Dpysl2 1450502_at,1433770_at 0.8 0.5 0.6 0.9 0.4 14865 Gstm4 1424835_at -0.1 0 0.1 -0.1 0.5 213208 Il20rb 1437876_at 0.3 0.3 -0.1 0.6 -0.4 12672 Chrm4 1450575_at 0.6 0.5 -0.2 0.1 0 216795 Wnt9a 1436978_at,1425889_at -0.9 -0.1 0.6 0.1 0.1 14961 H2-Ab1 1425477_x_at,1450648_s_at,1451721 0 0.2 0.3 0.4 0.3 _a_at 18223 Numbl 1416491_at -1.5 -3.8 -1.3 -0.1 0 56492 Cldn18 1425445_a_at,1449428_at 0.7 1.1 0.2 1.3 0.3 228785 Mylk2 1427556_at -0.5 -0.6 0.4 0.1 -0.2 14969 H2-Eb1 1417025_at 0.1 0 0.1 0.3 0.4 12827 Col4a2 1424051_at 0.7 0.5 0.7 1.3 0.4 21414 Tcf7 1450461_at,1433471_at 0.5 1.3 0.4 0.4 -0.4 12005 Axin1 1426966_at,1426967_at 0 0.2 -0.1 -0.3 0.5 74129 Dmgdh 1452311_at 1.2 1.8 0.9 0.5 1.7 59004 Pias4 1440075_at,1455394_at,1418861_at 0.2 -0.1 0.1 0.4 0.3 12918 Crh 1457984_at -1.2 1.3 -1.8 -2.7 1.6 269181 Mgat4a 1444347_at,1435641_at 0 0.3 1.2 1.1 0.3 56421 Pfkp 1416069_at,1430634_a_at,1437759_a 0.7 0.4 0.9 0.9 0.1 t 75686 Nudt16 1439884_at,1421204_a_at 0.1 -0.2 0.1 0.3 0.9 12166 Bmpr1a 1425491_at,1425494_s_at,1451729_a 0.7 0.5 1.1 0.4 1 t,1425493_at,1445413_at,1425492_at

16000 Igf1 1434413_at,1452014_a_at,1419519_a 0000 -0.4 t,1437401_at 227095 Hibch 1451511_at,1451512_s_at -0.3 -0.1 -0.9 -1.9 0.1 72058 Igsf5 1451407_at 1.1 0.6 0.4 -0.5 0 76252 Atp6v0e2 1448211_at -0.3 -1 -2.7 -2.4 -2.9 21809 Tgfb3 1417455_at -1.9 -0.5 1.2 0.7 -0.7 14371 Fzd9 1427529_at 0.5 -0.7 -2.2 0.1 -0.5 17344 Pias2 1428725_at,1426456_a_at,1419454_x -0.1 -0.3 0 0.1 0 _at 15139 Hc 1419407_at 3.9 0.2 0.5 2.9 3 18260 Ocln 1448873_at 0.1 2.9 3.5 2.9 1.9 15108 Hsd17b10 1438391_x_at,1448286_at 0 0 -0.4 -1 -1.1 13839 Epha5 1420557_at,1435286_at,1437920_at, 3.4 2.4 1.3 2.1 1.6 1444690_at 19075 Prim1 1418369_at,1449061_a_at -0.1 -0.1 -0.8 -1.9 -2.3 118

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 30957 Mapk8ip3 1425975_a_at,1416437_a_at,1436676 0.3 0.2 -0.1 -0.2 1.3 _at 16992 Lta 1420353_at 0.5 1.1 1.2 2.4 0.2 16779 Lamb2 1416513_at -1.5 0.5 -0.8 -0.2 -1.1 16478 Jund 1449117_at,1455774_at,1440265_at 0.2 0.3 0.5 0.7 0.4 13382 Dld 1433263_at,1423159_at 0.1 0.1 0.9 -0.2 0.3 14776 Gpx2 1449279_at 0.1 -1.5 -1.2 -2.5 -0.9 433749 Gm12844 1450632_at -0.2 -0.1 -0.2 0.1 0 320632 Snrnp200 1454772_at,1460552_at -0.2 0.1 -0.2 -0.1 -0.3 213788 Chrm5 #N/A 0000 0 108902 B3gnt1 1452346_at -0.4 -0.6 0 -0.2 0.4 76952 Nt5c2 1448614_at,1417201_at,1425933_a_a -0.1 -0.1 -0.3 -0.8 -0.7 t 14681 Gnao1 1421152_a_at,1448031_at,1460383_a 1 0.9 3 0.5 -0.1 t 22235 Ugdh 1416308_at -0.2 -0.1 0 -0.1 -0.1 14674 Gna13 1430295_at,1453470_a_at,1450656_a 0.3 0.6 1.1 1.5 2 t,1422555_s_at,1433749_at,1422556_ at,1460317_s_at 105787 Prkaa1 1437539_at -0.1 -0.3 -0.6 -0.6 -0.6 27053 Asns 1451095_at,1433966_x_at -0.2 0.1 0.3 -0.2 -0.4 18598 Pdha2 1450962_at 0.4 0.5 0.1 0.1 0.3 71743 Coasy 1423701_at,1443829_x_at -0.2 0 0.2 -0.2 0.3 12767 Cxcr4 1448710_at -0.1 -1.1 -1.1 -0.8 2.2 18436 P2rx1 1460719_a_at,1429794_a_at 0.4 0.2 0.4 1.5 0.2 21416 Tcf7l2 1425229_a_at,1429427_s_at,1429428 0.2 -1 -0.1 -1.2 -0.8 _at,1426639_a_at 16190 Il4ra 1421034_a_at,1447858_x_at,1423996 1.5 0.9 0.5 1.1 1 _a_at 18974 Pole2 1427094_at,1431440_at -0.1 -0.3 -0.9 -1.6 -1.5 56398 1500003O0 1420810_at,1450007_at,1420809_a_a 0 -0.2 0.1 0.4 0.7 3Rik t 18573 Pde1a 1431625_at,1449298_a_at 0.4 0 -0.6 0.8 -0.4 56066 Cxcl11 1419698_at,1419697_at 0.3 3.6 4.9 6.2 4.6 15486 Hsd17b2 1418352_at 2.8 3.2 0.1 0.8 3.9 17873 Gadd45b 1449773_s_at,1420197_at,1450971_a 1.1 2 2.4 2.8 2.2 t 13094 Cyp2b9 1419590_at 0.1 0.5 0.9 1.1 1 12015 Bad 1416583_at,1416582_a_at 0.1 0 -0.2 0.2 0.5 14866 Gstm5 1416842_at 0 -0.2 -0.2 -0.1 -0.4 54446 Nfat5 1439805_at,1448966_a_at,1451921_a 0.8 0.5 0.7 0.7 -0.1 _at,1438999_a_at,1439328_at,14260 29_a_at 18752 Prkcc 1421446_at,1455758_at -0.5 0.3 0 -0.2 -0.7 13433 Dnmt1 1422946_a_at,1447877_x_at,1435122 0.1 -0.4 -0.6 -0.4 1.1 _x_at 19043 Ppm1b 1425330_a_at,1451669_at,1426382_a 0.1 0.3 0.4 0.3 0.1 t 119

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 226518 Nmnat2 1436155_at 0.5 0.6 0.5 0.4 0.4 14919 Gucy2e 1422193_at 0.2 0.4 0.4 0.3 -0.2 29875 Iqgap1 1431395_a_at,1431396_at,1417379_a 0.2 -0.1 0.1 0.1 -0.1 t,1458124_at,1445724_at,1417380_at ,1434998_at 11685 Alox12e 1426039_a_at -0.4 -0.1 0.1 -0.4 -0.6 74414 Polr3c 1453256_at,1456803_at,1451658_a_a 0.6 0.9 1 1.2 0.7 t 19218 Ptger3 1450344_a_at,1425251_at 2.3 -0.8 -0.8 1.9 -0.4 21825 Thbs1 1450377_at,1460302_at,1421811_at 0 -0.1 -0.3 -0.7 0.2 14362 Fzd1 1422985_at,1437284_at 0.1 0.6 1.3 2.1 0 17884 Myh4 1458368_at,1427026_at 1.3 3.1 2.2 2.8 0.3 21991 Tpi1 1452927_x_at,1435659_a_at,1415918 0 -0.2 -0.6 -0.4 0.9 _a_at 18759 Prkci 1448695_at,1417410_s_at 0.1 -0.1 -0.2 -0.6 -0.4 14583 Gfpt1 1428715_at,1418904_at,1444329_at, 1.2 1 2.9 3.5 0.7 1449268_at,1420080_a_at,1449725_a t 17059 Klrb1c 1449570_at 0.3 0.2 0.2 0.3 -0.2 216343 Tph2 1435314_at 0.6 1.6 0.9 2 0.6 237310 Il22ra2 1437665_at 3.6 1.9 2.5 -0.2 3.7 23797 Akt3 1460307_at,1422078_at,1435879_at, 0 0.3 1.7 2.2 1.9 1435260_at 214572 Prmt7 1443011_at,1451248_at,1426096_at -0.1 -0.2 -0.9 -0.6 -1.5 18654 Pgf 1418471_at 1 1.1 2 0.6 0.4 14357 Dtx1 1425822_a_at,1458643_at 0 0.4 0.1 0.3 0.1 81905 Cacng8 1459579_at,1451864_at 1.9 1.4 1.9 0.1 -0.5 18798 Plcb4 1425339_at,1435771_at,1430871_at, 1.2 0.4 0.7 0.8 2.1 1441531_at,1425338_at 78754 Galntl2 1429236_at,1429235_at 0.3 0.5 0.2 0.1 1.2 399549 H2-M10.6 #N/A 0000 0 83456 Mov10l1 1419340_at -1.7 0.1 -2.3 0.2 0.4 12289 Cacna1d 1427974_s_at,1428051_a_at 0 0.1 0.3 1.5 2.2 18717 Pip5k1c 1450228_a_at,1424954_a_at 0 0.1 0 -0.2 0.1 329244 Il19 #N/A 0000 0 12892 Cpox 1440747_at,1422492_at,1422493_at 0.2 1.2 0.6 0.4 0.9 225471 Ticam2 #N/A 0000 0 16367 Irs1 1423104_at 0.4 -0.9 0.3 -2.3 0.2 54397 Ppt2 1418302_at 0 0.1 0.2 0.1 0.6 21990 Tph1 1419524_at 1 -0.2 -0.1 0.9 0.2 66942 Ddx18 1416070_a_at,1416071_at,1456000_a -0.1 -0.3 -0.7 -1.1 -0.8 t 53418 B4galt2 1418080_at,1448941_at 0.5 0.2 0.7 1 3 13866 Erbb2 1424919_at -0.1 1.4 -0.3 0.2 -1.2 13017 Ctbp2 1415712_at,1427200_at,1422887_a_a 0.2 0 -0.1 0 0.4 t,1434705_at,1436228_at 120

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 18018 Nfatc1 1417621_at,1428479_at,1447085_s_a 0.3 0.5 0.5 0.4 0.4 t,1447084_at,1425761_a_at 214897 Csnk1g1 1444964_at,1438246_at,1428806_at 0.1 0.1 -0.1 0.5 0 26420 Mapk9 1421878_at,1421876_at,1421877_at -0.1 -0.1 0.2 0.4 0.3 29870 Gtse1 1416969_at 0.2 0.2 -0.2 -0.5 -0.8 552899 Ugt2a2 1421484_at 0.2 -1.4 0.2 -3.6 -3.2 19013 Ppara 1439675_at,1449051_at,1457721_at 0 2 1.9 1.3 1.7 19259 Ptpn5 1425131_at,1425130_a_at,1423544_a -0.3 -0.3 1.8 0.4 0.7 t 259302 Srgap3 1425741_at,1424588_at 0 -0.1 -0.6 0.7 1.4 227377 Farp2 1424583_at,1440799_s_at 0.3 0.4 0.3 0.7 0.3 20017 Polr1b 1416126_at 0.2 -0.3 -1.1 -1.2 -1.2 13088 Cyp2b10 1425645_s_at,1422257_s_at,1451787 1.3 1.2 -0.5 -1.4 0.4 _at 71609 Tradd 1429117_at,1452622_a_at,1439910_a 0.1 -0.2 0.3 0.3 0.4 _at 329251 Ppp1r12b 1434786_at,1431462_at,1460091_at 0.3 0.6 -0.2 0 0.4 12981 Csf2 1427429_at -0.2 0.1 -0.2 -0.1 -0.7 269951 Idh2 1450048_a_at 0 -0.2 -0.3 -0.8 -1.5 14168 Fgf13 1418498_at,1418497_at 0.2 0.2 -0.1 -1.3 -1.6 13137 Daf2 1427632_x_at,1419727_at,1430457_a 0.8 -0.1 3.8 0.3 2.5 t 19395 Rasgrp2 1442264_at,1438933_x_at,1438932_a 0.4 0.2 -0.3 -0.4 -0.2 t,1417804_at 14172 Fgf18 1449545_at 0.1 2.4 0.1 1.2 -0.1 104086 Cyp27a1 1417590_at,1457665_x_at 0.2 1 1.1 1 1.9 110935 Atp6v1b1 1419373_at 0.1 2.7 1.4 0.5 0.2 11702 Amd1 1416835_s_at,1448484_at -0.1 -0.6 -1.4 -2.1 -0.6 11450 Adipoq 1422651_at -0.5 -0.6 -3.7 0.1 -0.3 19085 Prkar1b 1416754_at,1434325_x_at,1440133_x 1 1.6 2.9 1.4 0.7 _at,1440132_s_at,1416753_at 56173 Cldn14 1420345_at -0.4 1.1 -0.1 1.4 0.7 230163 Aldob 1451194_at 0 1.5 0.5 -0.2 1.2 15043 H2-T3 1452547_s_at,1452548_x_at 0.5 3.5 0.5 3.4 3.5 11636 Ak1 1423988_at,1422184_a_at -0.3 -0.1 -0.6 -0.9 -0.3 16333 Ins1 1422447_at -0.2 0.3 -0.5 -0.1 0 217325 Llgl2 1423938_at -0.2 0.1 -0.6 0 -0.1 105446 Gmpr2 1416356_at,1429180_at 0.3 -0.2 -0.4 -0.4 0.1 11839 Areg 1421134_at 1.3 1 -2 -2.8 0.6 18033 Nfkb1 1427705_a_at 0.1 0.7 0.9 0.7 -0.2 329910 Acot11 1425667_at,1429267_at -0.1 -0.2 -0.9 -1.2 -0.9 63953 Dusp10 1417163_at,1417164_at -0.5 0.2 0.1 1 0.3 12333 Capn1 1417229_at,1417228_at -0.1 0 0.2 0.2 0.2 14421 B4galnt1 1418655_at,1425363_at -0.3 -0.1 -0.4 -0.6 -0.2 17155 Man1a 1417110_at,1417111_at -0.2 0.4 0.4 0 -0.3 19125 Prodh 1417629_at 0.1 0 -2 -1.7 -0.9 121

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 232493 Gys2 1424815_at 2.9 0 0 2 2.3 16197 Il7r 1448575_at,1448576_at 0 0.1 0.7 1.3 1.7 16635 Klra4 #N/A 0000 0 117150 Pip4k2c 1416387_at,1416388_at 0.1 0.1 0 -0.1 0.7 20411 Sorbs1 1425826_a_at,1440311_at,1428471_a 4.4 5.2 1.9 4.3 4.8 t,1417358_s_at,1436737_a_at,145596 7_at 212647 Aldh4a1 1452375_at 0 0 -0.5 -0.7 -0.2 109754 Cyb5r3 1425329_a_at,1422186_s_at,1422185 0.8 0.3 0.4 0 0.9 _a_at,1430734_at 12613 Cel 1417257_at -0.2 -0.4 -0.2 0.3 -0.2 13076 Cyp1a1 1422217_a_at 0.6 0.9 1 0.7 0.4 640611 LOC640611 1422440_at,1422439_a_at -0.1 -0.4 -1.1 -1.6 -1.1

228026 Pdk1 1434974_at,1423748_at,1435836_at, 0.1 -0.1 -0.3 -0.3 0 1423747_a_at 13136 Cd55 1460242_at,1427632_x_at,1418762_a 1.7 1.3 2.3 4 2.5 t,1443906_at 19223 Ptgis 1448816_at,1445044_at 0.3 0.2 2 -0.1 2.8 67874 Rprm 1422552_at -1.5 0.9 -0.4 0.8 -0.8 22340 Vegfb 1451803_a_at -0.3 -0.1 -0.7 -2.5 -0.5 18655 Pgk1 1417864_at,1438640_x_at,1439435_x 0.1 0.1 0.1 0.1 0.4 _at 12741 Cldn5 1417839_at 1.2 2 -1.5 -0.7 1.7 230718 Nt5c1a #N/A 0000 0 242851 Gnat3 #N/A 0000 0 320207 Pik3r5 1434980_at 0.3 0.5 1 1.4 0.9 20174 Ruvbl2 1422482_at -0.2 -0.5 -1.1 -1.2 -0.7 209200 Dtx3l 1435208_at,1439825_at 0.1 2.8 3.5 3.5 3.5 387515 Tas2r144 #N/A 0000 0 75540 Fpgt 1429519_at -0.1 -0.4 0 0.2 1 26922 Mecr 1417098_s_at,1417097_at,1440553_a 0.8 0.7 0.5 -0.6 -1.5 t 21934 Tnfrsf11a 1430259_at,1419214_at 0.1 -0.1 0.3 0.3 0.2 110196 Fdps 1423418_at,1438150_at 0.3 1.4 0.3 0.1 0.5 13035 Ctsg 1419594_at 0.5 -1.3 0 0.6 0.4 268977 Ltbp1 1447547_at,1419786_at,1448870_at 0.5 2.9 2.4 3.3 4.2 16866 Lhb 1450795_at -2.1 0.1 -1.1 -0.3 -0.2 16178 Il1r2 1419532_at 0 0.3 0.1 -0.2 -0.6 218441 Zfyve16 1447947_at 0.1 0.2 0 0.1 -0.5 209558 Enpp3 1439260_a_at,1427303_at,1427302_a 0.7 0.7 1.2 0.8 -0.3 t,1452384_at,1425353_at 26987 Eif4e2 1455108_at,1421986_at,1421985_a_a 0.1 0.2 0.2 0.4 0.2 t,1435803_a_at,1435804_at 22063 Trpc1 1421096_at,1421095_a_at 0.3 0.6 0 0.3 1.1 18212 Ntrk2 1458622_at,1420837_at,1420838_at, 3.7 2.7 1.3 1.9 0.2 1437560_at,1435196_at,1435305_at, 1446712_at 122

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 15977 Ifnb1 1422305_at 3.7 3.6 7.1 7.3 1.7 320139 Ptpn7 #N/A 0000 0 66659 Acp6 1448445_at -0.1 -0.2 -1.3 -0.3 -0.2 13109 Cyp2j5 1417532_at,1417531_at 2.9 2.3 0.8 2.9 0.2 15976 Ifnar2 1440169_x_at,1427691_a_at,1451462 0.4 0.9 1.1 1.5 1.4 _a_at 26940 Ecsit 1417080_a_at -0.4 -0.8 -0.8 -1.2 -0.4 26397 Map2k3 1451714_a_at,1425456_a_at 0 -0.1 -0.2 0 0 16480 Jup 1426873_s_at -0.4 -0.2 -0.8 -1 -0.5 14194 Fh1 1424828_a_at 0 -0.2 -0.9 -2.1 -2 58200 Ppp1r1a 1422605_at -0.1 -0.2 -0.6 -1 -2.2 14858 Gsta2 1421041_s_at,1421040_a_at -0.2 0.6 1.1 1.8 4 19044 Ppox 1441862_at,1416618_at 0.1 0.2 0 0.3 0.2 71701 Pnpt1 1452677_at,1444288_at,1452676_a_a 1 1 1.8 1.6 1.1 t 12294 Cacna2d3 1419225_at 0.1 -1.8 -0.6 -2.5 0.2 13712 Elk1 1421897_at,1446390_at,1421896_at 0.4 0.4 0.2 0.3 0.8 14979 H2-Ke6 1454987_a_at -0.1 -0.2 -0.6 0 0 623474 Rad54b 1456674_at,1434734_at,1443318_at 1 0.8 1.2 0.4 0.4 140723 Cacng5 1434785_at,1426330_at -0.1 0.3 0.1 -0.2 0.2 68089 Arpc4 1423589_at,1423588_at 0 0.1 0.1 0 -0.1 21390 Tbxa2r 1419222_at -1.8 -2.8 -0.4 0.2 -0.5 107831 Bai1 1455363_at -0.1 0.4 0.3 1.9 -0.5 18012 Neurod1 1426413_at,1426412_at -0.6 -0.3 -0.3 -0.2 -0.8 54652 Cacna1f 1449955_at 0.3 -0.4 -0.7 0.1 -1.1 19055 Ppp3ca 1426401_at,1452056_s_at,1438478_a 0 0.2 0.4 0.5 0.5 _at 22276 Uros 1440535_at,1423482_at 0.2 0.1 0.8 -0.2 0.4 67710 Polr2g 1416270_at 0 0 0.1 0.5 0.7 56615 Mgst1 1415898_at,1415897_a_at 3.5 2.7 2.4 4 3.1 69836 Pla2g12b 1419614_at 2.5 1.8 1.9 1.7 2.1 243548 Prickle2 1428808_at 0.1 -1 -1.6 -4.5 -0.3 12163 Bmp8a 1449873_at 0.5 -1 0.1 0.1 -1 65964 B230120H2 1418943_at,1441897_at,1425847_a_a 0.1 -0.3 -0.1 -0.8 -1.2 3Rik t 56843 Trpm5 1443413_s_at,1449224_at,1418783_a 0.5 3.3 2.4 0.4 0.2 t 11820 App 1438373_at,1427442_a_at,1420621_a 2.2 1.4 0.4 1 0.7 _at,1438374_x_at 16621 Klkb1 1449034_at 0.9 1 2.4 2.6 1.7 58231 Stk4 1421107_at,1434159_at,1436015_s_a 0.1 0.3 0.6 0.8 0.7 t 12921 Crhr1 1427782_a_at,1418810_at 3.1 2.1 3 3.8 2.6 76722 Ckmt2 1428722_at 4.8 0 0.2 0.3 0.9 20724 Serpinb5 1441941_x_at,1424623_at,1438856_x 5.3 5.2 1.8 3.4 3.4 _at,1421752_a_at 123

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 13848 Ephb6 1418051_at -0.3 -0.2 2.3 0.1 -0.9 14799 Gria1 1435239_at,1448972_at,1458285_at 1.3 -0.1 0.1 1.4 0.8 17390 Mmp2 1416136_at,1439364_a_at 0.1 0.3 0.9 1.3 1.4 12168 Bmpr2 1419616_at,1434310_at,1441652_at 0.3 0 0.3 0.4 0 13557 E2f3 1434564_at,1427462_at 0.1 -0.3 -0.6 -0.5 -1.1 13595 Ebp 1416667_at -0.2 -0.1 -0.5 -0.5 -0.4 83964 Jam3 1423503_at,1423504_at -0.3 0.5 0.3 0.3 0.1 12568 Cdk5 1450674_at,1422590_at -0.2 -0.3 -0.3 0 0.3 12322 Camk2a 1457311_at,1442707_at,1437125_at, 1.6 0.5 1.1 0.2 3.5 1452453_a_at,1441734_at 14829 Grpr 1421470_at,1450260_at 0.1 0 0.5 -0.2 1.1 19087 Prkar2a 1432409_at,1427414_at,1428783_at, 1.8 0.3 0.3 0.1 0.2 1452915_at 77579 Myh10 1452740_at,1441057_at 1 2.5 0.3 2.4 0.3 18792 Plau 1422138_at,1422139_at 0.4 -0.4 0.2 0 0.2 56451 Suclg1 1415891_at -0.1 -0.2 -0.5 -0.8 -0.4 66885 Acadsb 1455446_x_at -0.3 -0.1 0.4 0.8 0.1 15019 H2-Q8 1430802_at 0.6 -0.5 0.2 2.4 4.1 271849 Shc4 1457118_at -0.4 -0.7 2.2 1.5 2.4 12531 Cdc25b 1421963_a_at 0 -0.7 -0.1 -1.2 0.2 216136 Ilvbl 1454658_at,1456300_at 0 -0.3 -0.2 0.1 0 668940 Myh7b 1460720_at,1422478_a_at,1457460_a 0.4 0.3 0.9 0.6 1 t,1451094_at,1444305_at,1446542_at ,1422479_at 53867 Col5a3 1425984_at,1419703_at 0.8 1 0.5 0.8 3 26424 Nr5a2 1420410_at,1449707_at,1449706_s_a 0.4 0.7 2 0.7 1.4 t 12632 Cfl2 1418067_at,1418066_at,1431432_at 0.3 -0.5 -0.1 0.1 1 15926 Idh1 1419821_s_at,1422433_s_at -0.1 0 -0.4 -0.9 -0.1 12550 Cdh1 1448261_at -0.3 -0.5 -1.9 -4.2 -4.5 235320 Zbtb16 1419874_x_at,1439163_at,1427638_a 2.6 2.7 1.5 0.9 -0.1 t 226413 Lct 1439479_at -0.2 1.1 1.1 -1 -2.7 12518 Cd79a 1418830_at 0.2 2 1.9 0.4 1.1 70101 Cyp4f16 1417277_at,1430172_a_at,1430173_x -0.1 -0.3 -0.9 -1.1 -0.8 _at 13492 Drd5 #N/A 0000 0 223753 Cerk 1434034_at 0 -0.8 -1 -0.8 0.8 69606 Mtfmt 1424908_at 0.1 -0.1 0 -0.2 0.3 18036 Nfkbib 1446718_at,1421266_s_at 0.2 0.4 0.9 1.6 1.3 12521 Cd82 1449611_at,1416401_at 0.4 2.2 0.4 2.2 0.5 18131 Notch3 1421965_s_at,1421964_at 0.6 2.9 0 0.5 3.1 21823 Th 1420546_at 0.1 0.9 2 -0.2 0.1 22122 Tsta3 1448495_at -0.1 -0.2 -0.1 0.1 0.1 21351 Taldo1 1425129_a_at -0.1 -0.1 -0.1 -0.1 -0.4 76441 Daam2 1455717_s_at,1430247_at 0.7 0.8 1 0.5 0.4 124

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 26417 Mapk3 1427060_at 0 0.1 0.1 0.2 0.9 52513 Ddx56 1423815_at 0 -0.4 -0.8 -1.8 -0.7 13079 Cyp21a1 1455691_at,1422333_at 0.4 0.5 1.3 0.1 2.4 21410 Hnf1b 1421224_a_at,1451687_a_at 0.4 0.6 2.5 2.1 1.2 64292 Ptges 1449450_at,1449449_at,1439747_at 0.6 1.3 1.3 3 3.1 18642 Pfkm 1416780_at 0.1 0.2 -0.8 -0.4 -0.2 17451 Mos 1450775_at -0.2 0.2 0 0.4 0.8 56473 Fads2 1449325_at,1443838_x_at,1419031_a 0.1 0.5 0.1 0.7 -0.5 t 12299 Cacng1 1422813_at 0 -1.9 0 0.8 0.7 23874 Farsb 1423709_s_at,1423708_a_at,1435103 0.2 0 -0.4 -2 -1 _x_at,1430986_at 235584 Dusp7 1452097_a_at,1427416_x_at,1460393 0.2 -0.4 -0.5 -0.5 0 _a_at 72082 Cyp2c55 1419582_at 0 1.2 0.8 0.7 0.3 226539 Dars2 1433838_at 0 -0.5 -0.1 0.1 0.1 15369 Hmox2 1416399_a_at -0.1 0.1 0.8 1 1.2 20562 Slit1 1425277_at 0.1 0.2 0.1 0.2 -0.4 13685 Eif4ebp1 1434976_x_at,1417562_at,1417563_a -0.2 -0.3 -0.8 -0.6 0.9 t 70560 Wars2 1429279_at,1435273_at 0 0.1 0 -0.3 -0.1 21947 Cd40lg 1422283_at -1.5 0.4 -1.1 -0.7 -1.3 16642 Klrc2 1450304_at,1421795_s_at 1 0.4 0.5 -0.5 0.6 64099 Parvg 1416875_at,1416876_at 0 0 -0.1 -0.7 0.3 14682 Gnaq 1447593_x_at,1429559_at,1428939_s 0.1 0.4 0.4 0 -0.4 _at,1428938_at,1450115_at,1428940 _at,1455729_at 78405 Ntf5 1440353_at -1.8 0.3 -1.6 0.7 -0.4 67880 Dcxr 1419456_at -0.1 -0.2 -0.4 -0.2 -0.1 106564 Ppcs 1448722_s_at,1417473_a_at -0.1 -0.5 -0.4 -0.8 0 211323 Nrg1 1456524_at 0 1.3 0.5 -3.6 -0.4 12571 Cdk6 1460291_at,1435338_at,1455287_at 0.1 0.3 -0.1 0 -1 66988 Lap3 1450860_at 0 0.3 1.1 1.7 0.4 22145 Tuba4a 1417374_at,1417373_a_at,1417375_a 0.1 2.8 0.7 1.1 -0.4 t 16994 Ltb 1419135_at 0.7 0.9 -1.3 -1.6 -2.6 17319 Mif 1454481_at,1416335_at,1433109_at 2.5 2.3 0.5 0.9 3.2 11722 Amy1 1417765_a_at 1.7 1.8 2.4 -0.4 2.2 18119 Nodal 1422057_at,1422058_at 3.7 0.3 0.3 1.9 1 20597 Smpd1 1447874_x_at,1448621_a_at -0.1 -0.1 -0.6 -0.6 0.7 12764 Cmas 1426662_at 0 -0.3 -0.8 -0.9 -0.3 58181 Il20 1421608_at -0.4 -1.1 -3.2 -0.3 -1.9 109731 Maob 1434354_at -1.5 -1.7 0 -1.5 0.2 11651 Akt1 1440950_at,1442759_at,1425711_a_a 0.2 0.3 0.1 0.4 -0.1 t,1416657_at 14387 Gaa 1419428_a_at,1436849_x_at 0 0.2 -0.2 -0.1 0.2 125

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 108037 Shmt2 1455084_x_at,1426423_at,1434204_x 0 0.4 -0.3 -0.2 -1 _at,1455985_x_at 12425 Cckar 1421195_at 2 1.7 1.8 -1.3 2 67772 Chd8 1457712_at,1443900_at,1457580_at, 2.1 0.6 3.2 0.7 3.1 1437297_at,1443711_at 26427 Creb3l1 1419295_at -0.6 -0.3 -0.8 -0.8 0.5 20888 Sult1c1 1420470_at 1 4.2 2.4 0.5 3.1 271786 Galnt13 1457045_at,1439899_at 0.5 0.3 0.5 0.6 0.5 18971 Pold1 1456055_x_at,1448187_at 0 -0.3 -0.8 -0.9 -0.5 268930 Pkmyt1 1418481_at,1438601_at 2 2.4 0 -0.2 1 59027 Nampt 1417190_at,1448607_at 0 0.4 0.6 0.6 0.2 14869 Gstp2 #N/A 0000 0 104215 Rhoq 1427918_a_at 0 -0.5 -0.7 -1 -1.1 11705 Amh 1450573_at 0.6 -0.1 -0.1 -0.8 0.2 52686 Mettl2 1445706_x_at,1444716_at,1456118_a 0.4 0.2 -0.1 -0.3 0.1 t,1435713_at 230784 Sesn2 1425139_at,1451599_at 1.4 -0.1 0.4 0.3 0.4 94045 P2rx5 1449433_at 0.4 0.4 0.4 -0.4 -0.4 71412 Dhrs2 1421663_at -0.2 -0.3 -0.3 -1.4 -1.4 22325 Vav2 1435244_at,1421272_at,1435065_x_a 0.2 0.6 0.6 -0.3 0.1 t 12162 Bmp7 1432410_a_at,1418910_at 0.4 1.3 0.5 0.3 1 22361 Vnn1 1447845_s_at,1418486_at -0.1 0.5 0.4 0.5 0.9 12671 Chrm3 1422258_at -1 0.6 -1.9 1.6 -0.1 22247 Umps 1455832_a_at,1434859_at,1431652_a 0.9 -0.3 -0.3 0.7 -0.2 t,1451445_at 18803 Plcg1 1450360_at,1442963_at,1435149_at 0 0.3 0.3 -0.1 -0.1 93685 Entpd7 1431179_at,1432068_a_at,1435625_a 2.4 0.3 3.2 0.3 1 t,1436623_at 216233 Socs2 1418507_s_at,1438470_at,1442586_a 0.6 0.8 1.3 2.3 0.9 t,1449109_at,1441476_at 12572 Cdk7 1424257_at,1458987_at,1451741_a_a 0.6 0.4 -0.2 -0.2 0.3 t,1439511_at,1435299_at 245841 Polr2h 1424473_at 0.1 -0.4 -1.2 -1.8 -0.6 53893 Nudt5 1430341_at,1448651_at 0.1 -0.1 -0.3 -0.4 -0.6 14466 Gba 1450099_a_at,1437044_a_at 0 0.1 -0.1 0.1 0.7 19263 Ptprb 1427486_at,1453908_at 0.8 2.9 1.9 4.2 3.2 11883 Arsa 1460346_at 0 -0.1 -0.3 -0.3 -0.1 93737 Pard6g 1450025_at,1420851_at 0.1 0.2 0.3 1 -0.1 21391 Tbxas1 1416827_at -0.1 -0.3 -0.5 -1 -0.8 14635 Galk1 1417177_at 0 -0.1 -0.7 -1.4 -1 20847 Stat2 1450403_at,1421911_at 0.1 3.2 4 4 4.5 20020 Polr2a 1422311_a_at,1426242_at 0.1 0.2 0.3 0.6 1.4 16974 Lrp6 1451022_at -0.1 -0.9 -1.1 -2.5 -1.2 18950 Pnp 1453299_a_at,1416530_a_at 0.2 1.4 2.2 2.6 2.3 16956 Lpl 1415904_at,1431056_a_at 0.2 0 0.2 0.3 0.3 126

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 11758 Prdx6 1423223_a_at,1442878_at 0.3 0 0 -0.1 -0.2 14425 Galnt3 1417589_at,1417588_at,1427749_at 1.3 0.1 0.3 -0.3 0.9 22627 Ywhae 1435702_s_at,1426385_x_at,1426384 0.1 0 0.1 0.2 0.4 _a_at,1438839_a_at 12062 Bdkrb2 1422263_at,1442187_at 1.7 0.3 0.6 0.6 -0.1 18821 Pln 1423359_at,1450952_at,1460332_at 0.8 0.7 0.4 1.4 0.2 193740 Hspa1a 1419625_at,1452388_at 0.2 0.1 1.7 2.4 2.3 353167 Tas2r123 #N/A 0000 0 16187 Il3 1450566_at 0.3 0.6 0.7 1.2 1.9 20773 Sptlc2 1460243_at,1454257_at,1435937_at 0.6 0.7 0.8 1.2 1.1 12477 Ctla4 1419334_at 0.6 0.4 1.9 3.5 4.7 66948 Acad8 1419262_at,1419261_at 0 -0.1 -0.2 -0.4 0.2 192654 Pla2g15 1423704_at,1422341_s_at -0.3 -1.1 -1.3 -1.1 -0.2 53857 Tuba8 1419518_at,1446771_at 3.4 1.4 2.2 2.8 3.5 13489 Drd2 1418950_at 2.3 3.7 0 2.8 1.7 18479 Pak1 1459029_at,1450070_s_at,1420979_a -0.1 0.3 0.2 0.1 1.4 t,1420980_at 24066 Spry4 1422021_at,1422020_at,1445669_at, 2.1 0.4 1 0 -0.2 1440867_at 14184 Fgfr3 1421841_at,1425796_a_at 0 1.4 0.6 0.2 -1 53897 Gal3st1 1454078_a_at 0.3 0.1 0.1 0.1 -0.5 23956 Neu2 1431936_a_at 4.4 3.9 3.5 4.5 2.7 56520 Nme4 1416798_a_at 0.1 0.1 0.1 -0.1 -1.3 387347 Tas2r118 #N/A 0000 0 69923 Agk 1431655_a_at,1424582_at,1430496_a 0.1 0.2 0.1 -0.3 0.1 t 13842 Epha8 1419341_at 0 0.4 0.1 0.3 -0.3 14634 Gli3 1456067_at,1455154_at,1450525_at 3.7 3.5 1.5 2.8 1.4 13179 Dcn 1449368_at,1441506_at 0.2 2.1 1.1 1.8 2.4 108083 Pip4k2b 1427438_at,1435068_at 0.9 1.9 3.2 0.9 1.2 72077 Gcnt3 1424901_at,1440409_at,1430963_at -0.2 0.2 0.3 2 2.4 11949 Atp5c1 1416058_s_at,1438809_at 0.2 0 -0.1 0 0 11513 Adcy7 1450065_at,1456307_s_at,1420970_a 0.2 0 0.1 0.1 0.4 t 12164 Bmp8b 1440706_at,1450342_at 0.4 0.5 0.5 0.7 0.3 100043204 Trav14n-1 #N/A 0000 0 17158 Man2a1 1448647_at -0.3 0 0.1 0.7 0.1 107272 Psat1 1451064_a_at,1454607_s_at 0 0.1 -0.1 -0.4 -1.1 16891 Lipg 1421262_at,1421261_at,1450188_s_a 0.2 0.3 0.2 0.7 -0.7 t 15985 Cd79b 1417640_at -1.6 0.3 -0.1 -1.4 0.3 103583 Fbxw11 1425461_at,1438336_at,1425462_at, 2.8 3.1 2.1 3 3.2 1447294_at,1437468_x_at 209027 Pycr1 1424556_at 0.3 0.2 0.6 0.3 0.2 127

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 111507 Igh 1451632_a_at,1451958_at,1451949_a 4.1 2.9 5 1.3 2 t,1425324_x_at,1425247_a_at,142165 3_a_at,1427758_x_at,1426197_at,142 7870_x_at,1425763_x_at,1427756_x_ at,1452577_at,1451963_at,1425385_ a_at,1429381_x_at,1452576_at,14373 46_x_at,1452538_at,1451947_at

21813 Tgfbr2 1422019_at,1425444_a_at,1426397_a -0.2 0.2 0.1 -0.4 -0.3 t 20192 Ryr3 1427427_at,1452533_at 1.6 0.7 1.2 2.3 1.6 67603 Dusp6 1415834_at -0.1 0.8 0.4 -0.2 0.5 218138 Gmds 1439428_x_at,1434158_at -0.1 0.1 0 -0.9 -2.3 19303 Pxn 1424027_at,1456135_s_at,1426085_a 0.1 -0.2 0.2 0.1 0.4 _at 26415 Mapk13 1448871_at 0.3 0.1 0.3 -0.2 -2.2 110157 Raf1 1416078_s_at,1425419_a_at 0 0 -0.2 -0.2 0 11688 Alox8 1425376_at -0.4 0.2 -0.1 0.3 -1 14345 Fut4 1455843_at,1450834_at 0.3 -0.2 0.3 -0.5 -0.7 16421 Itgb7 1418741_at -1.6 0.5 0.7 -0.1 2.1 14126 Ms4a2 1421475_at,1443264_at 4.3 1.7 0 1.2 1.5 235674 Acaa1b 1416946_a_at,1416947_s_at,1456737 1.3 0.4 0.5 1.1 0.4 _x_at,1456011_x_at,1424451_at 12273 C5ar1 1422190_at,1439902_at 0.4 1 0.9 0.9 -1.4 20890 Wnt8a 1422228_at -1.9 -1.2 0.9 0.5 0 12519 Cd80 1432826_a_at,1427717_at,1451950_a 1.7 2.5 3.3 2.8 1.5 _at,1454372_at 107766 Haao 1432492_a_at 0 0.4 0 0.2 0.1 12368 Casp6 1415995_at,1458715_at 0 -0.3 -0.5 -0.9 -0.7 319554 Idi1 1451122_at,1423804_a_at 0.3 0.5 -0.2 -0.6 -1.1 56378 Arpc3 1448279_at 0.4 0.5 0.5 1 1 16199 Il9r 1421570_at -0.2 0 0.1 0.1 0.2 14166 Fgf11 1439959_at,1421793_at 1.3 1.8 1.9 0.2 1.5 225742 St8sia5 1421735_a_at 0.5 0.7 0.8 0.4 0.3 27226 Pla2g7 1430700_a_at 0 0.1 0.2 0.4 0.7 19730 Ralgds 1460634_at 0.3 0.5 0.6 0.7 -1.5 17880 Myh11 1418122_at,1448962_at 0.2 0.4 0.3 0.4 1 20448 St6galnac4 1418074_at,1418075_at -0.1 -0.3 0.1 0.3 0.2 231329 Polr2b 1433552_a_at -0.1 0 -0.4 -0.8 -0.6 14594 Ggta1 1451843_a_at,1418483_a_at 0.1 0.5 0.4 0.2 0.7 12161 Bmp6 1450759_at -1.1 -1.1 -0.1 -2 -3.6 67634 Ftmt 1421347_at -1.1 0.5 1.2 -1.7 -0.7 17342 Mitf 1455214_at,1422025_at 0 0.7 0.7 0.8 -0.2 544791 Myh13 #N/A 0000 0 11938 Atp2a2 1437797_at,1427250_at,1427251_at, 0.4 0.1 0.1 0.1 0.1 1416551_at,1452363_a_at,1443551_a t 128

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 230979 Tnfrsf14 1452425_at 0.5 0.6 0.3 0.5 0.5 110095 Pygl 1417741_at -0.1 -0.1 -0.5 -1.4 -1.1 387356 Tas2r131 #N/A 0000 0 266632 Irak4 1451749_at,1451750_at,1421670_a_a 0.1 0 0.1 0 0 t 66945 Sdha 1433293_at,1426689_s_at,1433292_a 0 0 0.1 0 1.6 t,1426688_at 394433 Ugt1a5 1424783_a_at,1426261_s_at,1426260 -0.1 0.2 -0.1 -0.3 0.7 _a_at 18566 Pdcd1 1449835_at -0.4 0.4 0 -0.7 -0.6 100705 Acacb 1427052_at,1445754_at 0.1 0.1 0.1 0.4 0.3 215114 Hip1 1424756_at,1434557_at,1424755_at, 0.3 0 -0.3 3 -0.1 1432230_at,1432017_at 16157 Il11ra1 1459868_x_at,1417505_s_at 0 -0.1 -0.2 -0.3 0.1 19193 Pipox 1449374_at 1.3 2.2 2 2.7 -0.2 14675 Gna14 1420385_at,1449848_at,1447791_s_a 0.3 2.3 1 4.4 1.8 t 67717 Lipf 1416040_at -1.5 -0.2 0.1 1.5 -0.3 621968 Gm6273 1426772_x_at,1452205_x_at,1433108 2.6 3.3 3.8 3.2 2.7 _at 13114 Cyp3a16 1421741_at 1.1 0.9 1.3 2.4 2.9 19246 Ptpn1 1417068_a_at,1438670_at 0.1 0 -0.2 -0.3 0.1 20447 St6galnac3 1420902_at,1420903_at 2.1 0.5 1.4 0.5 -0.1 11605 Gla 1459738_x_at,1418248_at,1449006_a 5.4 1.4 0.6 3.5 3.4 t 59310 Myl10 1420805_at 1.5 1.4 2.5 2.4 0.1 21828 Thbs4 1449388_at 1.8 1.5 3.5 4.1 3.9 21803 Tgfb1 1445360_at,1420653_at 0.8 0 -0.2 -0.2 -0.3 68262 Agpat4 1428336_at,1436640_x_at 0 -0.2 -0.6 -1 0 15018 H2-Q7 1418536_at 0.6 0.5 1 2.4 3.6 73178 Wasl 1426776_at,1452193_a_at,1426777_a 0.3 0.3 0.1 0.4 -0.1 _at,1432155_at 18805 Pld1 1425739_at,1437113_s_at,1437112_a 0.2 0 -0.1 0.4 0.5 t 57813 Tk2 1426100_a_at -0.1 -0.4 -0.8 -0.2 0.5 238057 Gdf7 #N/A 0000 0 17248 Mdm4 1419558_at,1453982_at,1460542_s_a 0.6 0.4 0.4 1.3 0.4 t,1458223_at 234730 Fuk 1454634_at,1437986_x_at,1437337_x 0.5 0.7 0.1 0.8 -0.1 _at 74205 Acsl3 1452771_s_at,1428386_at,1428387_a 0.5 1.9 0.4 -0.1 2.6 t 17974 Nck2 1416796_at,1429481_at,1416797_at 1.4 0.5 2.6 3 2.8 14751 Gpi1 1434814_x_at,1450081_x_at,1420997 0 0 0 -0.4 0 _a_at 19082 Prkag1 1433533_x_at,1417690_at 0.1 -0.1 -0.7 -0.9 -0.3 13112 Cyp3a11 1416809_at -0.7 0.7 -2.3 -0.1 0.9 107895 Mgat5 1425744_a_at,1428644_at,1428643_a 1.1 0.4 0.7 -0.4 0.2 t 129

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 54411 Atp6ap1 1449622_s_at -0.1 -0.1 -0.1 -0.2 0.2 110078 Pygb 1433504_at -0.1 -0.3 -0.5 -0.4 0 207958 Alg11 1439976_at,1434187_at -0.1 -0.4 -1 -0.8 -0.6 109905 Rap1a 1424139_at,1448020_at 0 -0.1 -0.3 -0.4 -0.2 379043 Raet1e 1420603_s_at -0.5 -0.3 -1.2 -0.6 -1.3 15529 Sdc2 1431474_at,1417011_at,1417012_at, 1.6 1 0.4 1.8 1.3 1448545_at 14563 Gdf5 1419139_at 1.4 -0.4 2 -0.1 -0.3 12532 Cdc25c 1456077_x_at,1422252_a_at 4 4.5 0.5 1 2.3 116939 Pnpla3 1420655_at 0.4 0.3 0.4 0.6 0.1 110006 Gusb 1430332_a_at,1448124_at -0.1 -0.1 -0.4 -0.9 -1.2 74340 Ahcyl2 1428195_at,1419730_at,1452703_at -0.1 0 0.2 0.5 -0.1 67417 Ears2 1451471_at,1424774_s_at,1451472_a 1 -0.7 -0.9 -1.6 1.9 t 11966 Atp6v1b2 1449649_at,1415814_at,1419883_s_a 0.5 0.6 0.2 -0.1 0.3 t,1446465_at 64385 Cyp4f14 1419559_at 0.5 0.4 0.7 0.6 -0.1 12738 Cldn2 1417232_at,1417231_at 0.4 0.8 0.3 0.5 1.5 74156 Acot12 1419395_at,1449457_at,1433064_at 1.3 0.3 0.2 1 1.6 16161 Il12rb1 1418166_at 0 0.7 1.9 2.6 1.5 12534 Cdk1 1448314_at 0 -0.1 -0.5 -1.1 -1.5 73710 Tubb2b 1452679_at,1449682_s_at 0.4 -0.1 0 -0.1 1.1 58250 Chst11 1428902_at,1450509_at,1456606_a_a 0.1 -0.3 0.5 1.2 1.2 t 19703 Renbp 1450107_a_at 0.1 0 0 -0.3 -0.3 269881 Map3k10 1436373_at,1457456_at,1440500_at 1.7 1.2 0.7 1.5 2 28080 Atp5o 1416278_a_at,1437164_x_at -0.1 0 -0.1 -0.2 -0.5 66646 Rpe 1416705_at,1448444_at,1416706_at 0.2 0.1 0.2 0.6 0.3 73834 Atp6v1d 1416951_a_at,1416952_at,1438993_a 0 0.1 0.4 1.1 0.7 _at 237940 Aoc2 1449396_at -0.2 0.1 0 0.2 0 26407 Map3k4 1421450_a_at,1450253_a_at,1459800 0.2 -0.4 -0.6 -0.9 0.6 _s_at,1447667_x_at 54613 St3gal6 1454246_at,1443740_at,1449079_s_a 1.7 1.7 2.9 3 2.2 t,1447841_x_at,1449078_at 20315 Cxcl12 1448823_at,1439084_at,1417574_at 3.2 3.2 2.8 2.8 2.9 16644 Kng1 1416676_at,1426045_at 0.5 0.2 0.7 0.1 -0.3 387352 Tas2r125 #N/A 0000 0 11964 Atp6v1a 1422508_at,1450634_at 0 0 0 0.4 1.3 107508 Eprs 1430370_at,1426713_s_at,1452157_a 0.2 0.1 -0.5 -1.2 -0.1 t,1452158_at 72157 Pgm2 1437240_at,1453283_at,1451149_at 0.2 0.7 0.4 1.1 1.4 68671 Pcyt2 1420493_a_at 0.2 -0.4 -0.5 -1.3 -0.8 14104 Fasn 1423828_at -0.3 -0.7 -2.2 -3.3 -2.7 68556 Uckl1 1424646_at 0 -0.1 0.1 0.3 0.6 22178 Tyrp1 1415862_at,1415861_at,1439409_x_a 0.3 0.7 4.1 0.8 0.5 t 130

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 81535 Sgpp1 1420822_s_at,1450015_x_at,1420821 -0.1 0 0.2 -0.1 0.1 _at 12804 Cntfr 1431663_a_at,1419429_at 1.2 2.5 1.5 1.3 1.6 15482 Hspa1l 1419625_at -0.3 -0.9 1.7 1.1 0.8 70120 Yars2 1439442_x_at,1430134_a_at 0 -0.1 -1.1 -1.4 -0.4 268860 Abat 1433855_at,1422226_at 0.3 3 0.8 0.5 0.6 56513 Pard6a 1449100_at 0.1 0.1 -0.1 0.5 1 13039 Ctsl 1451310_a_at,1457724_at 0.6 0 0.4 0.2 0.7 18106 Cd244 1426120_a_at,1449991_at 0.3 -0.3 -0.5 -1.8 -0.8 11604 Agrp 1421690_s_at -0.9 0.6 -3.4 -1 -0.7 23918 Impdh2 1415851_a_at,1415852_at 0.2 -0.1 -0.6 -1.7 -2 432676 Gm5436 1437164_x_at -0.2 -0.2 -0.4 -0.6 -1 78914 Nadsyn1 1430359_a_at 0 -0.3 -0.6 -0.6 0 245847 Amdhd2 1434855_at -0.1 -0.4 -0.4 -0.2 0.9 22146 Tuba1c 1448232_x_at,1433584_at,1416128_a 0.1 -0.1 -0.4 0 0.5 t 102626 Mapkapk3 1434815_a_at,1437494_at 0 -0.4 -0.6 -0.8 -0.5 18711 Pikfyve 1452994_at,1422994_at,1446974_at 0.3 0.2 0.3 0.1 0.3 19727 Rfxank 1455371_at,1425670_at,1419310_s_a 0.5 0.1 0.3 0.3 1.4 t 18099 Nlk 1456467_s_at,1435970_at,1419112_a 0 -0.3 -0.8 -0.8 -0.4 t 216558 Ugp2 1426461_at,1434485_a_at,1434486_x -0.1 0 -0.2 0 0.7 _at,1451742_a_at,1426460_a_at 12833 Col6a1 1448590_at 0.6 1.3 1.4 -1.5 -1.7 387353 Tas2r126 #N/A 0000 0 74754 Dhcr24 1418130_at,1451895_a_at,1418129_a -0.1 0 -0.7 -1.2 -0.7 t 16330 Inpp5b 1451330_a_at -0.1 -0.1 0.6 1.4 1.1 14584 Gfpt2 1418753_at -0.7 -0.7 -0.2 0.4 -1.3 223881 Rnd1 1455197_at 1.1 2 0.3 0.1 0.4 16452 Jak2 1421066_at,1421065_at 0.1 0.4 0.9 0.9 -0.1 14715 Gnrhr 1421665_a_at,1427731_at,1427694_a 0.5 0.5 0.3 0.5 0.2 t 14677 Gnai1 1427510_at,1454959_s_at,1434440_a 0.9 1.6 1.1 1.2 0.2 t 68961 Phkg2 1428511_at 0 -0.1 -0.3 -0.2 -0.1 15378 Hnf4a 1450447_at,1427001_s_at,1427000_a 0.2 4.7 0.2 1.1 5.6 t,1421983_s_at 56508 Rapgef4 1425518_at,1421622_a_at 3.3 3.7 3.6 2.5 0.7 223774 Alg12 1424818_at,1427558_s_at,1427557_a -0.1 -0.2 -0.4 -0.4 0.1 t 19052 Ppp2ca 1456390_at,1417367_at 0 0 0 0.2 0.1 18045 Nfyb 1419266_at,1419267_at 0.1 -0.1 -0.1 -0.2 -0.2 67680 Sdhb 1418005_at 0 -0.1 -0.1 0.1 0.4 14121 Fbp1 1448470_at 0.2 0.5 0.2 1.1 0.3 22412 Wnt9b 1451711_at,1443197_at 0.8 1.5 0.9 1.7 1.9 131

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 12496 Entpd2 1418259_a_at 0.1 0.2 0.2 -0.4 -0.1 12524 Cd86 1449858_at,1420404_at 0.1 0.7 2.1 3.3 3.5 13543 Dvl2 1448616_at,1417207_at 0.2 -0.1 -0.2 -0.7 -0.8 16415 Itgb2l 1433053_at,1449829_at,1433054_at 0.8 0.4 0.4 0.9 0.6 18534 Pck1 1423439_at,1439617_s_at,1455209_a 2.8 2.9 -0.1 0.6 3.1 t 20454 St3gal5 1449198_a_at,1460241_a_at 0.1 0.1 0.3 0.7 -1.1 18088 Nkx2-2 1421112_at 0.7 1.4 1 4.1 0.6 18648 Pgam1 1426554_a_at -0.1 -0.2 -0.3 0 0.5 21923 Tnc 1456344_at,1416342_at -0.1 -0.2 -0.9 -2.1 -1 100039790 Gm2426 #N/A 0000 0 12660 Chka 1453582_at,1442277_at,1450264_a_a 0.3 -0.1 -0.4 -0.3 -0.3 t 19668 Rbpjl 1450433_at,1421956_at 0.1 0.5 0.3 0.3 0.3 106759 Ticam1 1454676_s_at -0.1 -0.3 -0.3 0.5 1.8 76551 Ccdc6 1428311_at,1459159_a_at 0 0.5 0.6 0.3 0.6 18128 Notch1 1418634_at,1418633_at 0.2 0.5 0.6 0.5 1.6 67758 Aadac 1448813_at 0.3 -0.2 -1 -2 -2.2 93735 Wnt16 1422941_at 0 -1.7 -1.9 -0.4 -0.8 110696 H2-M10.3 #N/A 0000 0 192166 Sardh 1448426_at,1416662_at 0.1 0.2 0.9 0.6 -0.3 13096 Cyp2c37 1419094_at 0 1 0.4 -1.5 1.3 320202 Lefty2 1436227_at 0.5 3.4 0.5 4.4 1.4 229487 Pet112l 1444502_at,1424282_at 1.4 1.2 1 1.3 0.4 27056 Irf5 1460231_at -0.1 -0.2 0.2 0.2 0 99035 Olah 1451510_s_at,1424855_at 0.5 0.9 0.3 0.6 0.8 20832 Ssr4 1427096_s_at,1435709_at,1448524_s 0 -0.1 -0.1 -0.4 -0.3 _at 14381 G6pdx 1422327_s_at,1448354_at 0 0 0.1 0.3 0.8 110460 Acat2 1425195_a_at,1435630_s_at 0.1 0 -0.3 -1.2 -0.8 110960 Tars 1460323_at 0 -0.3 -0.5 -1.2 -0.7 69976 Galk2 1455798_at 0 -0.2 -0.1 -0.3 0 18585 Pde9a 1449403_at 0.3 0.3 1.1 0.3 0.7 669888 LOC669888 #N/A 0000 0

20022 Polr2j 1440065_at,1417720_at 0.5 0.3 0.2 0.2 0.6 394436 Ugt1a1 1424783_a_at,1426260_a_at,1426261 -0.1 0.2 -0.1 -0.3 0.7 _s_at 16419 Itgb5 1456133_x_at,1417534_at,1456195_x -0.1 -0.1 -0.6 -0.9 0.9 _at,1417533_a_at 13113 Cyp3a13 1419523_at 0.7 1.1 1.3 -1.8 0.8 404549 Ifna14 1422404_x_at,1422403_at 0.5 1.2 1.5 2.4 1.3 66514 Asrgl1 1424396_a_at,1424395_at,1460360_a 0.8 1.1 0.5 -0.7 1.7 t 66812 Ppcdc 1424336_at,1424335_at,1430813_at 1.1 0.5 0.1 1.4 0.6 132

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 69632 Arhgef12 1446965_at,1423902_s_at,1451159_a 0.5 0.1 -0.3 -0.3 0 t,1453853_a_at 18015 Nf1 1438067_at,1441523_at,1452525_a_a 0.5 0 0.1 -0.2 -0.2 t 71742 Ulk3 1431112_at 0.2 0.3 0.6 -1.9 0.2 20887 Sult1a1 1427345_a_at 0.1 -0.6 -1.7 -0.7 0 19206 Ptch1 1439663_at,1428853_at,1450824_at 1 1 0.8 1.3 -0.2 26401 Map3k1 1443540_at,1424850_at 0 -0.4 -0.5 0.1 0.2 14913 Guca1a 1421061_at 0 0.1 0.1 0 -0.1 16434 Itpa 1416448_at,1442353_at 0.1 -0.4 0 -0.3 0.3 83702 Akr1c6 1417085_at 0.4 0.1 0.1 0.5 0.7 69745 Pold4 1427885_at -0.1 -0.2 -0.7 -0.8 -0.1 26938 St6galnac5 1419420_at,1449468_at -0.1 0.5 0.5 0.5 1.4 16993 Lta4h 1434790_a_at,1453528_at,1426807_a 0.1 -0.3 -0.7 0.2 0.1 t 12325 Camk2g 1423942_a_at,1423941_at 0.2 -0.4 -0.6 -0.8 0.5 18102 Nme1 1435277_x_at,1424110_a_at -0.1 -0.2 -0.4 -1.3 -1.7 107476 Acaca 1434185_at,1427595_at 0.1 0 -0.1 -0.5 -0.7 77116 Mtmr2 1425460_at,1425459_at -0.1 0 -0.1 0.2 -0.4 230145 Galnt12 1437760_at 0.2 -0.5 -0.2 0.4 0.1 14103 Fasl 1449235_at,1418803_a_at 2 1.7 2.5 1.7 0.9 394435 Ugt1a6b 1426261_s_at,1426260_a_at,1424783 -0.1 0.2 -0.1 -0.3 0.7 _a_at 667772 Myh15 #N/A 0000 0 13642 Efnb2 1419639_at,1449549_at,1449548_at, 0.3 0.6 0.2 0.6 -0.4 1419638_at 380959 Alg10b 1454917_at,1437879_at -0.2 -0.1 -0.3 -0.3 -0.3 11474 Actn3 1418677_at -3 -2.3 -2.8 0.3 -0.3 68775 Atp6v1c2 1430306_a_at 1.2 0.4 0 0.4 -0.2 20927 Abcc8 1455765_a_at,1457066_at 0 0.1 -0.1 0.8 0.1 24055 Sh3bp2 1448328_at 0.1 0.4 0.7 0.9 1.1 20354 Sema4d 1420823_at,1420824_at 0 0.2 0.9 0.9 0.5 320438 Alg6 1439007_at -0.1 -0.2 -0.7 -1 -1.3 99167 Ssx2ip 1449764_x_at,1420185_at,1417514_a 0 0.1 0.8 0.3 1.6 t,1448743_at 242700 Il28ra 1460598_at -0.7 -0.6 -1.9 -1.6 -1.7 20700 Serpina1a 1420553_x_at,1449321_x_at,1451513 0.4 3.3 0.7 0.4 0.9 _x_at 117600 Srgap1 1431719_a_at -0.4 0.3 0.4 0.6 0.8 21937 Tnfrsf1a 1417291_at 0 0.4 0.8 0.7 0.7 20444 St3gal2 1421890_at,1421891_at,1421892_at 0.2 0 -0.3 -0.4 -0.2 18628 Per3 1421087_at,1460662_at,1441445_at, 2.7 1.3 1.7 1.9 1.2 1458176_at,1442243_at,1421086_at

21926 Tnf 1419607_at 1.8 0.7 1.5 1.1 -2.1 11409 Acads 1460216_at 0 -0.2 -0.3 -0.4 -0.4 24088 Tlr2 1419132_at 0.3 0.3 0.4 0.6 -1.2 133

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 56292 Naa10 1417118_a_at -0.2 -0.3 -0.7 -1.9 -1.4 109093 Rars2 1424209_at 0 -0.5 -0.5 -1.3 -0.9 74776 Ppa2 1424488_a_at -0.1 0 -0.3 -0.9 -0.6 17749 Polr2k 1452596_at 0.1 -0.2 -0.2 -0.4 -0.3 19059 Ppp3r2 1437535_at 0 0.7 0.5 0.5 0.1 212996 Wbscr17 #N/A 0000 0 269378 Ahcy 1417125_at -0.1 0 -0.4 -1.1 -2.2 12265 Ciita 1421211_a_at,1421210_at 0.2 0.5 1.2 1.3 -0.1 67938 Myl12b 1428608_at,1428609_at 0.2 0 0.3 0.1 0.3 380928 Lmo7 1455056_at,1458453_at 0.4 1.7 1.3 0.6 0.5 218865 Chdh 1455435_s_at -0.6 -1.4 -0.6 0.9 1 14714 Gnrh1 #N/A 0000 0 18132 Notch4 1449146_at,1456263_at,1436901_at 1.1 0.7 2.2 1 2 69920 Polr2i 1428494_a_at -0.1 -0.4 -0.7 -0.6 0.1 17436 Me1 1416632_at,1430307_a_at 0 0.2 0 -0.2 0.3 11957 Atp5j 1416143_at 0 -0.1 -0.1 -0.3 -0.3 17962 Nat3 1422961_at 0.2 0.9 2.6 1.6 0.3 230396 Ifna13 1422403_at,1450593_at,1422404_x_a 0.5 1.2 4.5 3.5 1.3 t 78600 Pde6h 1450765_a_at,1450766_at 0.2 1.2 0 0.1 0.2 107885 Mthfs 1460257_a_at,1443021_at 0.7 0.6 0.4 1 0.7 53618 Fut8 1460319_at,1443656_at,1456367_at -0.1 0.2 1.1 1.5 1.1 70750 Kdsr 1435899_at,1440331_at,1428559_at 0.1 0.3 0 -0.5 -1.3 15112 Hao1 1420420_at 0.6 1.1 0.5 1 -1.3 18755 Prkch 1422079_at,1434248_at 0 -0.6 -1 -0.7 -0.9 11491 Adam17 1421857_at,1421859_at,1421858_at 0 0.1 0.3 0.3 -0.6 12846 Comt1 1449183_at,1418701_at -0.1 -0.6 -0.8 -1.5 0 69983 Sis #N/A 0000 0 333715 H2-M10.2 #N/A 0000 0 23887 Ggt5 1439420_x_at,1455747_at,1418216_a 0.5 0.7 0.5 0.5 1.9 t 66335 Atp6v1c1 1419546_at,1419545_a_at,1419544_a -0.1 -0.2 -0.2 -0.2 0.2 t 69241 Polr2d 1424258_at 0.1 -0.2 -0.6 -0.8 -0.6 269614 Pank4 1435004_at 0.3 -0.5 -0.5 -0.5 -0.3 12913 Creb3 1424742_at,1424741_s_at,1424740_a 0 0.6 0.4 0.4 0.6 t,1419979_s_at 11480 Acvr2a 1451004_at,1437382_at 0.2 -0.6 -0.5 -0.3 -0.7 12364 Casp12 1418981_at,1449297_at 1.6 0.7 3.3 3.3 1.5 108100 Baiap2 1451027_at,1435128_at,1451028_at, 0.2 0.3 0.8 0.5 1.8 1425656_a_at 18019 Nfatc2 1426032_at,1425990_a_at,1425901_a 0.9 1 1.3 0.4 1 t,1439205_at,1440426_at,1426031_a _at 11973 Atp6v1e1 1457049_at,1449712_s_at,1449711_a 0.6 1.2 0.3 0.5 0.8 t,1420038_at 134

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 77805 Esco1 1424324_at,1424325_at 0 -0.2 -0.2 -0.2 0 14251 Flot1 1448559_at 0 -0.1 -0.7 -0.5 -0.2 671652 Gm16452 #N/A 0000 0 54673 Sh3glb1 1418011_a_at,1418012_at,1418010_a 0.1 0.1 0.5 0.9 1.4 _at 226143 Cyp2c44 1424576_s_at -2.5 -2.5 -1.5 -2.3 -2.9 58998 Pvrl3 1417319_at,1421133_at,1421132_at, 4.2 2.3 4.5 2.1 3 1423331_a_at,1448673_at 13480 Dpm1 1449438_at,1419353_at 0.2 1 -0.3 0.6 0.3 26409 Map3k7 1449693_at,1455441_at,1447801_x_a 0.4 0.1 -0.1 -0.7 -0.4 t,1419988_at,1425795_a_at,1426627 _at 80914 Uck2 1417137_at,1439741_x_at,1448604_a 0.8 1.8 -0.2 0 0.6 t,1439740_s_at,1457980_x_at,142690 9_at 224105 Pak2 1454887_at,1434250_at -0.1 0.1 -0.1 -0.5 -0.8 18115 Nnt 1416105_at,1456573_x_at,1432608_a -0.1 0.7 0.5 0.6 0.3 t 93747 Echs1 1452341_at -0.2 -0.4 -0.8 -1.3 -0.1 330260 Pon2 1425791_at,1429020_at,1450686_at, 0.8 0.5 0.3 0.3 0.6 1429019_s_at 11512 Adcy6 1418128_at 0.8 0.7 1.7 2.2 1.6 66313 Smurf2 1429045_at,1429046_at -0.1 -0.1 0 0 -0.3 15211 Hexa 1449024_a_at 0 -0.1 0 -0.1 0.1 11717 Ampd3 1422573_at 0 0.2 -0.4 -0.3 -0.8 75826 Senp2 1455327_at,1425465_a_at,1451717_s 0 0 0.1 -0.2 0 _at,1425466_at 13835 Epha1 1432400_at,1422917_at,1432399_a_a 0.8 1.5 2.7 3.3 3.7 t 22422 Wnt7b 1420891_at,1420892_at 0.8 0.8 -0.7 -1.8 -0.3 22062 Trp73 1427697_a_at,1452325_at 0.1 0.6 0 -1.2 -0.8 20810 Srm 1421260_a_at -0.3 -0.7 -2.2 -3.8 -3.2 12223 Btc 1435541_at,1421161_at 0.7 0.4 0.9 0.5 0.7 15483 Hsd11b1 1449038_at 0.2 -0.1 0 -0.6 -0.7 114875 Plcz1 1432405_a_at,1422658_at -0.1 -0.1 0.7 0.7 0.4 19876 Robo1 1427231_at,1457407_at 3.4 0.2 0 2.4 4.4 268782 Agxt2 1435838_at 1.9 2 2.7 0.6 3.2 14170 Fgf15 1418376_at 1.1 0.2 -0.1 2.1 -0.2 15975 Ifnar1 1442222_at,1449026_at 0.4 0.3 0.7 0.8 0.1 72349 Dusp3 1434472_at,1456769_at,1425608_at 0 -0.1 -0.1 0.2 0.3 621628 Cldn20 #N/A 0000 0 74145 F13a1 1448929_at -0.1 0.1 -0.1 -0.6 -1.9 74055 Plce1 1452398_at 1.1 0.5 1.7 -0.3 0.7 11720 Mat1a 1423147_at -1.6 0.2 0.9 0.6 -1.2 15929 Idh3g 1416788_a_at,1416789_at 0 -0.1 -0.2 -0.7 -0.8 12902 Cr2 1425289_a_at -0.2 -1.7 -3.1 -1.6 -2.6 330662 Dock1 1452220_at,1443991_at -0.2 0.1 -0.1 -0.3 -1.2 135

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 11549 Adra1a 1421659_at,1459351_at -2 -0.4 0.3 -1.6 -1.9 229927 Clca4 1451823_at 2.1 2.2 0.8 0.3 0 13118 Cyp4a12b #N/A 0000 0 107650 Pi4kb 1439197_at,1441549_at 0.1 0.2 0.3 0.2 -0.2 94215 Ugt2a1 1421484_at 0.2 -1.4 0.2 -3.6 -3.2 14626 Gk2 1416694_at 0.9 0.3 0.6 2.1 -0.5 14102 Fas 1460251_at 0.1 1.1 1.2 0.8 -0.3 112408 Tas2r116 #N/A 0000 0 16391 Irf9 1421322_a_at 0.1 1.7 1.8 1.7 1.9 66190 Acer3 1438435_at,1429520_a_at,1459771_x 0 0.6 1.2 0.8 -0.3 _at,1453179_at 387343 Tas2r109 #N/A 0000 0 12313 Calm1 1423807_a_at,1455571_x_at,1454611 0.2 0.2 0.2 0.7 0.8 _a_at,1422414_a_at,1450864_at,143 3592_at,1417365_a_at,1417366_s_at

13166 Dbh 1459848_x_at,1447592_at,1450670_a 2.1 3.2 2 1.9 1.2 t 81600 Chia 1416456_a_at 0.2 0.3 -0.1 -0.1 -0.1 17308 Mgat1 1423609_a_at 0 0.4 0.6 0.7 0.6 27060 Tcirg1 1420635_a_at 0.2 0.1 0.7 1 0.9 11484 Aspa 1418472_at 0 0.6 0.2 -0.2 -0.9 208449 Sgms1 1436499_at,1426576_at,1426575_at, 0.1 -0.4 -0.5 -0.6 -1.2 1442079_at 80903 Fgf16 1420806_at 0.8 -0.3 0.2 0.2 -0.6 11798 Xiap 1426636_a_at,1450231_a_at,1456088 1.1 1.4 1.8 1.3 0.3 _at,1421394_a_at,1450232_at,14375 33_at,1453385_at 14061 F2 1418897_at 2.3 2.6 2.5 2.8 1.7 12394 Runx1 1440878_at,1427847_at,1427650_a_a 0.6 1.1 1.1 1.3 1.4 t,1452578_at,1422865_at,1452530_a _at,1422864_at,1452531_at 13001 Csnk2b 1416728_at 0 0 0.3 0.3 0.4 234724 Tat 1451557_at 0.3 3.3 0.2 3.6 0.6 71911 Bdh1 1426959_at,1452257_at 0.3 -0.2 -0.5 -1.5 -0.8 329504 Lcmt2 1433518_at -0.3 -0.3 -0.6 -1.3 -0.7 50773 Nt5c 1417252_at 0 0 0 -0.4 -0.6 11783 Apaf1 1452870_at,1450223_at 0.1 0.5 1.2 0.9 -0.1 16414 Itgb2 1450678_at 0 0 0.1 0.2 0.3 21881 Tkt 1436605_at,1439443_x_at,1451015_a 0.1 0 -0.1 -0.5 -0.7 t 16973 Lrp5 1449299_at 0 0.1 0.3 0.3 -0.1 18799 Plcd1 1416675_s_at,1448432_at -0.2 -0.3 -0.1 -0.7 -0.9 12562 Cdh5 1422047_at,1433956_at 0.3 1.1 0.7 0.4 1.1 136

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 14433 Gapdh AFFX-GapdhMur/M32599_M_at,AFFX-0.1 0.2 0.2 0.2 0.4 GapdhMur/M32599_5_at,1418625_s_ at,AFFX- GapdhMur/M32599_3_at,1447999_x_ at,1457612_at

15563 Htr5a 1443276_at,1422207_at 0.8 0.2 -0.4 2.6 2.2 14127 Fcer1g 1418340_at 0.1 0.1 0.1 0.4 0.4 246256 Fcgr4 1425225_at 0.7 1.8 3.2 4.6 4.7 17768 Mthfd2 1419253_at,1419254_at 0 0.7 1.1 1 0.6 14256 Flt3l 1422115_a_at -0.1 0.2 -0.1 0.4 0.5 11846 Arg1 1419549_at -0.2 -0.7 -1.6 -2.9 0.5 14257 Flt4 1421442_at -0.2 -0.2 0.2 1 0.8 94213 Ddx50 1439082_at,1453852_at,1417875_at 0.3 0 -0.2 -0.2 -0.3 227619 Man1b1 1452235_at 0 -0.1 -0.6 -0.4 0.3 60504 Il21r 1450456_at 0.3 1.1 1.8 1.4 1.8 434428 Gm5620 1416128_at,1433584_at,1448232_x_a 0.1 -0.1 -0.4 0 0.5 t 56043 Akr1e1 1417826_at,1446483_at 0.1 -0.2 0.3 -0.1 0.6 11364 Acadm 1415984_at -0.1 -0.3 -0.7 -0.9 -0.6 208624 Alg3 1460742_at 0.1 0 -0.4 -0.7 -0.6 12579 Cdkn2b 1449152_at -0.1 0.1 -0.3 -0.2 -0.8 12928 Crk 1436835_at,1425855_a_at,1416201_a 0.9 0.7 0.8 0.6 0.4 t,1448248_at,1460176_at 73699 Ppp2r1b 1419871_at,1428265_at -0.1 -0.1 -0.2 -0.4 -0.9 100198 H6pd 1452145_at -0.1 -0.1 0 -0.3 1 93762 Smarca5 1424205_at,1424207_at,1440048_at, 0.4 0.1 0 -0.5 -0.6 1424206_at 20807 Srf 1418255_s_at,1418256_at 0.3 0.1 -0.4 -0.4 0 56727 Miox 1416460_at 3.1 0.2 2 0 -0.1 12040 Bckdhb 1427153_at 0.1 -0.5 0.6 1 0 53791 Tlr5 1450242_at 0.2 0.9 0.8 -0.4 -0.6 14719 Got2 1447768_at,1430397_at,1417715_a_a 0.9 1.5 1.1 0.7 0.3 t,1417716_at 54611 Pde3a 1450284_at,1431914_at,1431913_a_a 3.2 2.8 2.5 3.8 2.6 t 16165 Il13ra2 1422177_at -0.3 -0.8 -0.7 0.5 -2.6 67877 Naa20 1418244_at 0 0 0.2 0.2 0.4 56720 Tdo2 1419093_at,1449337_at 0.3 0 -0.7 0.3 0 12575 Cdkn1a 1421679_a_at,1424638_at 0.6 2 2.3 2.3 1.4 170716 Cyp4f13 1418767_at 0 -0.1 -0.1 0.3 0.7 16449 Jag1 1421105_at,1434070_at,1421106_at 0.4 0.3 0.5 0.3 -0.2 13618 Ednrb 1423594_a_at,1437347_at,1426314_a 0 0.5 -0.1 0 -0.1 t 50723 Icosl 1419212_at,1426087_at 0.6 0.2 0.3 0.6 0.1 16001 Igf1r 1452108_at,1452982_at,1428967_at, 0.3 0.2 -0.3 -0.3 -0.3 1446303_at,1426565_at 137

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 245616 Kir3dl1 #N/A 0000 0 110119 Mpi 1451540_at 0.1 0.1 0.3 0.2 0.6 17086 Ncr1 1422089_at -0.7 0.4 -0.7 -1.5 -0.4 75512 Gpx6 1452135_at 0.1 0.3 -1 -0.6 -0.1 19353 Rac1 1437674_at,1451086_s_at,1423734_a 4.9 2.6 3.4 1 2.8 t 93687 Csnk1a1 1430529_at,1424827_a_at,1451497_a 0.5 0.1 0.3 0.5 0.1 t,1428537_at 217664 Mgat2 1452037_at,1426350_at -0.2 -0.2 -0.6 -0.7 0 22416 Wnt3a 1422093_at -1.2 0 0.3 -0.3 -0.9 104458 Rars 1416312_at 0.1 -0.1 0.4 0.6 0 234779 Plcg2 1426926_at -0.1 0.1 0 -0.2 -0.8 14537 Gcnt1 1460431_at,1449538_a_at 0.2 -0.4 -0.2 -0.8 0.1 18719 Pip5k1b 1421833_at,1421834_at,1450389_s_a 1.6 1.5 1.2 0.8 0.8 t 56613 Rps6ka4 1448498_at,1438243_at 1 0.5 0.9 0.3 0.4 18705 Pik3c2g 1421704_a_at 3.9 1.6 1.1 0.9 3.1 59035 Carm1 1419743_s_at 0 -0.1 0 -0.5 -0.3 208647 Creb3l2 1437396_at,1452381_at 0.3 -0.2 -0.2 -1.5 -0.4 320685 Dctd 1454659_at 0.1 -0.3 0 0 -1.4 15160 Serpind1 1418680_at 1.3 0.7 -0.3 1.3 1.4 19042 Ppm1a 1417221_at,1451943_a_at,1425537_a 0.7 0.6 0.1 0.3 0.9 t,1429501_s_at,1443903_at,1453171_ s_at,1429500_at,1415678_at 14255 Flt3 1419538_at -0.6 -0.3 0.3 -0.7 1.1 11428 Aco1 1447080_at,1456728_x_at,1423644_a 0.2 0.5 0.1 -0.5 0.2 t 16402 Itga5 1457561_at,1423268_at,1458996_at, 0.7 0.2 0.7 1.5 2.2 1423267_s_at 58994 Smpd3 1450748_at,1438665_at,1422779_at 1.8 1.3 1.4 2.2 1.7 627557 Gm6768 1420808_at,1450006_at -0.1 0.2 0.5 1.2 1 19054 Ppp2r3d 1455198_a_at 0.4 0 -0.1 0.3 -0.3 54635 Pdgfc 1449351_s_at,1419123_a_at 0.2 -0.1 1.2 1 1.3 22143 Tuba1b 1448232_x_at,1423846_x_at,1416128 0.1 -0.1 -0.3 -0.2 0.5 _at 17698 Msn 1450379_at,1421814_at 0 0.1 0.2 0.5 0.1 13195 Ddc 1430591_at,1426215_at 0.1 0.7 0 0.3 0 270076 Gcdh 1448717_at -0.2 -0.4 -0.6 -1.5 -0.4 15969 Ifna6 1422404_x_at,1450593_at,1422403_a 0.5 1.2 4.5 3.5 1.3 t 15507 Hspb1 1422943_a_at,1425964_x_at 0.3 0.3 0.2 0.1 0.1 20191 Ryr2 1450123_at,1421126_at 1.8 2.1 0.4 2.7 1.1 13075 Cyp19a1 1449920_at 0.4 0.2 0.2 -0.1 -2 16514 Kcnj11 1455417_at,1450515_at 0.4 0.5 0.2 0 0.2 14872 Gstt2 1417883_at 0.1 0 -0.3 0.2 0.1 101502 Hsd3b7 1416968_a_at 0.1 -0.4 -0.4 -0.3 0.9 21337 Tacr2 1422234_at 0.6 1.7 0.1 1.2 1.2 138

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 114143 Atp6v0b 1425448_x_at,1437013_x_at,1416769 0.1 0 0.1 0.2 0.2 _s_at 22035 Tnfsf10 1420412_at,1439680_at,1459913_at -0.1 3.7 5.2 6.7 5.5 15212 Hexb 1437874_s_at,1460180_at 0 0 -0.2 0 0 13845 Ephb3 1451550_at 0.6 0.6 -0.8 0.7 0.7 319478 Cxxc4 1456811_at,1437351_at,1438304_at 0.4 0.8 0.6 2.5 0.9 18176 Nras 1422687_at,1454060_a_at,1422688_a 0.1 0.1 0.2 0.1 0.1 _at 11607 Agtr1a 1436739_at 2.6 5.1 0.9 2.9 2.7 20583 Snai2 1418673_at,1447643_x_at 1.3 0.6 -0.1 1.5 3.3 23984 Pde10a 1419389_at,1419390_at,1439618_at, 2.2 3.5 1.2 5.1 4.1 1458499_at,1432490_a_at 11363 Acadl 1448988_at,1448987_at 1.4 0.5 0.5 1 0.9 19268 Ptprf 1420842_at,1420841_at,1420843_at 1.3 1.1 1.5 2.4 4.5 18575 Pde1c 1444386_at,1426036_a_at,1429643_a 3.8 0.7 0.7 0.4 1.7 _at,1444067_at,1436251_at 52858 Cdipt 1436715_s_at,1423657_at 0 0 -0.1 0 0.3 76709 Arpc2 1437148_at,1442295_at 0.4 0 0.1 0.2 0.3 387351 Tas2r124 #N/A 0000 0 110208 Pgd 1423706_a_at,1437380_x_at,1436771 0.1 0.1 0.2 0.2 0.2 _x_at,1438627_x_at 18844 Plxna1 1428623_at,1421232_at -0.1 -0.5 0 0.1 0.2 66454 Nmnat1 1429819_at,1425773_s_at 0.3 0 0.4 0.8 0.9 73724 Mcee 1438477_a_at -0.1 -0.3 -0.5 -1.2 -0.7 20021 Polr2c 1416341_at 0.2 0.1 0.2 0.1 0.1 71797 Chst13 1453462_at -0.4 0.7 0.1 -2.2 -2.8 99470 Magi3 1421035_a_at,1450101_a_at,1435461 0.3 0.2 0.7 0.2 -1 _at 104110 Adcy4 1418098_at 0.3 0.5 0.2 0.4 -0.2 64051 Sv2a 1423406_at 1.1 0.5 0.4 0.6 -0.6 11671 Aldh3a2 1415776_at -0.1 -0.1 0 -0.4 -0.1 78394 Ddx52 1434607_at,1434608_at 0 -0.1 -0.3 -0.2 0.2 109821 F11 1451788_at -2.7 0 -2.4 -3.9 -0.7 12495 Entpd1 1453586_at,1450939_at,1423326_at 0 0.1 0.9 1.3 1.4 26400 Map2k7 1425512_at,1440442_at,1457182_at, 0.5 0.1 1.3 -0.2 0.5 1421416_at,1425513_at,1451736_a_a t,1425393_a_at 75747 Sesn3 1449303_at,1453313_at 0 0.1 1.4 2 2.1 20028 Pdc 1449179_at -0.1 1.6 0.4 1 -0.5 75735 Pank1 1431028_a_at,1418715_at,1429813_a 0.2 1.4 0.2 0.5 0.4 t,1429814_at,1457110_at 16439 Itpr2 1427693_at,1427287_s_at,1421678_a 0.3 0.4 0.3 0.7 1.9 t,1424834_s_at,1444418_at,1424833_ at 13176 Dcc 1440487_at,1422162_at,1441572_at 1.1 3.1 2.6 0.9 0.3 18194 Nsdhl 1458831_at,1416222_at 0.5 0.1 -0.4 0.3 -0.7 75986 Agmat 1427214_at 0 0.2 0.7 -0.9 0.9 139

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 53624 Cldn7 1448393_at -2.1 0.9 -0.2 0.6 -2.9 16971 Lrp1 1448655_at,1442849_at 0.4 -0.5 -0.5 -0.2 -0.2 11950 Atp5f1 1426742_at,1433562_s_at 0 0 -0.2 -0.3 -0.2 16772 Lama1 1418153_at 0.3 0.7 1.3 1 2.5 22262 Uox 1422604_at 0.7 1.2 1.4 1 0.7 11647 Alpl 1423611_at 0 -0.1 -0.1 0.1 -0.2 104112 Acly 1439445_x_at,1425326_at,1446315_a 0 0 0.2 0.1 0.6 t,1439459_x_at,1451666_at,1438389_ x_at 217480 Dgkb 1455361_at,1442860_at,1440901_at 1.8 1.8 2.1 2.1 1 28169 Agpat3 1433818_at,1450504_a_at,1433819_s 0.4 0.1 0.7 0.4 0.7 _at,1433817_at 233016 Blvrb 1451386_at 0 0.1 0.3 0.4 0.1 13380 Dkk1 1458232_at,1420360_at -0.9 -1.3 0.5 0 -1.4 18010 Neu1 1448481_at,1416831_at,1447942_x_a 1.1 0.2 0.3 1 1.2 t 19368 Raet1a 1420603_s_at -0.5 -0.3 -1.2 -0.6 -1.3 75209 Sv2c 1453715_at -0.4 -2.4 -2.5 -0.8 -2.5 64337 Gng13 1419414_at,1447282_at 0.3 2.7 0.5 2.7 2.3 107746 Rapgef1 1427006_at,1421146_at 0.1 0.2 0 0.2 0.1 229933 Clca5 1438109_at -0.7 1.3 1.9 -0.3 1.4 16188 Il3ra 1419712_at -0.3 -0.1 0.2 0.2 -0.1 78038 Mccc2 1428021_at,1432472_a_at,1454840_a -0.1 0 0.4 0.1 -0.2 t 53413 Exoc7 1434865_a_at -0.2 -0.2 -0.1 0.2 0.2 241226 Itga8 1454966_at,1427489_at 3 0.4 0.1 0.8 0.1 12122 Bid 1447873_x_at,1448560_at,1417045_a -0.2 -0.1 0.6 0.7 0.5 t 19220 Ptgfr 1440777_x_at,1449828_at,1420349_a 3.5 1.1 3.7 1.3 3.3 t,1453924_a_at,1446331_at 108148 Galnt2 1452182_at,1425610_s_at,1426756_a -0.1 -0.1 -0.4 -0.5 0 t 13368 Dffb 1421229_at,1437051_at 0.9 -0.4 -1.2 -0.7 -0.6 70737 Cgn 1435155_at,1430329_at 0.7 0.3 -0.4 -0.5 0 18113 Nnmt 1432517_a_at -0.2 0 -2.7 -2.2 -0.9 12370 Casp8 1424552_at 0.1 0.2 1.1 1.2 0.9 18596 Pdgfrb 1436970_a_at,1417148_at 0.1 0.9 0.9 0.1 -0.2 100048845 LOC100048 1437025_at,1417597_at 0.5 0.8 -0.8 -0.4 1.1 845 19017 Ppargc1a 1456395_at,1460336_at,1437751_at 1 3.3 2.1 0.6 1.5 14814 Grin2d 1421393_at,1442328_at 0.1 0.4 -0.5 -0.2 -0.6 57914 Crlf2 1418097_a_at 0 0 0 0.2 0.4 16885 Limk1 1417627_a_at,1425836_a_at,1456234 0.8 1.1 1.1 0.4 0.5 _at 109785 Pgm3 1428228_at -0.1 -0.3 -0.8 -1 -1.2 11656 Alas2 1451675_a_at 0.1 0.5 1.3 -0.1 -0.3 16643 Klrd1 1460245_at 0.2 0.2 -0.1 0 0.4 140

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 16162 Il12rb2 1421623_at -0.4 0.4 1 1.3 1 13850 Ephx2 1448499_a_at 0.6 0.6 1 0.7 1.3 18475 Pafah1b2 1450755_at,1422791_at,1422793_at, 0 -0.1 0 0 0.1 1422792_at 22321 Vars 1448472_at -0.2 -0.4 -0.9 -4.1 -2 14812 Grin2b 1422223_at,1457003_at,1431700_at 1.8 3 2.3 1.4 0.6 56692 Mapksp1 1416272_at 0.1 0.1 0 -0.1 -0.2 60596 Gucy1a3 1420533_at,1434141_at,1420534_at -0.9 -0.4 -0.2 -0.4 1.7 12274 C6 1449308_at 0.2 1 1.4 0.4 3.2 56274 Stk3 1418513_at,1418512_at,1449114_at 0.6 0.2 0.2 0.4 -0.1 171567 Nme7 1438874_at,1418217_at -0.1 0.7 -0.1 0.1 0.5 20740 Spna2 1427889_at,1427888_a_at 0.1 0.2 -0.1 -0.3 0.3 69772 Bdh2 1453011_at 1.5 3.2 0.2 0 2.5 15560 Htr2c 1450477_at,1435513_at 0.4 0.5 0.3 0 0.5 13026 Pcyt1a 1438011_at,1424453_at,1450434_s_a -0.2 -0.3 0.5 0.6 0.4 t,1421957_a_at 15051 H2-T9 1439121_at,1449875_s_at 0.1 2.5 3.5 4.4 3.8 22177 Tyrobp 1450792_at 0.1 0 0 0.1 0 21939 Cd40 1449473_s_at,1439221_s_at,1460415 0.7 3.6 4.7 5.5 3.2 _a_at 72674 Adipor1 1424312_at,1451311_a_at,1439017_x -0.1 0 -0.2 -0.2 0.4 _at 113868 Acaa1a 1416947_s_at,1416946_a_at,1456737 1.3 0.4 0.5 1.1 0.4 _x_at,1456011_x_at,1424451_at 56175 Bace2 1438645_x_at,1416673_at,1435581_a 0.8 0.4 0.6 0.8 0 t,1437846_x_at 50929 Il22 1427624_s_at -1.4 -2.6 -3.2 -3 -1.8 353371 Oxct2b #N/A 0000 0 12028 Bax 1416837_at 0.1 0 0.2 -0.4 -0.9 11472 Actn2 1448327_at -2.1 0.1 -2.8 -1.8 -3 74245 Ctbs 1427658_at,1429943_at,1452504_s_a -0.2 -0.2 -0.2 0.1 0.6 t 16369 Irs3 1437672_at 0.3 0.2 0 0.4 -0.2 13097 Cyp2c38 1452501_at -0.2 0.1 -1.3 -0.4 -1 14711 Gnmt 1417422_at 0.3 0.4 -0.1 0.3 -0.2 245857 Ssh3 1447929_at 0 -0.4 -0.4 -0.2 0 68977 Haghl 1428584_a_at,1429958_x_at,1428630 0.4 0.1 0.7 -0.8 0.1 _x_at,1433650_at 12576 Cdkn1b 1434045_at,1419497_at 0.1 0.2 0.3 1.1 1 16776 Lama5 1427010_s_at,1459614_at,1427009_a 1.6 2.4 1.5 0.9 2.4 t 55980 Impa1 1423127_at,1430495_at,1436848_x_a 0.3 -0.1 0 0 0.2 t 237928 Phospho1 1452485_at -0.2 -0.2 0.2 -0.6 -0.5 21938 Tnfrsf1b 1418099_at,1448951_at 0 0.3 0.8 1.6 1.5 14173 Fgf2 1449826_a_at -0.3 0.1 -0.3 -1.3 1.4 16777 Lamb1-1 1451241_at,1424113_at,1446180_at, 1.9 1.1 1 3.2 0.4 1424114_s_at 141

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 16403 Itga6 1422444_at,1422445_at -0.3 -0.4 -0.7 -0.7 -1.2 20869 Stk11 1448062_at,1418644_a_at 0.3 2.6 0 0.9 2.3 75533 Nme5 1422727_at -0.4 -0.2 -0.9 -0.9 -1.1 18626 Per1 1449851_at -0.1 -1.7 -0.2 0.5 1 105148 Iars 1452154_at,1426705_s_at 0 -0.2 -1.3 -2.6 -1.5 71755 Dhdh 1453487_at -0.1 -0.6 -1.1 -1.5 -0.1 14528 Gch1 1420499_at,1429692_s_at 0.3 1 1.5 2 1.5 14426 Galnt4 1423638_at,1423637_at,1455915_at 0.1 0.3 1.1 0.1 -0.1 64654 Fgf23 1422176_at 0.1 -0.2 -0.2 -0.5 -2.1 20229 Sat1 1420502_at 0 0.1 0.5 1.3 1 69833 Polr2f 1415754_at,1427402_at -0.1 1.3 1.3 0.7 0.4 75669 Pik3r4 1460352_s_at -0.2 -0.3 -0.2 -0.5 0.2 12826 Col4a1 1426348_at,1452035_at 0.7 -0.4 0 0.1 0 212679 Mars2 1436777_at 0.1 -0.7 -0.7 -4.7 -1.9 18121 Nog 1422300_at -2.9 -3.1 -2.1 -0.7 0.2 54384 Mtmr7 1447831_s_at,1427025_at 0.5 0.8 1.3 1.7 0.8 75320 Etnk1 1454633_at,1430996_at,1439972_at, -0.1 1.6 2.3 2.4 1.7 1433515_s_at,1433514_at 50883 Chek2 1422747_at 0.1 -0.3 -0.7 -1.2 -0.5 20443 St3gal4 1425668_a_at -0.5 -0.8 -1.4 -0.8 -1.3 14177 Fgf6 1427582_at -0.1 3.9 -0.2 0 -0.5 80794 Cblc 1431692_a_at,1422666_at 0.1 2 0.8 1.2 0 22339 Vegfa 1420909_at,1451959_a_at 0.1 -0.7 0 1.2 2.7 23920 Insrr 1420564_at -2.6 -0.9 -0.2 -0.2 -0.3 74987 4930468A1 1431639_at 3.5 0.8 0.8 2.4 0.5 5Rik 21933 Tnfrsf10b 1422344_s_at,1421296_at 0.7 1 1.3 -0.9 -1.3 15970 Ifna7 1450593_at,1422403_at,1422404_x_a 0.5 1.2 4.5 3.5 1.3 t 67087 Ctnnbip1 1417567_at,1431694_a_at 0.2 0.1 -0.6 -0.1 0.5 12183 Bpgm 1415864_at,1448119_at,1415865_s_a 0 -0.5 -0.5 -0.7 -0.2 t 74080 Nmnat3 1432342_at,1424899_at 0 1 -0.2 -0.4 0.1 13117 Cyp4a10 1424853_s_at -0.1 -0.6 -0.1 -0.3 -3.2 207839 Galnt6 1427424_at,1434399_at -0.1 -0.2 -0.5 -0.5 1.1 12667 Chrd 1417304_at -0.1 1.3 0.8 1 -1.5 19207 Ptch2 1422655_at,1457256_x_at 2.3 1.8 2.5 1.4 2.7 19279 Ptprr 1426047_a_at -2 -2.2 0.6 1 -1.4 56386 B4galt6 1460329_at,1423228_at,1450913_at 0.2 0.2 0.3 -0.2 -0.1 26877 B3galt1 1455234_at,1422206_at,1450530_at, 2.8 3.4 4.5 2.7 3.6 1460509_at,1441396_at 225326 Pik3c3 1425580_a_at -0.1 -0.2 0.1 0.1 0.4 16880 Lifr 1454984_at,1425107_a_at,1450207_a 0.5 0.3 0.5 -0.7 -1 t 50880 Scly 1417671_at,1441192_at 0.2 -0.2 0.3 0.1 0.7 142

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 16186 Il2rg 1416295_a_at,1416296_at 0.1 0.1 0.4 0.8 0.9 56469 Pias1 1422581_at,1446448_at,1455486_at, 0.1 0.2 0.6 0.7 0.6 1455611_at 66136 Znrd1 1422517_a_at 0 -0.3 0 0.1 0.5 22154 Tubb5 1455719_at,1416256_a_at 0.1 -0.1 0 -0.2 0.2 76507 Abp1 1424600_at 1.5 0.3 0 1.5 1.4 16180 Il1rap 1449585_at,1439697_at,1421844_at, 0.2 1.1 0.4 -0.2 1.1 1442614_at,1421843_at 16548 Khk 1449062_at -0.1 0.3 -0.6 0 -0.9 20133 Rrm1 1415878_at,1440073_at,1448127_at 0 0.1 -0.2 -1.4 -1.6 14854 Gss 1441931_x_at,1448273_at -0.1 0.1 0.1 -0.4 0.2 18972 Pold2 1448277_at -0.3 -0.5 -1 -1.7 -1.5 15979 Ifngr1 1448167_at -0.1 -0.2 -0.9 -1.4 -0.9 71908 Cldn23 1424409_at 0.8 -0.6 1.6 0.3 2.4 20423 Shh 1436869_at,1427571_at 0.3 0.9 1 0.7 0.4 207182 Ggt7 1451094_at 0.4 0.3 0.9 0.4 0.6 18708 Pik3r1 1451737_at,1425515_at,1438682_at, 0.1 0.4 0.3 0.4 0 1425514_at 66789 Alg14 1419115_at,1419116_at,1419114_at 0.3 0.3 0.3 0.4 0.1 319480 Itga11 #N/A 0000 0 59031 Chst12 1448477_at -0.3 -0.6 -0.9 -0.7 0.6 16331 Inpp5d 1418110_a_at,1424195_a_at -0.1 -0.3 -0.2 -0.5 0.4 12182 Bst1 1449454_at,1449453_at 0.5 0.7 0.6 0.5 0.5 80797 Clca2 1419463_at,1460259_s_at,1437578_a 3.5 4.6 2.4 2.1 2.2 t 100042479 Gm10887 #N/A 0000 0 16192 Il5ra 1421620_at 0.3 0.1 0.3 3.1 1.5 56289 Rassf1 1457788_at,1441737_s_at,1456994_a 0.3 0.3 -0.1 3.5 0.7 t,1448855_at 14174 Fgf3 1441350_at,1422923_at,1441914_x_a 0.4 1.3 1.3 1.9 1.6 t 14430 Galt 1450187_a_at -0.1 -0.3 -0.3 -0.5 0.3 18222 Numb 1425368_a_at,1416891_at 0 0.1 0.4 0.8 0.7 11566 Adss 1460726_at 0 0.1 -0.4 -1 -0.6 11816 Apoe 1432466_a_at 0.3 -2 -3.2 0.7 -3.3 20655 Sod1 1435304_at,1451124_at,1447761_x_a 0.1 0.2 2.9 1.6 2.1 t,1459976_s_at 70881 Nt5c1b 1427715_a_at -0.3 -0.1 0.6 -0.5 0.4 241113 Prkag3 #N/A 0000 0 20775 Sqle 1415993_at 0 -0.3 -1.4 -2.5 -1.6 23972 Papss2 1421989_s_at,1421988_at,1434510_a -0.1 0 0.2 0.1 -0.6 t,1421987_at 22376 Was 1419631_at -0.1 -0.1 -0.4 -0.3 0 67883 Uxs1 1426275_a_at,1452011_a_at 0.4 0.3 0.2 -0.1 -0.2 12035 Bcat1 1450871_a_at,1430111_a_at,1455699 0.2 0 0.1 -0.1 0.6 _at 107589 Mylk 1425505_at,1425506_at,1425504_at 2.3 2.5 1.8 2.3 2.5 143

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 18588 Pde6g 1425100_a_at,1450453_a_at 1.5 1.2 0.3 2.1 -0.5 14176 Fgf5 1438883_at,1426186_a_at 0.4 0 0.7 1.1 2.9 72094 Ugt2a3 1450133_at 1.1 0.6 1.3 1.1 -1.3 17387 Mmp14 1448383_at,1440920_at,1416572_at 1.4 1.5 1.8 1.6 0.1 231991 Creb5 1440089_at,1442576_at,1457222_at 1.5 1.1 2.2 1.7 1.1 21877 Tk1 1416258_at 0.3 0.1 -0.4 -4.3 -5.3 18605 Enpp1 1419276_at,1459546_s_at,1440339_a 0.3 0 -0.4 -0.6 -0.2 t 30938 Fgd3 1454593_at,1433398_at,1450235_at 0.8 0.4 0.2 0 0.5 18414 Osmr 1418674_at,1459217_at,1418675_at 4.3 5.1 2.2 0.8 1.6 11677 Akr1b3 1448319_at,1437133_x_at,1456590_x -0.1 0 0.1 -0.1 -0.3 _at 50930 Tnfsf14 1421588_at,1450298_at 0 -0.1 -2.1 -2 -2.1 18747 Prkaca 1450519_a_at,1447720_x_at -0.2 -0.1 -0.4 -0.4 0.1 17883 Myh3 1427115_at -0.5 -0.2 -0.2 0.2 -0.8 230379 Acer2 1451355_at,1421496_at 2.5 0.4 2.4 0.2 -0.1 244349 Myst3 1437487_at,1436315_at,1446405_at 0.7 0.4 0.7 0.5 0.3 16774 Lama3 1444860_at,1427512_a_at 1.3 0.4 0 0.7 0.8 19697 Rela 1419536_a_at 0 0.4 0.5 0.5 0.5 70686 Dusp16 1440615_at,1418401_a_at 1.2 1 1.1 0.6 0.8 56484 Foxo3 1434832_at,1434831_a_at,1450236_a 1 1.3 0.7 0.2 1.1 t,1444226_at 22418 Wnt5a 1456976_at,1448818_at,1436791_at 1.3 0.4 1.7 -0.8 0.9 11433 Acp5 1431609_a_at 0 0 0.1 0.9 2.9 231327 Ppat 1452831_s_at,1441770_at,1428543_a 0.2 2.4 2.9 2.2 1.7 t 71884 Chit1 1453844_at 0.2 0.4 -0.2 -0.1 0 244416 Ppp1r3b 1436590_at -0.1 -0.8 -1 -0.5 0.6 114715 Spred1 1423160_at,1428777_at,1423161_s_a 1.5 3.5 0.8 1.5 1.1 t,1452911_at,1460116_s_at,1443652_ x_at,1423162_s_at,1445228_at 19264 Ptprc 1422124_a_at,1440165_at 0.2 0.2 0.3 0.3 -0.2 11555 Adrb2 1437302_at 0.1 -1 -1.6 -1.6 -1.5 14182 Fgfr1 1425911_a_at,1424050_s_at,1436551 0.4 1 -0.1 -0.3 0.2 _at 353148 Tas2r139 #N/A 0000 0 14167 Fgf12 1451693_a_at,1440270_at 1.2 1.8 1.3 0.9 0.8 14595 B4galt1 1418014_a_at 0.1 -0.2 -0.3 -0.2 0.1 16401 Itga4 1427615_at,1421194_at,1450155_at, 0.5 1.3 1.8 1.7 0.3 1456498_at,1436037_at 11951 Atp5g1 1444874_at,1416020_a_at 1.7 3 2.7 -0.2 0.1 20449 St8sia1 1455695_at,1419694_at,1419695_at 1.1 1.2 2.1 2.5 2 56811 Dkk2 1420512_at -2.7 -3.4 -0.5 -4.1 -2.3 433158 Gm5500 #N/A 0000 0 74915 Atp6v1e2 1450552_at 0 0.3 -0.4 0.5 0.2 14180 Fgf9 1438718_at,1420795_at 0.4 1.1 1.2 1.2 1.9 144

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 387512 Tas2r135 #N/A 0000 0 12445 Ccnd3 1444323_at,1415907_at,1438805_at 0 -0.2 -0.4 -0.1 0.3 14673 Gna12 1439206_at,1421026_at,1450097_s_a 0.8 0.5 0.2 0.2 0.1 t,1450096_at 15487 Hsd17b3 1421671_at 0.8 0.3 0.3 0.7 -3.5 242316 Gdf6 #N/A 0000 0 17886 Myh9 1420171_s_at,1440708_at,1417472_a 0.1 0.1 0.1 0.2 -0.3 t,1420170_at 207565 Camkk2 1455401_at,1424476_at,1424474_a_a 0.3 0.2 0.4 0.3 0.5 t,1424475_at 66052 Sdhc 1435986_x_at,1448630_a_at 0 -0.1 -0.2 -0.2 -0.3 66420 Polr2e 1451093_at,1417138_s_at,1458326_a 0 0.2 0.2 0.5 2.4 t 23939 Mapk7 1418060_a_at -0.2 -0.7 -0.2 0.1 0.3 15558 Htr2a #N/A 0000 0 76238 Grhpr 1417772_at 0 -0.3 -0.7 -2 0.1 16159 Il12a 1425454_a_at 1.5 2.1 3.2 4 0.8 15186 Hdc 1454713_s_at,1451796_s_at 0 1 4.8 5.6 4.4 11514 Adcy8 1418754_at -0.5 1.9 -0.3 1.4 -0.7 11867 Arpc1b 1416226_at,1416227_at 0.1 -0.1 0 -0.1 0 394430 Ugt1a10 1426261_s_at,1426260_a_at,1424783 -0.1 0.2 -0.1 -0.3 0.7 _a_at 140491 Ppp1r3a 1422108_at 0.8 3.4 2.9 3 1.9 22423 Wnt8b 1441316_at,1421439_at,1421440_at 1.1 1 3.4 0.3 0.3 11937 Atp2a1 1419312_at -0.1 -0.3 -0.4 -0.3 -0.5 26413 Mapk1 1426585_s_at,1453104_at,1419568_a 0.3 0.4 0.2 -0.3 0.2 t 17874 Myd88 1419272_at 0.1 0.6 1 0.9 0.2 18815 Plg 1416729_at 2.2 0.4 2.1 1.7 2.5 60525 Acss2 1457460_at,1422478_a_at,1422479_a 0.2 0.2 0.5 0.6 1 t,1446542_at 58861 Cysltr1 1418944_at,1449282_at 0 0.1 1 0.6 0.2 12982 Csf2ra 1420703_at,1420704_at 0.2 0 0.1 0.1 0.2 12361 Cask 1422519_at,1427692_a_at,1422518_a 0 0.2 0.8 0.9 0.4 t,1455406_at 75560 Ep400 1440751_at,1426860_at,1449610_at, 2.3 1.5 3 0.8 0.2 1441630_at,1453130_at,1447712_x_a t,1447349_s_at,1437020_at 109778 Blvra 1428580_at 0 -0.1 -0.3 -0.6 -0.6 26399 Map2k6 1426850_a_at 1.9 1.3 1.4 0.1 2.5 170744 Tlr8 1450267_at -0.3 0.1 0.9 1.2 1.3 338403 Cndp1 1455561_at -0.1 3 -0.2 1.9 -0.4 226139 Cox15 1426693_x_at,1460376_a_at,1452146 0 0.6 0.9 0.6 0.2 _a_at,1437982_x_at 12870 Cp 1417495_x_at,1417494_a_at,1417497 3 1.6 3.3 3.5 3.5 _at,1417496_at,1448734_at,1455393 _at,1441326_at,1448735_at 14158 Fert2 1421729_a_at,1426090_a_at -0.3 0.3 -0.5 0.5 0.3 145

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 11429 Aco2 1436934_s_at,1451002_at -0.1 -0.1 -0.2 -0.3 -0.1 19664 Rbpj 1418114_at,1448957_at,1454896_at 0 0 0.1 0.2 -0.7 223864 Rapgef3 1424470_a_at,1437946_x_at,1437012 0.5 1.6 1 0.4 3 _x_at,1424471_at,1438590_at 15492 Hsd3b1 1448453_at 1 3.8 -0.2 0.2 0.6 27007 Klrk1 1450495_a_at -0.1 1.2 2.5 4.1 3 105349 Akr1c18 1419136_at -0.1 0.2 -0.2 -1.6 -3.7 27375 Tjp3 1417896_at 0.2 0.2 0 0.4 0.5 12517 Cd72 1426112_a_at -0.2 0 0.4 1.1 1.7 18183 Nrg3 1460289_at,1421017_at 0.6 0.3 0.2 0.3 -0.4 20852 Stat6 1426353_at,1421708_a_at 0 -0.1 0.2 0.3 0.6 18103 Nme2 1448808_a_at 0.1 0.1 0.1 -0.1 -0.7 63828 Fn3k 1418311_at,1442436_at 0.2 0.4 0.5 4.3 2.5 12296 Cacnb2 1452476_at,1456401_at 0.7 0.7 5.4 4.5 4.4 67574 Alg13 1418681_at 0 -0.1 -0.3 -0.7 -1.5 23844 Clca3 1416306_at,1459889_at 3.4 3.8 2.7 2.1 3.1 17475 Mpdz 1442978_at,1441361_at,1418664_at, 0.2 0.4 0 0.9 -0.2 1418663_at 226414 Dars 1423800_at -0.1 -0.2 -0.7 -2 -0.9 81904 Cacng7 1426336_at,1439745_at -0.1 1.2 0 1.1 0 22323 Vasp 1451097_at 0 -0.1 -0.3 -0.6 -1.1 12091 Glb1 1416205_at,1435795_at,1437159_at -0.1 0 -0.2 0 0.2 67755 Ddx47 1438381_x_at,1423752_at,1438380_a -0.2 0.1 0.3 -0.3 0.2 t 15978 Ifng 1425947_at -0.1 0.4 -2.7 -0.6 -0.2 20014 Rpn2 1418896_a_at -0.2 -0.1 -0.4 -0.4 -0.7 20704 Serpina1e 1449321_x_at -0.2 0 0.4 -0.2 -1.2 19645 Rb1 1417850_at,1444400_at 0.3 0.4 -0.5 -0.8 0.5 109079 Sephs1 1433974_at,1454792_s_at,1455511_a 0.7 0.1 0.5 0.5 -0.5 t,1433973_at 54420 Cldn8 1449091_at -0.8 -1.3 -2.3 -2 -1.6 69215 Sat2 1430318_at -1.8 0.5 -1.5 -0.3 -2.1 270685 Mthfd1l 1456653_a_at -0.1 -0.1 -0.4 -1.1 -0.1 235339 Dlat 1426264_at,1452005_at,1426265_x_a 0 0 -0.1 -0.6 -0.1 t 171212 Galnt10 1418194_at,1418195_at,1440493_at 0.1 0.3 0.2 0.6 0.3 12391 Cav3 1418413_at -1.1 -1 1.6 0.1 -2 74769 Pik3cb 1453069_at 0.1 -0.1 0.1 0.2 -0.4 70383 Cox10 1429329_at,1435380_at,1459977_x_a 0 0.1 -0.3 0.1 -0.3 t 20361 Sema7a 1459903_at,1422040_at 1.9 2.2 2.2 3.4 2.3 102580 Alg9 1418844_at,1430420_at 0.2 0.4 0.1 1.4 0.5 52815 Ldhd 1428614_at,1428613_at 0.2 0.4 -0.7 0.7 0.3 17346 Mknk1 1417630_at,1454119_at,1417631_at 0.1 -0.2 0 -0.5 0.4 67092 Gatm 1423569_at -0.1 -0.1 -0.1 -1 -3.4 146

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 70405 Calml3 1418608_at -0.2 -1 0.6 0.8 -0.4 18709 Pik3r2 1418463_at,1453984_at 0.7 0.9 -0.7 0.2 0.5 432530 Adcy1 1445359_at,1456487_at 1.2 0.4 2.3 2.5 1.9 20663 Sos2 1452281_at 0 -0.3 -0.3 -0.2 -0.1 76654 Upp2 1424969_s_at,1451548_at,1460059_a 2.5 0.2 3.7 4.2 1.4 t 23917 Impdh1 1423239_at -0.1 -0.1 -0.5 -0.4 0.2 54167 Icos 1421930_at,1436598_at,1421931_at 0.9 3 0.4 0.7 1.7 16634 Klra3 1425436_x_at 0.2 0.6 0.5 0.8 0.8 71832 Csl 1449400_at 0 -1.7 -2.6 -2.4 -2.2 53313 Atp2a3 1450124_a_at,1421129_a_at 0.9 0.9 0.6 -0.4 -1.2 12703 Socs1 1450446_a_at,1440047_at 0.7 3 3.4 3.3 1.9 18751 Prkcb 1443144_at,1423478_at,1460419_a_a -0.1 -0.2 -0.2 -0.6 -0.6 t 54378 Cacng6 1451811_at,1425730_at 0.5 0.7 2.2 1.3 0.5 14538 Gcnt2 1430826_s_at,1437607_at,1450238_a 2.8 3.5 3.7 2.9 2.8 t,1421415_s_at,1425503_at,1451733_ at,1453674_at,1438660_at 14317 Ftcd 1419670_at -0.7 0.3 0 -1 0.4 59001 Pole3 1421015_s_at,1452743_at,1459816_x 2.3 0.7 -0.6 2.3 1.5 _at 229658 Vangl1 1427234_at 0.4 0.5 -1.2 -0.3 -0.3 13643 Efnb3 1423085_at -1 0.2 0 0.3 -3 233046 Rasgrp4 1425380_at 0.3 -0.9 0.2 -1.2 -2 21355 Tap2 1453913_a_at -0.1 0.4 1.3 2 1.9 13089 Cyp2b13 1449479_at 0.2 0.3 0.5 2.2 -0.1 13897 Es22 1419510_at -0.5 0.7 -1.1 -0.8 0.8 14137 Fdft1 1448130_at,1438919_x_at,1438918_a 0.1 0.7 -0.8 0.9 -1.2 t,1438322_x_at 23921 Sh2b2 1450718_at,1453389_a_at 0.2 0.2 0 -0.1 2.1 11522 Adh1 1416225_at 2.1 0.5 -0.1 2.2 0.2 64143 Ralb 1417744_a_at,1435517_x_at 0 -0.3 -0.6 -0.3 -0.3 14871 Gstt1 1418186_at 2.1 1.6 1.1 3.8 1.9 12116 Bhmt 1450624_at -0.8 -0.2 0.6 0.5 0.4 13077 Cyp1a2 1450715_at -0.9 -0.9 -0.8 1.5 -0.8 19091 Prkg1 1449876_at,1444232_at 0.2 1 0.4 -0.1 0.9 11946 Atp5a1 1420037_at,1449710_s_at,1423111_a 0.2 0.1 0.2 0.1 -0.1 t 227753 Gsn 1415812_at,1437171_x_at,1436991_x 0 0 -0.1 0.1 -0.3 _at,1456568_at,1456569_x_at,145631 2_x_at 13122 Cyp7a1 1438743_at,1422100_at 0.7 0.6 0.9 2.9 0.6 11611 Agxt 1418833_at 0.1 -0.8 0.3 0.5 0.1 16790 Anpep 1421424_a_at -0.1 0 0.1 0.9 1.5 53412 Ppp1r3c 1433691_at,1425631_at 1.4 0.6 0.3 0.1 0.4 26405 Map3k2 1422250_at,1438719_at,1455597_at 0 -0.2 -0.5 0 0.1 147

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 23872 Ets2 1416268_at,1447685_x_at,1437809_x 0.1 0.5 -0.1 0.4 0.4 _at 435889 #N/A 1415954_at 0.7 0.2 -0.1 -0.3 2 320951 Pisd 1439070_x_at,1435425_at,1436944_x 0.5 0.1 -0.2 0 0.4 _at,1435426_s_at,1460585_x_at,1426 387_x_at 17393 Mmp7 1449478_at -0.1 0.9 -1.5 0.3 -2 50784 Ppap2c 1420910_at,1451210_at -0.1 0.2 0.7 0 0.3 12505 Cd44 1443265_at,1434376_at,1452483_a_a 2.1 1.7 1.9 0.8 0.8 t,1423760_at 16150 Ikbkb 1445141_at,1426333_a_at,1432275_a 0.2 0.5 0.4 0.8 0.5 t,1426207_at,1454184_a_at 14380 G6pd2 1422327_s_at,1422326_at -0.1 -0.2 0 0.3 0.5 21787 Tfg 1438053_at,1415887_at 0.2 0.5 0.7 0.9 0.3 97212 Hadha 1452173_at -0.3 -0.1 -0.1 0.1 0.2 67054 Paics 1423565_at,1423564_a_at,1436298_x -0.1 -0.1 -0.5 -1.6 -1.2 _at 17705 ATP6 #N/A 0000 0 110651 Rps6ka3 1452383_at,1427299_at -0.1 0.1 -0.1 -0.2 -0.6 14701 Gng12 1455089_at,1421947_at 0 0 0.2 0.4 0.2 210044 Adcy2 1455462_at 0.6 0.9 0.6 0 0.3 14938 Gzma 1417898_a_at -0.3 -0.6 0.1 0.2 -0.5 15000 H2-DMb2 1418638_at,1449580_s_at,1443687_x 0.2 0.2 0.1 0.1 -0.3 _at,1443686_at,1419744_at 19225 Ptgs2 1417262_at,1417263_at 2.2 3.3 4.7 6.3 1.6 21372 Tbl1x 1434643_at,1434644_at 0 0.3 0.3 0.4 0.3 16370 Irs4 1441429_at,1422248_at 0.7 -0.2 -0.1 0.5 -0.1 15001 H2-Oa 1419297_at 0 0.3 0.8 2.1 2.8 57260 Ltb4r2 1450807_at -0.6 1.7 -0.2 3.3 1.7 108155 Ogt 1451738_at,1425516_at,1436780_at, 0.6 -0.1 0 -0.3 -0.1 1460631_at,1425517_s_at 17885 Myh8 1426650_at -2.2 -0.3 -1.9 -1.5 -1.6 16154 Il10ra 1456173_at,1448731_at,1437808_x_a 0.6 1.4 1.4 1.3 0.5 t 58226 Cacna1h 1422710_a_at,1427607_at -0.2 0.4 0.3 -0.2 0.4 11676 Aldoc 1424714_at,1451461_a_at -0.1 -0.1 -0.2 -0.9 -1.9 16409 Itgam 1422046_at -0.2 -0.3 -0.3 -0.4 -0.7 54218 B3galt4 1419138_at -0.3 -0.2 0.2 0.5 1.3 14870 Gstp1 1449575_a_at 0 -0.1 -0.3 -0.7 -0.2 104015 Synj1 1439997_at,1454961_at,1436333_a_a 0.6 0.5 1 0.8 0.7 t,1436334_at 16411 Itgax 1419128_at 0.1 0 0 0 -0.2 29863 Pde7b 1421353_at,1445539_at,1450213_at 3.9 3.4 5 5.6 4.7 13095 Cyp2c29 1417651_at 0.5 -0.2 0.3 0.4 -0.9 67305 Gpx7 1417836_at 0.2 -0.2 -0.1 -0.2 0.3 22095 Tshr 1421999_at,1442300_at,1428001_at 0.5 2.4 2.6 0.7 -0.2 71960 Myh14 1428835_at 0.3 0.2 -0.3 0 -0.5 148

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 18126 Nos2 1420393_at 0.1 0.6 5 7.9 6.8 18127 Nos3 1422622_at -0.1 0.1 0.1 -0.5 0.7 18704 Pik3c2a 1421023_at,1425862_a_at,1443655_s -0.1 -0.3 -0.5 -1 -1.2 _at 16176 Il1b 1449399_a_at 2.1 1.9 1.2 1.9 -1.4 209590 Il23r #N/A 0000 0 21838 Thy1 1423135_at 0.6 0.1 0 -0.3 -1.3 17329 Cxcl9 1418652_at,1456907_at 0.6 6.5 7.4 7.9 7.4 30956 Aass 1423523_at 0 0.3 -2 -2.8 -2.2 12287 Cacna1b 1425812_a_at,1436602_x_at,1460608 0.4 0 -0.4 0 -0.4 _at,1439612_at 16780 Lamb3 1417812_a_at 0.4 -0.3 -1 -0.1 0.5 13086 Cyp2a4 1422230_s_at 3.1 2.7 -0.1 -0.2 2.8 54419 Cldn6 1417845_at 0.2 0 -1.4 -1.7 -1.6 14165 Fgf10 1420690_at 1.8 0.1 3.4 3.7 2.7 17127 Smad3 1450472_s_at,1454960_at,1450471_a 0 0.5 0.2 0.4 0.3 t 329278 Tnn 1442140_at 1.8 0.2 0.1 1.5 -0.5 240168 Rasgrp3 1438031_at,1438030_at 0.4 -0.2 0 -2.5 -2.7 13844 Ephb2 1454022_at,1425016_at,1425015_at -0.1 0.2 0 0.2 1.5 110557 H2-Q6 1431008_at,1451644_a_at 0.7 1.1 2.1 3 5.1 12266 C3 1423954_at -0.1 0.2 0.6 1.2 1.2 15466 Hrh2 1423639_at -0.4 0.2 1.1 1.4 0.8 78929 Polr3h 1424227_at,1424228_at 0.3 0.3 -0.2 -0.3 -0.1 15962 Ifna1 1450564_x_at,1422404_x_at,1450593 0.5 1.2 4.5 3.5 1.3 _at,1422403_at 22414 Wnt2b 1421465_at -0.6 -0.8 -0.5 0.6 0.5 384061 Fndc5 1453135_at,1435115_at 0 0 -0.4 -0.2 -0.7 73181 Nfatc4 1423380_s_at,1423379_at,1454369_a 1 1.4 2.1 1.2 0.1 _at,1432821_at 12359 Cat 1416430_at,1416429_a_at -0.1 0 -0.3 -0.5 -0.2 12974 Cs 1422577_at,1422578_at,1450667_a_a 0 0.1 0 -0.3 -0.2 t 23923 Aadat 1418519_at -0.9 1.8 -1 2.5 -0.4 67895 Ppa1 1416939_at -0.1 0.1 0.6 0.7 -0.2 230815 Man1c1 1436193_at 0 -0.1 -0.3 -0.3 0.3 67993 Nudt12 1453139_at -0.4 -0.4 -1.3 -1.3 -1 236539 Phgdh 1456584_x_at,1426657_s_at,1456471 0.4 0.4 1.4 0.5 0.8 _x_at,1454714_x_at,1437621_x_at,14 32707_at,1426658_x_at 15497 Hsd3b6 1460232_s_at -1.5 -0.2 1.1 -0.4 0 15968 Ifna5 1450593_at,1422403_at,1450614_x_a 0.8 1.2 4.7 4.7 1.3 t,1422404_x_at 12286 Cacna1a 1444455_at,1459996_at,1450510_a_a 1.5 1.4 2.3 1.4 1.8 t,1430408_at 14130 Fcgr2b 1435477_s_at,1455332_x_at,1435476 0 -0.3 -0.7 -0.8 -0.2 _a_at,1451941_a_at,1447622_at 54200 Sult2b1 1417335_at 0.9 -1.1 -1.1 0 1 149

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 17096 Lyn 1451318_a_at,1425598_a_at 0 -0.1 0.6 0.6 -0.1 22030 Traf2 1451233_at 0.1 0.3 0.5 0.7 0.8 18817 Plk1 1448191_at -0.3 -0.1 -0.9 -1.5 -3.9 14368 Fzd6 1458904_at,1448662_at,1417301_at 3.1 1.5 2.8 2.5 0.9 18481 Pak3 1435486_at,1437318_at,1417924_at, 1.1 0.5 0.2 1.2 0.6 1417923_at 26879 B3galnt1 1418736_at -0.3 -0.2 -0.5 -0.4 0.1 107141 Cyp2c50 1418653_at -1.1 1 -1.6 -2 -2.8 13085 Cyp2a12 1418821_at 0.2 0.4 3.3 1.4 0.8 56441 Nat6 1449954_at,1419213_at 0.3 0.5 0.7 0.9 1.2 231148 Ablim2 1435441_at,1455313_at 0.6 0.5 0.6 0.6 0.8 16770 Lalba 1418363_at 0.7 0.7 0.5 0.4 0.1 17129 Smad5 1451873_a_at,1421047_at,1433641_a 0.1 0 -0.5 0 -0.7 t 17125 Smad1 1459843_s_at,1448208_at,1416081_a 0.2 0.5 0.5 0.5 0.2 t 67909 Galntl5 1417641_at 0.2 1.7 -1.9 -1.1 1.2 81004 Tbl1xr1 1457186_at,1434839_s_at,1442312_a 0 0.2 0.1 0.1 2 t,1422761_at,1450739_at,1455109_at

226251 Ablim1 1442376_at,1454708_at,1453103_at, 0.1 2.1 1.5 0.5 1.5 1460120_at 20779 Src 1423240_at,1450918_s_at 0.2 1.3 1.3 1.9 2 107029 Me2 1426573_at,1458172_at,1426572_at -0.2 0 -0.5 -0.9 -0.4 64339 Fndc4 1431226_a_at,1449012_s_at -1.9 -1 0.8 0.7 0.2 15024 H2-T10 1439121_at,1449875_s_at 0.1 2.5 3.5 4.4 3.8 20603 Sms 1421052_a_at,1434190_at,1428699_a 0.1 0.3 0.5 0.9 -0.2 t 15368 Hmox1 1448239_at 0.1 0.5 0.3 0.4 1.3 18761 Prkcq 1426044_a_at 0.3 0.4 0.2 0.3 -0.2 18973 Pole 1448650_a_at 0.5 0.3 -1.4 -1.4 -5.2 320302 Glt28d2 1455455_at -0.1 0.5 -0.3 0.5 -0.6 15042 H2-T24 1422160_at -0.2 0.9 2.3 3.1 3.1 12298 Cacnb4 1452089_at,1436912_at,1428928_at 1 2 4 5.4 6.5 56185 Hao2 1418654_at 0.7 2.1 0.8 0.3 0.8 22271 Upp1 1448562_at 0.1 -0.1 0.1 0.7 -1.8 102093 Phkb 1434511_at -0.1 -0.1 0 0.1 0.2 20319 Sfrp2 1448201_at 1.1 -1.1 0.6 0.6 0.8 103236 Csnk1g2 1423370_a_at -0.1 -0.1 -0.7 -0.8 0 13197 Gadd45a 1449519_at 0.9 -0.9 -1.8 -1.8 -0.4 56636 Fgf21 1422916_at 0 -0.3 0 2 2.3 76025 Cant1 1421476_a_at,1451688_s_at,1433709 0 -0.2 0.2 0.7 0.9 _at 381314 Iars2 1426735_at,1441665_at -0.1 0 -0.5 -0.5 -0.5 216456 Gls2 1435245_at -2.5 -1.2 -1.7 0.4 -1.1 13807 Eno2 1418829_a_at -0.2 -1.4 -2.3 -0.3 -1 150

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 15170 Ptpn6 1456694_x_at,1460188_at 0 0 1 1.6 1.2 26414 Mapk10 1458513_at,1448342_at,1437195_x_a 0.4 0 1.4 3.3 1 t 19210 Ptdss1 1449739_at,1416372_at,1441866_s_a 0 0.1 0.6 0.4 1.7 t 235293 Sc5d 1434520_at,1424709_at,1451457_at 0.1 0 -0.6 -0.5 -0.3 19046 Ppp1cb 1426205_at,1456462_x_at,1433540_x 0 0.1 0 0.1 0 _at,1431328_at 18733 Lilrb3 1420464_s_at,1424302_at 0 0 0.4 1.1 1 319448 Fndc3a 1458524_at,1426903_at,1443863_at 0 0 0.8 1.3 0.7 13846 Ephb4 1449845_a_at 0.1 0.1 -0.3 0.4 -0.5 16765 Stmn1 1415849_s_at,1448113_at -0.1 0.2 0 -1.3 -2.7 30955 Pik3cg 1422707_at,1422708_at 0 -0.6 -1.2 -1.7 -0.5 22245 Uck1 1424399_at -0.2 -0.4 -0.7 -0.5 0.3 16641 Klrc1 1425005_at,1426182_a_at 3.2 0.4 5.1 4.8 3.9 69564 Itgb1bp3 1453898_at -2 -1.5 -1.8 -1.6 -0.6 20302 Ccl3 1419561_at 0.4 0.3 0.3 0.4 -3.6 13016 Ctbp1 1415702_a_at -0.1 -0.1 -0.2 -0.7 -0.5 320981 Enpp6 1438785_at,1436090_at -0.7 -0.1 0 -0.3 0.7 17164 Mapkapk2 1426648_at 0 0.6 0.8 1.2 0.7 19188 Psme2 1417189_at -0.1 0.5 0.9 1.6 1.4 170835 Inpp5j 1433941_at 0.2 0.3 -0.1 0.1 -0.3 12293 Cacna2d1 1449999_a_at,1441608_at,1425861_x 2.2 2.5 3.1 0.6 2.9 _at,1433643_at,1440397_at 234130 Dkk4 1425447_at 0.8 0 0.5 -1.5 0.3 12640 Cga 1418549_at 0 0.5 0 0 -0.8 56752 Aldh9a1 1436689_a_at,1437398_a_at 0 0 -0.3 -1 -0.3 192176 Flna 1426677_at -0.1 -0.1 -0.2 -0.5 -1.5 17448 Mdh2 1433984_a_at,1416478_a_at 0 0 0 -0.1 0.4 216033 Ctnna3 1441560_at 0 0.1 0.1 0.8 -0.4 21682 Tec 1460204_at 0.1 -0.7 -0.3 -0.6 0 18613 Pecam1 1421287_a_at 0.3 0.1 -0.3 0.2 -0.2 74351 Ddx23 1430050_at,1439952_at 0.4 -0.6 -0.2 -0.5 -0.9 218832 Polr3a 1437525_a_at,1434453_at,1444310_a 0.1 -0.2 -0.3 -0.1 0 t 16410 Itgav 1452784_at,1432679_at,1421198_at, 0.7 2.5 1.3 1.6 0.4 1432296_a_at,1432678_at 52585 Dhrs1 1415677_at -0.2 -0.3 -0.2 -0.5 0.7 69719 Cad 1440857_at,1452830_s_at,1452829_a 0 -0.2 -0.8 -1.1 -1.9 t 16407 Itgae 1447541_s_at,1449216_at -0.2 0.9 1.1 0.4 0.5 17131 Smad7 1443771_x_at,1423389_at -0.1 -0.3 0 -0.1 0.3 15285 Mnx1 1460299_at 1 -1.4 -1.6 -1.5 -1.1 387346 Tas2r114 #N/A 0000 0 14991 H2-M3 1421358_at 0.2 0.3 0.9 1.4 1.4 13191 Dctn1 1422521_at,1435414_s_at -0.1 0 -0.1 -0.2 -0.1 151

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 18609 Pdx1 1422173_at,1422174_at 0.2 0.5 0.1 0.5 0.3 108664 Atp6v1h 1457639_at,1447659_x_at,1415826_a -0.1 0 0.7 1.1 -0.1 t 18682 Phkg1 1425164_a_at -0.2 0.4 0.1 0 -0.5 19053 Ppp2cb 1421823_a_at -0.1 -0.2 0 -0.3 -0.6 108150 Galnt7 1426908_at,1425581_s_at,1452232_a -0.1 0 0.7 0.8 0.3 t 12715 Ckm 1417614_at 1 2.4 -0.2 0 2 53323 Ube2k 1417188_s_at,1417187_at,1443148_a 0.3 0.6 0.4 0.1 1.5 t,1417186_at 239559 A4galt 1455338_at 0.3 0.3 0.2 0.4 0.1 13663 Ei24 1416555_at -0.2 -0.2 -0.6 -0.9 -0.6 320769 Prdx6-rs1 1437412_at,1447715_x_at 0.3 0.4 1.4 0.3 0.5 17330 Minpp1 1455787_x_at,1423265_at,1429750_a 0.1 0.4 0.8 1.1 0.8 t 12709 Ckb 1455106_a_at -0.3 -0.1 -0.1 -0.5 0.4 22413 Wnt2 1449425_at 0.1 0.9 3.4 0.3 1.6 67112 Fgf22 1460296_a_at,1450205_at -0.6 -1.4 0.4 0.5 0.5 230103 Npr2 1427191_at 1.1 0.9 -0.1 1.6 0.5 224129 Adcy5 1447696_x_at,1455296_at,1443080_a 0.9 0.8 0.8 0.3 0.6 t,1439829_at 213435 Mylk3 1439101_at 1.7 1 1.7 1.1 1.3 22031 Traf3 1449149_at,1418587_at 0.2 0.3 0 0.6 0.6 13590 Lefty1 1417638_at -0.9 -3.4 -3.6 -3.7 -3.7 13867 Erbb3 1452482_at,1434606_at 0.5 0.2 0.4 0.2 1.1 14319 Fth1 1448771_a_at,1427021_s_at 0.2 0.1 0.4 0.3 0.5 57423 Atp5j2 1435395_s_at,1443495_at,1416269_a 0 -0.1 -0.2 -0.2 -0.2 t 236576 Spry3 1438073_at -1.4 -0.6 -0.2 -2.9 -2.7 66138 Wbscr22 1423575_a_at 0 -0.2 -0.5 -0.8 -0.7 54131 Irf3 1435271_at,1426111_x_at,1416898_a 0.4 -0.4 -0.1 0.2 0.1 _at,1438721_a_at 12716 Ckmt1 1432418_a_at,1417089_a_at -1.3 0.5 0.8 -0.3 0.5 64705 Dpys 1436291_a_at,1425689_at,1425688_a 2.2 0.4 0.8 1.2 2.2 _at 20303 Ccl4 1421578_at 0.6 0.7 1 0.9 -2.5 11648 Akp3 1450572_at -0.2 -0.1 -2.3 -1.5 0.4 12408 Cbr1 1460196_at -0.1 -0.4 -0.4 -0.3 0.8 14120 Fbp2 1449088_at 0.1 -0.1 0.3 0.8 -0.1 14164 Fgf1 1423136_at,1450869_at,1441042_at 0.6 0.2 0 0.2 1.6 18618 Pemt 1450612_a_at 0 0.1 -0.1 -0.5 -0.9 53972 Ngef 1448978_at 0.3 0.3 3.3 1.8 0.2 268510 Mgat5b 1434531_at -0.3 1.7 0 0.2 0.1 56324 Stam2 1453338_at,1416975_at,1416976_at, 0.3 0.3 0.3 0.8 0.4 1416977_at,1440034_at,1416974_at

16890 Lipe 1422820_at 0 0.3 1 0.9 0.4 152

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 19719 Rfng 1421160_a_at,1460704_at 0.1 0.1 -0.1 -1.1 0.2 18597 Pdha1 1449137_at,1418560_at -0.1 -0.1 -0.3 -1 -0.8 56388 Cyp3a25 1424973_at 0.2 0.3 1.1 0.6 0.4 19186 Psme1 1417056_at 0 0.2 0.8 1.3 1.6 15512 Hspa2 1417101_at 0.5 0.2 0.1 0 -0.3 12631 Cfl1 1455138_x_at,1448346_at 0.1 0 0.1 0.1 0 60363 Cldn15 1418920_at 0.1 0.3 -0.1 0.4 0 72590 Ppme1 1423810_at -0.1 -0.2 -0.5 -0.4 0.2 18205 Ntf3 1434802_s_at,1450803_at 4.5 0.2 -0.2 2.6 0.2 19765 Ralbp1 1448634_at,1417248_at -0.1 0 -0.3 -0.4 0.2 16151 Ikbkg 1421209_s_at,1435646_at,1454690_a 0 0.2 0.7 0.4 0.6 t,1421208_at,1450161_at,1435647_at

110197 Dgkg 1419756_at,1431167_at,1449584_at 2.5 1.4 2.8 2.5 2.4 16147 Ihh 1450704_at -0.7 -0.1 -0.1 0.3 -1.2 13849 Ephx1 1422438_at -0.2 0 -0.1 -0.8 -0.1 224912 Crb3 1424809_at,1455115_a_at,1434851_s 1.5 2.2 1.4 0.7 0.4 _at 56449 Csda 1451012_a_at,1435800_a_at 0 0 -0.2 -0.8 -1.7 11864 Arnt2 1420670_at,1434028_at,1420669_at 0.4 0.8 0.6 1.1 0.6 71147 Oxsm 1419973_at,1429699_at,1449685_s_a 0.3 0.6 0.7 0.8 0.1 t,1449684_at,1455395_at 76355 Tgds 1424526_a_at -0.1 -0.2 -0.3 -0.2 -0.2 381924 Itgad #N/A 0000 0 14065 F2rl3 1421288_at 0.1 -0.1 -1.4 0.6 -0.6 19092 Prkg2 1435460_at,1421354_at,1435162_at 0.6 1.2 0.7 0.7 0.4 15107 Hadh 1460184_at,1436756_x_at,1455972_x -0.2 0.1 -0.1 -0.8 -0.2 _at 109264 Me3 1429071_at -1.1 -0.7 1.7 1.2 1.8 12229 Btk 1422755_at 0 -0.4 0 -0.4 0 53623 Gria3 1420563_at,1434728_at 1.2 1.7 0.6 0.3 1.5 15114 Hap1 1416997_a_at 0.3 0.6 0.5 0.6 -0.4 18979 Pon1 1418190_at 0.2 -1.5 -0.5 -2 0.1 13640 Efna5 1436866_at,1421796_a_at 0.4 1.8 2 -1.8 1.4 11655 Alas1 1455282_x_at,1424126_at 0.1 0 0 0.3 0.4 17156 Man1a2 1420977_at,1420976_at,1456534_at, 1.4 0.2 3.4 3.3 2.8 1434395_at 18046 Nfyc 1448963_at -0.1 -0.1 -0.4 -0.6 -0.4 108841 Rdh13 1433799_at 0 -0.3 -1 -0.7 -0.1 52538 Acaa2 1428146_s_at,1455061_a_at,1428145 0 -0.2 -0.3 -0.6 -0.2 _at 104776 Aldh6a1 1448104_at -0.1 -0.3 -0.7 -0.6 -0.4 76282 Gpt 1426502_s_at,1453216_at 0.3 0.1 -0.8 0.3 0.3 19418 Rasgrf2 1440918_at,1421621_at 0.2 0.2 0 0.4 0.2 18160 Npr1 1449160_at 0 -2.4 0.1 -2 0 237823 Pfas 1455496_at 0.3 0 -1.1 -2.3 -1.3 153

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 23971 Papss1 1415890_at -0.2 -0.2 -0.3 -0.6 -0.6 67834 Idh3a 1447701_x_at,1432016_a_at,1422500 0 0.1 0.3 0.3 0.3 _at,1422501_s_at 14058 F10 1418992_at,1418993_s_at,1449305_a 0.2 0.4 0.6 0.8 0.6 t 71785 Pdgfd 1446691_at,1456532_at,1426319_at 1.3 0.7 1 1.3 0.4 16476 Jun 1448694_at,1417409_at 0.6 0 0.2 -0.2 0.5 71941 Cars2 1431778_at,1428524_at,1454186_a_a 1.4 1.5 1.7 1.5 0.2 t 11430 Acox1 1416409_at,1416408_at,1444518_at 0.2 -0.3 -0.4 -0.4 -0.2 23882 Gadd45g 1453851_a_at -0.9 -0.5 -0.5 -0.1 1.1 17130 Smad6 1422771_at -0.2 0.6 0.4 0.4 0 170767 Rfxap 1455303_at,1418859_at 0 -0.3 -0.4 -0.8 0.1 13822 Epb4.1l2 1459619_at,1433491_at,1433490_s_a 2.3 3 2.8 0.3 0.4 t,1433492_at,1452541_at 20019 Polr1a 1447597_at,1417775_at,1460215_at, 2.3 0.5 3 2.1 3.3 1456066_a_at,1447598_x_at 15972 Ifna9 1422404_x_at,1460611_at,1422406_a 0.5 1.5 4.5 6 1.3 t,1422403_at,1450593_at 13637 Efna2 1444606_at,1417521_at 2.7 1.4 3.6 4.2 3.1 14367 Fzd5 1455604_at,1422937_at -0.2 0.4 1.1 0.7 -0.3 18452 P4ha2 1417149_at -0.1 0.8 0.3 2.4 2.4 19109 Prl 1429287_a_at 0.4 1.6 0.1 -0.5 1.3 53608 Map3k6 1449901_a_at -0.3 -0.1 -1.2 -1.2 -1.1 234734 Aars 1451083_s_at,1423685_at -0.1 0 0.1 0.1 1.1 14963 H2-Bl 1447260_at,1450531_at 0 0.3 0.7 0.7 0.8 170743 Tlr7 1422010_at,1419848_x_at,1449640_a 0.2 0.6 1.3 1.5 1.5 t 20598 Smpd2 1416999_at -0.6 -3.2 -0.4 -0.1 0.5 22033 Traf5 1447682_x_at,1448861_at 0.1 0.3 0.6 0.9 -0.2 12048 Bcl2l1 1420887_a_at,1426191_a_at,1426050 0 -0.5 0 0 -0.5 _at,1420888_at 12829 Col4a4 1425772_at,1445328_at,1440250_at -0.2 0.5 0.7 2.4 -0.1 68214 Gsto2 1453708_a_at -0.4 -3.3 -1 -0.7 -0.2 16500 Kcnb1 1423179_at,1417810_a_at,1458270_a 0.7 0.1 2 0.4 -0.1 t,1423180_at 382053 Es31 1451600_s_at 0.2 0.5 -0.4 -0.2 -2.4 15379 Onecut1 1456974_at,1450252_at,1421447_at 1.5 1.3 2.3 3 1.6 68465 Adipor2 1434329_s_at,1437864_at -0.1 -0.3 -0.3 -0.4 0.1 70789 Kynu 1451903_at,1430570_at 0.7 1.8 3.7 4.6 2.9 78070 Cpt1c 1435281_at 0.1 -0.1 0.1 0.1 -0.2 17060 Blnk 1451780_at -0.2 -0.1 0.6 0.9 1.6 20544 Slc9a1 1417397_at -0.1 0.1 0.4 0.4 0.7 20400 Sh2d1a 1449393_at 0.7 -0.1 4.2 0.9 1.1 381903 Alg8 1455887_at -0.1 -0.2 -0.8 -1.1 -1.5 11799 Birc5 1424278_a_at 0.1 0.3 -0.4 -1.5 -1.8 12815 Col11a2 1423578_at 0.3 0.8 0.3 0.1 0.4 154

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 67916 Ppap2b 1429514_at,1448908_at 0.1 1.1 1.8 2.8 2.8 11905 Serpinc1 1417909_at -0.1 0.2 0.5 0.4 -0.3 19057 Ppp3cc 1420743_a_at,1430025_at -0.1 -0.2 -0.7 -0.8 -0.7 13135 Dad1 1418528_a_at,1454860_x_at 0 0.1 -0.1 -0.9 -1 14252 Flot2 1417544_a_at,1438164_x_at 0.1 0 -0.2 -0.2 0.3 239931 Cldn17 #N/A 0000 0 26419 Mapk8 1420932_at,1440856_at,1457936_at, 2.1 2.3 2.8 1.7 0.3 1437045_at,1420931_at 59048 C1galt1c1 1416655_at,1443706_at 2 0 1.9 1.5 2.1 108105 B3gnt5 1420993_at,1420994_at 2.4 3.1 3.9 3.5 3.7 16816 Lcat 1417043_at 0.7 0.4 0.5 -0.1 -0.7 19309 Pygm 1448602_at 0.2 1.2 0 0 -0.3 15194 Htt 1425969_a_at,1446337_at,1456667_a 0.6 -0.2 0.1 0.3 -0.3 t 22275 Urod 1417206_at,1443849_x_at -0.1 0 -0.2 -0.5 0.1 19099 Mapk8ip1 1425679_a_at,1440619_at -0.1 0.4 -0.3 -0.8 -1.9 20148 Dhrs3 1448390_a_at -0.1 -0.1 -0.6 -0.5 1 11670 Aldh3a1 1418752_at -0.1 0.1 0 -0.6 -0.1 229615 Pias3 1451115_at,1421646_a_at 0 -0.1 0.4 0.3 0.9 192156 Mvd 1417303_at,1448663_s_at 0.1 -0.2 -0.5 -0.3 0.5 104099 Itga9 1460285_at,1450029_s_at,1420860_a 0.6 2 0 0.4 0.2 t 16450 Jag2 1426430_at,1426431_at 0.6 0.3 -0.6 0.8 0.1 16412 Itgb1 1426920_x_at,1426918_at,1452545_a 3.8 3.6 4.1 3.8 0.7 _at,1427771_x_at,1438119_at,142691 9_at 14997 H2-M9 1450529_at 0.9 -0.7 1 0.8 1.4 20442 St3gal1 1441216_at,1418946_at 0.6 0.5 1 1.6 0.6 12700 Cish 1448724_at 0.9 0.8 0.8 0.7 -0.6 16428 Itk 1417171_at,1457120_at,1456836_at, 4.7 0.5 2.9 4.2 2 1452518_a_at,1430833_at 22032 Traf4 1416571_at,1460642_at 2.7 1.9 2.1 1.5 0 55948 Sfn 1448612_at -0.1 0.1 0.8 0.3 0.4 26398 Map2k4 1426233_at,1451982_at 0.1 0.1 0 0.1 -0.4 20787 Srebf1 1426690_a_at -0.1 -0.2 -0.5 -0.5 -0.2 241159 Neu4 #N/A 0000 0 20971 Sdc4 1417654_at,1448793_a_at 0.7 2.2 1.9 2.4 0.1 78284 Creb3l4 1424218_a_at 0.6 -1.6 -1.3 -2.1 -3.5 14431 Gamt 1422558_at -0.3 -0.2 -0.6 -0.7 -0.4 22390 Wee1 1416774_at,1416773_at 0.2 -0.1 0.1 0.3 0.5 110542 Amhr2 1457021_x_at,1427989_at,1438967_x 0.1 0.6 0.4 0.6 0.4 _at 106557 Ldhal6b 1434247_at 0 0.2 0 0 -0.3 18582 Pde6d 1416843_at -0.2 -0.2 0.1 0.7 0.5 268697 Ccnb1 1449675_at,1419943_s_at,1448205_a 1.9 0.3 0 1.2 2.4 t,1416076_at,1419944_at 155

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 238871 Pde4d 1459311_at 1 -2.1 -2.8 -0.6 -2.2 69536 Hemk1 1424703_at,1430287_s_at 0.1 0.1 0.3 -0.2 -0.8 17246 Mdm2 1427718_a_at,1457929_at,1423605_a 0.2 0.4 1 1.6 1.2 _at 13544 Dvl3 1420457_at 0 0.2 -0.4 0 -0.2 12288 Cacna1c 1421297_a_at -1.9 0 0.1 -0.1 -2.5 17001 Ltc4s 1419692_a_at -0.1 -0.1 -0.3 -0.3 0.1 387348 Tas2r120 #N/A 0000 0 107747 Aldh1l1 1424401_at,1424400_a_at 0.1 0.6 1 1.8 1.6 56554 Raet1d 1420603_s_at -0.5 -0.3 -1.2 -0.6 -1.3 57342 Parva 1431375_s_at,1416818_at 0.6 0.5 0.5 0.5 1.8 16155 Il10rb 1419455_at 0 0.1 0.5 0.8 0.9 67689 Aldh3b1 1452301_at -0.1 -0.1 -0.1 -0.5 0.2 574417 Tas2r137 #N/A 0000 0 75477 Pfn3 1453962_at -0.3 -2.2 -0.6 -1.8 -1.8 12499 Entpd5 1417384_at,1417383_at,1433763_at, 0 -0.1 0 0.4 0.2 1458677_at,1451765_a_at,1417382_a t 12390 Cav2 1417327_at,1425955_at 0.4 0 -0.2 0.2 -0.5 22018 Tpo 1420600_at 0.1 -2 0.8 0.2 -0.7 14270 Srgap2 1427967_at,1429884_at,1434406_at, 0.2 0.3 1.2 1 0.4 1434407_at 72054 Cyp4f18 1433389_at,1419219_at 0 -0.2 -0.5 -0.9 0.6 18777 Lypla1 1453949_s_at,1431607_at,1448244_a 0.1 0 -0.1 0 -0.4 t 24063 Spry1 1415874_at 1.1 0.8 0 -0.1 -1 20703 Serpina1d 1449321_x_at -0.2 0 0.4 -0.2 -1.2 14810 Grin1 1437968_at,1450202_at 1.1 1.1 1.1 2.5 0.1 16202 Ilk 1449942_a_at -0.2 -0.2 0 0 -0.1 13857 Epor 1423344_at 0.3 -0.2 -3.1 -0.7 -0.5 237860 Ssh2 1455078_at,1456153_at 0.3 -0.2 -1 -1.4 -0.7 12156 Bmp2 1423635_at 0.8 4.4 4.3 4.9 0.2 20848 Stat3 1460700_at,1459961_a_at,1424272_a 0.4 0.6 0.7 1.1 1.3 t,1426587_a_at 228139 P2rx3 1425093_at,1458396_at 0.4 0 0.2 0.1 0.1 74747 Ddit4 1428306_at 0.6 0.3 -0.6 1.6 2 13837 Epha3 1455426_at,1426057_a_at,1425574_a 0.8 1.8 2 1.7 5.6 t,1425575_at 18263 Odc1 1438761_a_at,1427364_a_at,1437711 -0.1 0.2 -0.7 -1.2 -1.1 _x_at 14423 Galnt1 1423236_at,1423237_at -0.1 -0.1 -0.4 -0.6 -0.5 140481 Man2a2 1457498_at,1435203_at 0.4 -0.5 -0.7 -1.4 -0.8 109700 Itga1 1439713_at,1455251_at -0.1 0 -0.2 -1 -2 12630 Cfi 1418724_at -0.6 -1.2 0.4 0.5 -0.6 56044 Rala 1456049_at,1450870_at,1423137_at 2.7 0.2 0.1 0.3 2 80904 Dtx3 1420752_at 0.6 -0.2 0.2 -0.3 0.3 156

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 74519 Cyp2j9 1424677_at 0.4 -1.8 -1.3 0.6 0.2 16416 Itgb3 1421511_at,1455257_at 0 -0.2 -1 0.3 0.1 20860 Sult1e1 1420447_at -1.5 -2.2 -1.7 -2.2 -2.6 100042419 Trav7d-3 #N/A 0000 0 271639 Adcy10 1439613_at -1.5 -0.4 1.2 -0.5 0.8 22409 Wnt10a 1460657_at 0.4 1.2 -0.1 1.9 0.6 140781 Myh7 1448554_s_at,1448553_at,1448827_s 1.6 2.9 0.7 0.7 0.2 _at 192185 Nadk 1416248_at,1416249_at 0 0 -0.2 -0.7 -1 12043 Bcl2 1443837_x_at,1457687_at,1437122_a 0.6 -0.2 0.2 -0.8 -0.9 t,1440770_at,1422938_at 68703 Rere 1454670_at,1439159_at 0 -0.4 -0.6 -0.5 0.8 14874 Gstz1 1427552_a_at -0.9 -0.9 -1.1 -0.9 -0.7 73341 Arhgef6 1429012_at,1442292_at -0.1 -0.2 -0.7 -0.3 -0.8 18641 Pfkl 1450269_a_at,1453541_at,1439148_a 0 -0.3 0 0.2 1 _at 15930 Ido1 1420437_at -0.4 -0.6 -0.1 -0.3 -0.1 17961 Nat2 1449981_a_at 0 1 1.8 1.6 1.2 68263 Pdhb 1416090_at,1448214_at 0.2 0 0 -0.2 0.1 56336 B4galt5 1421967_at,1433617_s_at 2.1 2.3 2.7 2.7 2.5 66925 Sdhd 1428235_at,1437489_x_at 0 0 -0.2 -0.5 0.1 18417 Cldn11 1416003_at 0.2 0.5 -1.6 0.8 -0.5 18793 Plaur 1452521_a_at 0.1 -0.1 0.1 0.2 -0.2 17762 Mapt 1424718_at,1424719_a_at,1455028_a 0.7 2.5 0.8 0.9 1.4 t,1417885_at 19419 Rasgrp1 1434295_at,1421176_at,1431749_a_a 0.6 0.9 1.1 2.2 -0.2 t,1450143_at 17199 Mc1r 1422069_at,1435393_at 2.8 0.9 0.6 1.3 1.8 11911 Atf4 1438992_x_at,1448135_at,1439258_a 0.2 0.3 0.2 0.5 0.7 t 22375 Wars 1425106_a_at,1437832_x_at,1415694 0 0.1 0.9 1.5 1.6 _at,1434813_x_at 19417 Rasgrf1 1424734_at,1459056_at,1422600_at, 1.2 2.7 3 2.3 2 1435614_s_at 73166 Tm7sf2 1460684_at 0.2 0.2 0.4 0.2 -0.4 100678 Psph 1415673_at 0.1 -0.1 -0.3 -0.1 0.3 387341 Tas2r106 #N/A 0000 0 16194 Il6ra 1452416_at,1422270_a_at 0.4 0 0 0.1 0.4 12064 Bdnf 1422168_a_at,1422169_a_at -0.1 -1.4 1.1 0.7 2.1 99586 Dpyd 1427945_at,1443717_at,1427946_s_a 1.3 2.1 0.9 1.2 1.6 t 22410 Wnt10b 1426091_a_at 0 0.3 0.2 0.2 -0.6 230828 Il22ra1 #N/A 0000 0 18770 Pklr 1438711_at,1421259_at,1421258_a_a 0.4 0.1 -0.1 0.3 0 t 14281 Fos 1423100_at -0.1 0.2 1 1.2 2.2 56749 Dhodh 1417582_s_at,1417581_at -0.2 -0.2 -0.5 -1.2 -0.4 157

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 15101 H60a 1457769_at,1440145_at 3.4 1.8 1.9 3.8 1.1 225010 Lclat1 1434690_at -0.2 -0.1 -0.4 -0.9 -0.5 17309 Mgat3 1428801_at,1422145_at,1428802_at 1.2 1.2 2 0.3 -0.3 54721 Tyk2 1417306_at 0 0.2 0.7 1.4 0.8 14617 Gjd2 1435297_at,1423019_at 1.1 1.7 1.4 1.4 2.3 404195 Cyp2c54 1455457_at 0.2 0.5 -0.7 0.7 -2.3 11370 Acadvl 1424184_at 0 -0.1 -0.3 -0.8 -0.2 72930 Ppp2r2b 1426621_a_at 1.9 2.5 1.5 3.1 2 18506 Pax4 1451598_at 0.3 0.3 1.2 0.3 1.3 12695 Inadl 1442244_at,1418983_at,1418984_at, 1.3 0.6 2.7 2.5 0.7 1440737_at 286940 Flnb 1445534_at,1442107_at,1426750_at, 3.4 3.8 3.1 3.8 1 1458226_at 50518 a 1420516_at -0.1 -0.1 0.1 0.6 -0.4 22241 Ulk1 1448370_at,1416504_at -0.3 0 -0.3 -0.1 0.9 70428 Polr3b 1443466_s_at,1452949_at,1443494_a 0.3 -0.1 0 -0.3 -0.2 t 12894 Cpt1a 1434866_x_at,1438156_x_at,1460409 -0.2 0.2 0.4 0.3 0.5 _at 20441 St3gal3 1421915_a_at,1450406_a_at 0.1 0.6 0.6 1 0.6 19229 Ptk2b 1442927_at,1434653_at 0 0.2 0.7 1 1.4 216443 Mars 1455951_at 0 0.1 -0.4 -1.3 0 67967 Pold3 1459647_at,1443733_x_at,1426839_a 0.4 -0.1 0 0.4 0.6 t,1426838_at 50877 Neu3 1419339_at 0.2 -0.2 -1.6 0.5 0.8 73086 Rps6ka5 1431050_at,1440343_at,1439004_at 0.6 0.8 0.3 0.4 -0.4 19058 Ppp3r1 1450368_a_at,1421786_at,1433591_a 0.1 0.1 0.2 -0.2 0 t 14936 Gys1 1450196_s_at,1416737_at 0.3 -0.4 -1.2 -2.4 1.3 13542 Dvl1 1450978_at,1437301_a_at 0.3 -0.2 -0.3 -0.7 -0.4 66073 Txndc12 1415738_at -0.1 -0.1 -0.2 0 0.5 14678 Gnai2 1419449_a_at,1435652_a_at 0.1 0.2 0.2 0.3 0.8 72508 Rps6kb1 1457562_at,1454956_at,1459951_at, 0.9 0.4 -0.2 0 0.1 1428849_at,1460705_at,1446376_at

12292 Cacna1s 1420442_at -2.1 -1.6 -0.1 -1.4 -1.8 15233 Hgd 1452986_at,1458049_at 0.6 0.6 0.8 3.3 2.3 18242 Oat 1416452_at -0.1 -0.2 -0.3 -1.1 -1.3 13098 Cyp2c39 1421363_at 0.5 3.3 0.3 0.3 -0.3 14283 Fosl1 1417487_at,1417488_at 0.5 -0.6 -1.2 -1.3 -1.1 18754 Prkce 1437861_s_at,1452878_at,1449956_a 0 0.2 0.6 0.7 2.1 t,1437860_at 20851 Stat5b 1422102_a_at,1422103_a_at 0 0.2 0.4 0.6 0.3 14972 H2-K1 1424948_x_at,1425336_x_at,1450534 0.2 0.5 0.4 2 3.9 _x_at,1451593_at,1427746_x_at 18049 Ngf 1419675_at 0.2 2.7 0.4 3.5 0.4 19744 Rheb 1416636_at 0 -0.1 -0.2 -0.3 -0.3 158

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 228966 Ppp1r3d 1452922_at -0.3 -0.7 -1.2 -1.3 -0.9 387345 Tas2r113 #N/A 0000 0 74596 Cds1 1456114_at,1428680_at 0 0.2 1.5 1.7 0.9 14968 H2-Ea 1422892_s_at,1426202_at,1422891_a 1.4 0.4 0 0.4 0 t 16184 Il2ra 1420691_at,1420692_at 0.5 0.5 0.7 2 1.2 20438 Siah1b 1419404_s_at 0 -0.3 -0.5 -0.2 -0.6 16420 Itgb6 1422983_at,1432281_a_at 0.6 1.3 3.1 0.6 3.9 11821 Aprt 1423801_a_at,1451703_s_at -0.2 -0.1 -0.4 -0.6 -0.5 675747 LOC675747 #N/A 0000 0

56717 Mtor 1436267_a_at,1446185_at,1417592_a 2.1 0.1 0 1.3 0.2 t 19354 Rac2 1417620_at,1440208_at 0.1 -0.2 -0.4 -0.7 0.2 18712 Pim1 1423006_at,1435458_at 0.9 0.8 0.9 1.2 0.9 20975 Synj2 1452344_at,1431697_at,1427685_a_a 0.2 1 0.4 0.1 0 t,1425217_a_at,1427652_x_at,143182 8_a_at 18293 Ogdh 1445632_at,1451274_at 0.2 -0.1 -0.3 -0.5 0.1 18211 Ntrk1 1443990_at 0.2 0.9 0.5 -0.5 -0.6 58179 Klrc3 1421794_at,1421795_s_at 0.2 0.4 0.5 0.9 2.9 74637 Shpk 1452853_at -2.9 -2.6 -3.1 -3 0.8 229665 Ampd1 1434722_at 2 0.4 -0.1 0.1 -0.2 67942 Atp5g2 1447714_x_at,1456128_at,1415980_a 2.2 1.4 0.7 1.8 1.9 t 14857 Gsta1 1421041_s_at -0.2 0.6 1.1 1.8 3.1 67464 Entpd4 1431761_at,1447900_x_at,1438177_x -0.1 -0.1 -0.6 -1 -0.6 _at,1449190_a_at 109880 Braf 1435434_at,1445786_at,1442749_at, 0.2 0.2 0.3 0.4 0.3 1447941_x_at,1447940_a_at,1456505 _at,1425693_at,1435480_at,1458641 _at 12740 Cldn4 1418283_at -1.9 -0.1 -1.8 -1.5 -0.9 70086 Cysltr2 1421642_a_at 0.5 0.4 1.1 1.7 2.5 12927 Bcar1 1439388_s_at,1450622_at 0.2 0.4 0.2 0.5 -0.1 12411 Cbs 1425623_a_at,1423844_s_at 0.9 2.6 1.2 2.8 0.4 26395 Map2k1 1416351_at 0 0.3 0.9 1.4 1.1 12504 Cd4 1419696_at,1427779_a_at 1.8 0.3 0.7 2.7 0.6 15182 Hdac2 1449080_at,1445684_s_at,1439704_a 0.1 -0.1 -0.7 -0.7 -1 t 72198 Skiv2l2 1437971_at,1447517_at,1426718_at 0.2 0 0.3 1.4 -0.4 16828 Ldha 1419737_a_at 0.1 0 0 0.1 0.5 229211 Acad9 1429581_at,1453206_at,1444394_at 0.6 0.1 0.5 0.2 1 19401 Rara 1450180_a_at 0.2 0.1 0 -1.7 0 387511 Tas2r134 #N/A 0000 0 22420 Wnt6 1435980_x_at,1419708_at 0 0.3 0 0 -0.2 11898 Ass1 1416239_at,1459937_at 0.2 0 0.1 0.3 0.4 159

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 12369 Casp7 1448659_at,1426062_a_at 0 0.2 0.9 1.4 0.5 18216 Ntsr1 1420799_at -1.4 -1.7 -0.5 -2 0.3 14555 Gpd1 1456732_at,1416204_at,1448249_at, 0.6 0.2 0.4 0.1 0 1439396_x_at 14169 Fgf14 1449958_a_at,1435747_at 0.2 0.8 -0.1 0.2 1.6 16326 Inhbe 1422144_at 0.2 -0.5 -0.7 -1.1 1 70791 Hars2 1449371_at,1419158_a_at 0.2 -0.1 -0.4 -0.3 0.3 12267 C3ar1 1419483_at,1419482_at,1442082_at 0 -0.4 0.6 1.2 2.5 13836 Epha2 1421151_a_at 0.4 0.3 0.1 0 -0.4 67980 Gnpda2 1457230_at,1426524_at,1426523_a_a 0.2 0.2 0.2 0.1 0.5 t 26412 Map4k2 1428297_at,1450244_a_at,1434833_a 0 0.1 0.1 0 0.1 t 14864 Gstm3 1427474_s_at,1427473_at -0.2 0.3 1.4 0.4 0.6 18663 Pgk2 1416784_at -2.1 -1.5 -1.1 -1.4 -0.8 20671 Sox17 1429177_x_at,1421657_a_at 3.9 0.9 0 -0.1 2.2 387354 Tas2r129 #N/A 0000 0 72303 Cyp2c65 1429994_s_at -1.1 -2.1 -0.9 -0.7 0.3 12367 Casp3 1449839_at,1430192_at,1426165_a_a 0.1 1.2 1.8 2.6 2 t 11608 Agtr1b 1446527_at 1.8 2.1 3.8 3 -0.1 14718 Got1 1450970_at -0.2 -0.2 -0.4 -0.1 1.3 19224 Ptgs1 1436448_a_at,1423414_at 0.2 0 -0.4 -1.9 -1.1 11541 Adora2b 1434772_at,1450214_at,1434431_x_a 0.7 0.2 0.9 0.3 -0.6 t,1434430_s_at 69888 Cyp2c66 #N/A 0000 0 19088 Prkar2b 1430640_a_at,1456475_s_at,1438664 0.1 0 -0.6 -1.1 0.1 _at 11754 Aoc3 1449396_at -0.2 0.1 0 0.2 0 11972 Atp6v0d1 1415671_at -0.1 0 0 0.3 0.3 320634 Ocrl 1438396_at,1457313_at,1438284_at 0.3 -0.2 0.1 0.2 0 18643 Pfn1 1449018_at 0 0.1 0.1 0.1 -0.8 107568 Wwp1 1427097_at,1452299_at,1427098_at -0.1 -0.1 -0.4 -0.8 -0.4 12386 Ctnna2 1448895_a_at 2.1 1.9 2.4 1.3 1.5 104174 Gldc 1416049_at 0.1 0.3 0.4 0 3 12525 Cd8a 1425335_at,1451673_at,1440811_x_a 0.8 1.2 0.9 1 0.8 t,1440164_x_at,1444078_at 57265 Fzd2 1418533_s_at,1418534_at,1418532_a 0.6 1.1 3 0.7 2.6 t 14704 Gng3 1417428_at 0.9 0.8 -0.2 0.9 0 15277 Hk2 1422612_at 0.2 0.2 0.5 1 0.5 22637 Zap70 1440178_x_at,1422701_at,1439749_a 3.1 3.7 1.9 1.5 0.3 t 12895 Cpt1b 1418328_at 0.6 -0.3 0.8 -0.3 -2.4 94284 Ugt1a6a 1424783_a_at,1426260_a_at,1426261 -0.1 0.2 -0.1 -0.3 0.7 _s_at 54354 Rassf5 1422637_at,1422638_s_at -0.2 -0.4 -0.7 -1 -0.4 160

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 11441 Chrna7 1450299_at,1440681_at 0.2 -0.6 -0.5 0.8 -0.9 12160 Bmp5 1421282_at,1455851_at,1421283_at 0.7 0.6 1.4 1.1 2.6 80857 Fgf20 1421677_at 2.2 -0.1 1.9 1.8 1.2 387513 Tas2r138 #N/A 0000 0 239556 Cacna1i #N/A 0000 0 269643 Ppp2r2c 1438054_x_at,1443804_at,1438671_a 0.6 0.2 0.2 0.9 -0.2 t 80911 Acox3 1437352_at,1420684_at 0.5 -0.1 0 0.2 0.3 12159 Bmp4 1422912_at 1.6 1.8 1.8 1.7 -0.2 320910 Itgb8 #N/A 0000 0 22421 Wnt7a 1458334_at,1447647_at,1423367_at 1.7 1.6 1.2 1.7 1.2 67126 Atp5e 1416567_s_at 0 0 0.1 0.2 -0.3 108760 Galntl1 1416760_at 0.2 0.3 0.1 0.8 0.3 14083 Ptk2 1440082_at,1443384_at,1430827_a_a 0.2 0.2 0.2 0.7 0.2 t,1423059_at 15288 Hmbs 1436930_x_at,1426475_at -0.2 -0.4 -1.3 -1.5 -0.7 23900 Hcst 1419119_at -0.1 0 0.1 -0.1 0.2 12506 Cd48 1427301_at -0.2 -0.1 0 -0.1 -0.6 66940 Shisa5 1437503_a_at,1423986_a_at 0 0.1 0.4 0.7 1.4 18640 Pfkfb2 1431901_a_at,1422092_at,1429486_a 0.9 0.6 0.5 0.8 0.1 t,1422090_a_at,1422091_at 66234 Sc4mol 1423078_a_at,1459627_at 0.1 -0.3 -1.1 -1.5 -0.8 22629 Ywhah 1416004_at -0.1 0 0 0.1 0.2 17260 Mef2c 1421028_a_at,1421027_a_at,1451506 0.2 0.4 1.1 0.1 0.5 _at,1424852_at,1451507_at 20437 Siah1a 1419404_s_at,1423390_at,1449733_s 0.2 0.1 0.3 0.1 -0.2 _at,1420106_at 20375 Sfpi1 1418747_at 0 -0.1 0.1 0.5 0.4 11848 Rhoa 1443768_at,1437628_s_at,1450632_a 0 0 0 0.4 0.2 t 103534 Mgat4b 1424720_at -0.1 -0.4 -0.5 -0.3 0.2 14161 Fga 1424279_at 1.9 3.2 0.6 -0.6 0.2 17898 Myl7 1449071_at 0.4 0.8 2.8 1.5 0.9 16440 Itpr3 1417297_at 0.1 -0.1 -0.7 -1.2 0.5 68794 Flnc 1447812_x_at,1449073_at -0.6 -0.2 -1.3 -1.6 -2.4 54126 Arhgef7 1424482_at,1449066_a_at 0.9 0 -0.1 -0.3 -0.2 114141 Cldn16 1420434_at -3.1 -0.4 -2.8 -3.1 -2.8 21844 Tiam1 1418057_at,1453887_a_at,1444373_a 0.8 0.2 0.6 -0.6 -0.6 t 625249 Gpx4 1451695_a_at,1456193_x_at 0 0 0.2 0.2 0.4 218461 Pde8b 1435741_at,1437989_at -0.1 0 0.6 1.2 2.1 14924 Magi1 1427246_at,1458240_at,1451893_s_a 0.4 3.2 1.1 0.8 3.7 t,1440871_at,1452369_at,1440071_at

11974 Atp6v0e 1416328_a_at 0 0 0.1 0.3 0.5 161

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 22059 Trp53 1457623_x_at,1459781_x_at,1427739 2 1.5 3.5 0.4 1.5 _a_at,1426538_a_at,1459780_at,143 8542_at,1438808_at 223722 Mcat 1452216_at 0.1 -0.2 0 -0.5 -0.3 353166 Tas2r117 #N/A 0000 0 67486 Polr3g 1449155_at -0.4 -0.5 -3.1 -4.9 -4.2 11687 Alox15 1420338_at -1.4 -0.7 -0.3 -2.5 -3.1 17449 Mdh1 1438338_at,1434319_at,1436834_x_a 0.1 0.3 0.4 0.4 0.5 t,1454925_x_at,1448172_at 110524 Dgkq 1437000_at -0.1 0.1 -0.2 0.1 0.4 77974 Rdh12 1424256_at,1431010_a_at -0.2 0.9 2 0.7 3.1 331026 Gmppb 1439030_at -0.1 -0.3 0.5 0.8 0.4 12387 Ctnnb1 1450008_a_at,1430533_a_at,1420811 0 0 -0.1 -0.1 0.2 _a_at 76263 Gstk1 1452823_at 0.3 0.1 0.1 -0.1 0 15496 Hsd3b5 1420531_at 0.3 0.5 0.4 0.6 0 16399 Itga2b 1417758_at 0.4 0.4 0.3 0.2 0.1 17888 Myh6 1448827_s_at,1417729_at,1448554_s 0.2 3.7 0.8 2.2 0.6 _at,1448826_at 223920 Soat2 1460722_at -1.8 -1.1 -1.2 -2 0.9 67041 Oxct1 1449059_a_at,1428140_at,1436750_a 0 0.3 0.1 0 0.2 _at,1455804_x_at 387344 Tas2r110 #N/A 0000 0 22612 Yes1 1418470_at,1456843_at,1458878_at, 2.5 2.5 2.9 2.3 3.7 1449090_a_at 66586 Crls1 1431930_x_at,1429737_a_at 0 -0.2 -0.6 -1.1 -0.4 14683 Gnas 1453413_at,1443375_at,1450186_s_a 0 0 0.2 0.3 1.5 t,1421740_at,1427789_s_at 12984 Csf2rb2 1450200_s_at,1449360_at 0.2 0.2 0.5 0.4 0.9 13139 Dgka 1418578_at 0 0.2 0.8 1.1 0.4 16175 Il1a 1421473_at 1.9 1.4 1.8 2.2 -0.6 13856 Epo #N/A 0000 0 79059 Nme3 1448905_at 0.1 -0.1 -0.2 -0.4 -0.8 14163 Fgd1 1416865_at,1437369_at 3.6 1.2 0 0.8 3.1 18969 Pola2 1456713_at,1448369_at,1425794_at 0 0.2 -0.2 -0.2 -0.3 26912 Gcat 1417824_at,1417823_at 0 0.4 2.4 3.1 0.1 216963 Git1 1454759_at 0.1 -0.6 -0.2 0.3 1 76113 Lpo 1448998_at 0.2 0.7 2.2 0.6 1.9 22419 Wnt5b 1439373_x_at,1422602_a_at 0.6 0.3 0.9 0.8 1.5 66894 Wwp2 1438482_at,1442162_at,1448145_at, 1.8 0.9 0.6 1.3 1.4 1456714_at,1457499_at,1448146_at

14680 Gnal 1442021_at,1439957_at,1446359_at 0.8 1.9 2 2.4 2.5 68312 Gstm7 1419072_at,1425946_at 0.9 1 0.3 0.7 0.5 16897 Llgl1 1416621_at -0.2 0 0.4 0.5 0.8 16323 Inhba 1422053_at,1458291_at 0.6 0.7 0.9 1.4 0.8 162

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 19216 Ptger1 1445445_s_at,1436851_at,1450491_a 0.4 0.5 0.4 0.7 1.5 t 12478 Cd19 1450570_a_at 0.2 0.3 0.5 0.3 -0.1 242519 Ifna12 1450593_at,1422403_at,1422404_x_a 0.5 1.2 4.5 3.5 1.3 t 20016 Polr1c 1449648_s_at,1417041_at 0.1 -0.3 -0.5 -0.6 -0.2 18780 Pla2g2a 1450128_at 0.8 1.3 0.6 1.2 0.7 29857 Mapk12 1449283_a_at,1447823_x_at 1.9 2.3 2.3 3.2 0.3 20445 St6galnac1 1421517_at -1.1 -0.2 -1.5 -0.1 -1.6 231086 Hadhb 1437172_x_at,1442732_at,1426522_a 0.2 0 0.1 -0.2 0.2 t 22630 Ywhaq 1420828_s_at,1460621_x_at,1437608 0.6 0.1 0.3 0.5 -0.5 _x_at,1420829_a_at,1420830_x_at,14 32842_s_at,1436846_x_at,1460590_s _at,1454378_at 18753 Prkcd 1442256_at,1422847_a_at 0.4 -0.1 0.4 0.1 0.1 12427 Ccna1 1449177_at 0.5 2.8 0.5 0.8 0.4 16773 Lama2 1426285_at -0.7 1.2 -0.1 -0.5 0.2 620772 Gm6180 #N/A 0000 0 215449 Rap1b 1455349_at,1435518_at,1435519_at 0.1 0.3 0.7 0.9 0.4 17931 Ppp1r12a 1437735_at,1437734_at,1453163_at, 0.1 0.2 0.4 0.3 0.8 1429487_at 19274 Ptprm 1422541_at -2.7 -1.4 -0.5 -0.3 -0.3 20511 Slc1a2 1451627_a_at,1433094_at 0.7 -0.2 3.6 4 2.9 18472 Pafah1b1 1417086_at,1427703_at,1448578_at, 0.6 0.1 0.1 0.2 0.8 1439656_at,1460199_a_at 15488 Hsd17b4 1417369_at,1455777_x_at 0 0 -0.2 -0.8 -1.3 211389 Suox 1451339_at 0.1 -0.4 -0.6 -0.5 0 13000 Csnk2a2 1429302_at,1453099_at,1460646_at 0 0.1 -0.1 -0.4 0.1 16149 Cd74 1425519_a_at 0.1 0 0.2 0.3 0.3 108147 Atic 1452811_at,1428506_at 0 0 -0.5 -1.4 -1.5 58875 Hibadh 1435967_s_at,1423780_at,1446297_a 0 0.3 0.1 0.1 0.3 t 630729 LOC630729 1421816_at -0.1 0.1 0.2 -0.9 -1.2

74167 Nudt9 1441633_at,1428164_at 2.9 3.2 2.5 2.8 2.8 238011 Enpp7 #N/A 0000 0 11686 Alox12b 1418266_at -0.2 0.1 0.1 0.2 -0.2 14712 Gnpat 1417456_at 0.1 0.1 -0.7 -1 -0.4 50780 Rgs3 1425296_a_at,1425701_a_at,1449516 0.5 0.2 0.2 4 1.3 _a_at,1454026_a_at 17165 Mapkapk5 1417016_at -0.1 -0.3 -0.2 -0.2 0.5 112406 Egln2 1416533_at -0.2 -0.2 -0.4 -0.4 -0.1 96979 Ptges2 1417591_at -0.2 -0.4 -0.4 -0.6 0.2 74091 Npl 1424265_at -0.2 -0.1 -0.2 -0.5 -1.9 14590 Ggh 1419595_a_at -0.1 -0.1 -0.2 -0.1 0 14598 Ggt1 1448485_at 0 0.3 -1 0.4 -0.3 163

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 18796 Plcb2 1452481_at 0 -0.4 -0.2 -0.4 -0.8 20768 Sephs2 1435602_at,1418325_at,1449040_a_a 0.1 -0.5 -1.2 -0.9 0.1 t 212398 Frat2 1455220_at -1.9 -1 -1.9 -1.1 -2.8 109652 Acy1 1419173_at 0.3 0.1 0.2 -2.2 -3.2 12651 Chkb 1448448_a_at 0.1 -0.4 -0.3 -0.6 -0.6 56362 Sult1b1 1418940_at -1.6 0.2 -0.8 1.2 1.5 18968 Pola1 1459319_at,1419397_at -0.2 0 0.3 -2 -1.9 15040 H2-T23 1449556_at 0 0.3 0.9 1.5 1.7 19062 Inpp5k 1456412_a_at,1416195_at,1438446_x 0.2 0.3 1 1.5 1.3 _at 19271 Ptprj 1455030_at,1427629_at,1425588_at, 0.9 0.5 0.8 1 0.1 1425587_a_at 66290 Atp6v1g1 1450926_at,1423256_a_at,1423255_a 0 -0.1 0 0 -0.4 t 13087 Cyp2a5 1422230_s_at 3.1 2.7 -0.1 -0.2 2.8 433759 Hdac1 1448246_at 0 0.4 0.8 1.2 0.2 102436 Lars2 1443672_at,1435682_at,1439225_at -0.1 -0.1 -0.4 -1.1 -0.2 14343 Fut1 1450359_at 0.5 0.4 0.5 0.1 0.3 547348 H2-T3-like 1452548_x_at 0.4 3.5 0.5 3.4 3.5 14451 Gas1 1456322_at,1416855_at,1448494_at 2.9 3.2 0.2 1.5 2.4 12583 Cdo1 1448842_at -0.4 -0.6 0.3 -1.2 0.3 67011 Mettl6 1432384_a_at,1419290_at 0.1 0 0.1 0.1 -0.1 269275 Acvr1c 1443225_at,1428032_at,1438309_at 3.5 3 1.9 5.5 2.3 14415 Gad1 1416562_at,1416561_at 0.2 -0.1 0.7 -0.3 0.3 74246 Gale 1424140_at -0.1 -0.4 -0.6 -0.9 -0.9 23821 Bace1 1455826_a_at,1421824_at,1421825_a -0.1 0.3 0 0 0.7 t,1450384_at 11855 Arhgap5 1423194_at,1457410_at,1450897_at, 2.7 2.2 2.4 0.6 2.3 1450896_at 15002 H2-Ob 1440837_at,1422201_at 0.1 0.2 -0.4 0 -0.5 22401 Zmat3 1449353_at -0.2 -0.4 -1.2 -2.9 -1.6 57254 Tas2r119 1450585_at -0.8 0.2 -2.2 -1 -0.7 232345 A2m 1434719_at 1 -0.7 2.1 1.1 1.4 16842 Lef1 1421299_a_at,1454734_at 2.7 1.5 2.8 1 2.7 58220 Pard6b 1423175_s_at,1423174_a_at 3.7 3.8 2.5 2 4.7 11548 Adra1b 1422183_a_at -0.1 0.2 -0.5 -2.8 -2.3 54123 Irf7 1417244_a_at 0.3 3.6 5.1 6 6.4 18584 Pde8a 1418407_at,1418406_at -0.1 -0.4 -0.6 -1.2 -0.2 55979 Agpat1 1421024_at,1421025_at 0 0.1 0 0.5 0 64436 Inpp5e 1423229_at,1423230_at 0.2 0 -0.4 -1 0.5 11298 Aanat 1421666_a_at 0.2 0.9 -0.3 2.4 0.4 667476 Gm13957 #N/A 0000 0 11797 Birc2 1418854_at 0.1 0.9 1.4 1.4 1 17907 Mylpf 1448371_at 0.3 0 0.1 0 0.2 164

Entrez ID Gene Name List of Affy ID 1hr_SLR 3hr_SLR 6hr_SLR 12hr_SLR 24hr_SLR 21873 Tjp2 1434600_at,1450984_at,1450985_a_a -0.1 0.2 -0.1 -0.6 -0.1 t,1434599_a_at 231691 Sds 1424744_at -0.1 2.9 0 1.6 2.3 18508 Pax6 1456342_at,1437816_at,1425960_s_a 0.9 1.5 1.5 2.3 2.2 t,1452526_a_at,1419271_at 231326 Aasdh 1440364_a_at,1419824_a_at 1.1 -0.2 -0.3 -0.8 -0.4 18806 Pld2 1457252_x_at,1417237_at 0.2 -0.1 0.2 0.1 -0.1 14985 H2-M10.1 1450587_at -1.2 0.1 0.4 1.1 0.3 16398 Itga2 1450501_at -2.7 0.4 -0.7 -0.5 -0.5 50935 St6galnac6 1423115_at 0 -0.1 -0.3 0.1 0.4 20355 Sema4f 1439768_x_at,1419328_at 0.8 1.4 1 1.7 4.7 545486 Tubb1 1444214_at 0.3 0.3 -0.2 0 0 103988 Gck 1419146_a_at,1425303_at 0.2 0.2 -0.4 0.3 0.9 14990 H2-M2 #N/A 0000 0 14389 Gab2 1420785_at -0.1 -0.2 0.1 -0.2 0.2 14960 H2-Aa 1452431_s_at,1438858_x_at,1435290 0.2 0.3 0.2 0.4 0.3 _x_at,1443783_x_at