Detecting Gene Modules Differentially Expressed in Multiple Human Brain

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THESIS

Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University

Zhiwei Ma

Graduate Program in Biophysics

The Ohio State University

2012

Master's Examination Committee:

Dr. Kun Huang, Advisor

Dr. Raghu Machiraju

Zhiwei Ma

2012

Abstract

Molecular screen methods such as microarrays have been used to identify molecular signatures and biological processes important for particular neuronal functions. This thesis applied a weight gene co-expression network analysis algorithm, edge-covering

Quasi-Clique Merger algorithm (eQCM), on human brain microarray data from the Allen

Institute of Brain Science. One thousand and sixty-six (1066) gene modules were identified. Within these 1066 gene modules, using eigengene as the representation of each gene module, 46 gene modules with significant p-values were selected by comparing the gene expression profiles between the hippocampus, parahippocampal gyrus and basal ganglia in the human brain. Through gene ontology enrichment analysis,

10 out of these 46 gene modules are significantly engaged in several biological processes of neuronal functions. The results showed that the correlation between molecular similarities and spatial proximity still exists in some human brain regions other than the neocortex.

Dedication

This document is dedicated to my parents.

iii

Acknowledgments

I would like to express my deep gratitude to my advisor, Dr. Kun Huang, for his excellent overall guidance during my stay at OSU. I would like to thank Dr. Raghu Machiraju for being my committee member and providing me many great revision suggestions for my thesis. I would like to thank Dr. Yang Xiang for instructing me about the usage of the eQCM program. I am grateful to Ms. Kim Leonard for editing my thesis.

Vita

2010...... B.S. Physics, Jilin University, China

2010 to present ...... Graduate Student, Biophysics Graduate

Program, The Ohio State University, USA

Fields of Study

Major Field: Biophysics

Table of Contents

Abstract ...... ii

Dedication ...... iii

Acknowledgments ...... iv

Vita ...... v

List of Tables ...... viii

List of Figures ...... ix

Chapter 1: Introduction ...... 1

1.1 Background ...... 1

1.2 Problem Statement ...... 2

1.3 Thesis Statement ...... 2

1.4 Roadmap...... 3

Chapter 2: Allen Brain Data ...... 5

2.1 The Allen Human Brain Atlas ...... 5

2.2 The Allen Developing Mouse Brain Atlas ...... 11

2.3 Human Brain Gene Expression Dataset Used in This Thesis ...... 18 vi

Chapter 3: Workflow and Algorithm ...... 20

3.1 Preliminary Data Processing ...... 21

3.2 Gene Co-expression Network Analysis Using the eQCM Algorithm ...... 21

Chapter 4: Differentially Expressed Gene Modules in Specific Brain Regions ...... 25

Chapter 5: Discussion & Conclusion...... 31

References ...... 34

Appendix A: Gene Symbols in Each of the Resulted 46 Gene Modules ...... 36

vii

List of Tables

Table 1. The donors’ information of these three datasets ...... 18

Table 2. Twenty-six gene modules significantly engaged in several important biological processes...... 27

viii

List of Figures

Figure 1. Enter gene name/symbol/NCBI Accession Number/Entrez Gene ID ...... 6

Figure 2. Gene search result...... 6

Figure 3. Planar view ...... 7

Figure 4. Correlation search ...... 8

Figure 5. The result of a correlation search ...... 8

Figure 6. Differential search ...... 9

Figure 7. The result of a differential search ...... 10

Figure 8. ISH data ...... 10

Figure 9. Enter gene symbol/ name/Entrez Gene ID ...... 11

Figure 10. Results of showing relevant search topics ...... 12

Figure 11. The relevant information of the gene symbol “Gabra1” ...... 13

Figure 12. Image series of “Gabra1” ...... 14

Figure 13. Neuroblast search ...... 15

Figure 14. Neuroblast search ...... 15

Figure 15. Results of a neuroblast search ...... 16

Figure 16. Anatomic search ...... 17

Figure 17. Temporal search ...... 17

Figure 18. Advanced search ...... 18

Figure 19. The summary flowchart of the procedures performed in Chapter 3 & 4 ...... 20

Figure 20. The pseudocode of the eQCM algorithm ...... 22

Figure 21. The histogram showing the number of elements of each gene module ...... 23

Figure 22. The spatial distribution of the samples ...... 26

Figure 23. The ANOVA boxplot for gene module #14 in three different brain regions .. 28

Figure 24. The ANOVA boxplot for gene module #30, #19, #20 and #2 in three different brain regions...... 29

Figure 25. The ANOVA boxplot for gene module #29, #34, #42 and #32 in three different brain regions ...... 30

Chapter 1: Introduction

1.1 Background

The human brain has a very complex structure. Particular neuronal functions are localized to different parts of the brain (Flourens, 1824; Broca, 1861). Brodmann’s work

(1909) of constructing a cytoarchitectural map of the neocortex showed distinct cellular organizations across different brain regions. Many previous research studies have been done to identify the functional specializations and related neuropathology in the brain.

Since the development of molecular biology, some molecular screen methods such as microarrays have been used to identify molecular signatures and pathways important for particular neurobiological processes. Previously, large-scale screenings for gene expression profiles across all different human brain regions were both costly and infeasible. Since the establishment of the Allen Institute for Brain Science, genome-wide atlases of gene expression in the brain of different species are being created (Jones,

Overly and Sunkin, 2009).

The genome-wide atlases of gene expression provide contemporary neuroscientists great opportunities to investigate gene expression patterns in multiple brain regions of different species and have led to knowledge discovery with respect to neurological disorders.

Using the data from the Allen Brain Atlas, French & Pavlidis (2011) showed that genes in connected mouse brain regions display similar expression patterns and identified genes correlated with autism spectrum disorder. Another study conducted by Zeng, Shen and

Hohmann et al. (2012) found gene expression variation between homologous human and mouse brain regions by using the in situ hybridization data from the Allen Brain Atlas.

The human brain in situ hybridization data, together with the mouse brain in situ hybridization data from the Allen Brain Atlas, served as a resource for the discovery of the correlation between molecular similarities and spatial proximity in the visual cortical regions of Rhesus monkeys (Bernard, Lubbers, Tanis et al., 2012). The research presented in this thesis also utilizes one of the Allen Brain datasets, specifically, the human brain microarray dataset.

1.2 Problem Statement

However, it is still unknown whether the relationship between molecular similarities and spatial proximity exists in the brain regions other than the neocortex. In addition, it is still unknown whether this relationship exists in the human brain. These questions will be pursued in this thesis. All these unknown problems have high implications for investigating the locality of molecular signatures correlated with several neurological disorders in particular brain regions.

1.3 Thesis Statement

Several approaches are available to study gene expression profiles through microarray data. One of these approaches, weighted gene co-expression network analysis, uses soft thresholding that converts the similarity matrix of gene co-expression measures to the

2 adjacency matrix of connection weights by using a sigmoid function or a power function with chosen parameters (Zhang and Horvath, 2005). Stephen Horvath’s group also developed methods to find consensus modules and create the concept of eigengene, which is biologically meaningful, to signify the expression profiles of each gene module

(Langfelder and Horvath, 2007). By using these theories as foundation, distinct gene modules correlated with autism were successfully identified (Voineagu, Wang and

Johnston et al., 2011), which showed that the weighted gene co-expression network analysis approach has high application value for searching molecular signatures for neurological disorders.

In this thesis, based on the methodologies of weight gene co-expression network analysis,

1066 gene modules were identified. Using eigengene as the representation of each gene module, I compared the gene expression patterns between the hippocampus, parahippocampal gyrus and basal ganglia in the human brain and selected 46 gene modules with significant p-values. Through gene ontology enrichment analysis, 10 out of these 46 gene modules are considerably engaged in the biological processes of neuronal functions. The results showed that the correlation between molecular similarities and spatial proximity still exists in some human brain regions other than the neocortex.

1.4 Roadmap

The roadmap of this thesis is stated as follows. In Chapter 2, two Allen Brain Atlases will be reviewed and the human brain microarray data used in this thesis will be described. In 3

Chapter 3, the human brain gene expression data processing steps will be presented. In

Chapter 4, the processes and results of identifying gene modules differentially expressed in multiple human brain regions will be described. In the last chapter, the results of this research work will be discussed and several possible future works will be given there.

Chapter 2: Allen Brain Data

The Allen Institute of Brain Science is constructing 3D mouse brain and human brain atlases which contain both anatomical and gene expression data. Currently, there are 10 sections available online: Mouse Brain, Developing Mouse Brain, Mouse Connectivity,

Mouse Spinal Cord, Mouse Diversity, Human Brain, Developing Human Brain, Non-

Human Primate, Glioblastoma and Sleep (http://www.brain-map.org). In order to provide readers a preliminary understanding of the usage of the Allen Brain Atlas, I will review two of these atlases in this chapter: the Human Brain Atlas and Developing Mouse Brain

Atlas. I will also describe the human microarray data used in this thesis, which has also been extracted from the Allen Brain Atlas.

2.1 The Allen Human Brain Atlas

The Human Brain Atlas is available through the following link: http://human.brain- map.org. On the top of the webpage, the user can choose to access the microarray data,

ISH data or MRI data. There is also a tab for downloading. Taking the microarray data as an instance, the user can click on the tab > Microarray. Next, the user can just browse the genes by picking up a gene category or by typing a specific gene name/symbol/NCBI

Accession Number/Entrez Gene ID of interest.

Figure 1. Enter gene name/symbol/NCBI Accession Number/Entrez Gene ID (http://human.brain-map.org)

In this section, a use case for one gene will be presented. For example, the user can type

"SEPT7" as shown in Figure 1. The webpage will display a heat map and relevant probes.

The user can click on the heat map to view the sampling brain structure, gene information and donor information.

Figure 2. Gene search result of “SEPT7”. The red arrow points to the tab for displaying the MRI data. (http://human.brain- map.org/microarray/search/show?exact_match=false&search_term=sept7&search_type=gene&page_num= 0&page_size=22&no_paging=false#show?exact_match=false&search_term=sept7&search_type=gene&_s uid=494) 6

The user can also click on the tab of “Planar View” to see the corresponding MRI data in a pop-out window.

Figure 3. Planar view (http://human.brain-map.org/mri_viewer?probes=1020524&donor=10021&well=9454)

The user can perform a correlation search by typing specific names of a brain structure as shown in Figure 4. For the example here, we type “Dentate Gyrus”. The website will display the results as shown in Figure 5.

Figure 4. Correlation search (http://human.brain- map.org/microarray/search/show?exact_match=false&search_term=sept7&search_type=gene&page_num= 0&page_size=22&no_paging=false#show?exact_match=false&search_term=sept7&search_type=gene&_s uid=494)

Figure 5. The result of a correlation search (http://human.brain- map.org/microarray/search/show?exact_match=false&search_term=sept7&search_type=gene&page_num= 0&page_size=22&no_paging=false#show?domain=12891&donors=9861%2C10021%2C12876&search_ty pe=correlation&search_term=&seed=1020524&_suid=913)

The user can perform a differential search by choosing the “Differential Search” selection and typing the target structure and contrast structure of interest as shown in Figure 6.

Figure 7 displays the result for this example case (target structure: the basal ganglia; contrast structure: the parahippocampal gyrus)

Figure 6. Differential search (http://human.brain- map.org/microarray/search/show?exact_match=false&search_term=sept7&search_type=gene&page_num= 0&page_size=22&no_paging=false#show?exact_match=false&search_term=sept7&search_type=gene&_s uid=494)

Figure 7. The result of a differential search (http://human.brain- map.org/microarray/search/show?exact_match=false&search_term=sept7&search_type=gene&page_num= 0&page_size=22&no_paging=false#show?domain1=4276%2C4242&domain2=4276&selected_donors=98 61%2C10021%2C12876&search_type=differential&page_num=0&_suid=917)

The user can also perform searches in the in situ hybridization data by selecting the “ISH

Data” tab as shown in Figure 8. Then the user can perform gene search, subcortex study, cortex study or schizophrenia study according to the user’s interest.

Figure 8. ISH data (http://human.brain-map.org/ish/search) 10

2.2 The Allen Developing Mouse Brain Atlas

The user can access the Developing Mouse Brain Atlas through the following link: http://developingmouse.brain-map.org. This website allows the user to browse the genes by picking up a gene category or typing a specific gene name/symbol/Entrez Gene ID of interest.

Figure 9. Enter gene symbol/ name/Entrez Gene ID (http://developingmouse.brain-map.org/)

In this section, a use case for one gene will be presented. For example, the user can type

"GABA-A" as shown in Figure 9. The webpage will return all relevant search topics.

Figure 10. Results of showing relevant search topics (http://developingmouse.brain-map.org/data/search/gene/index.html?term=GABA-A)

By clicking on the gene info shown in Figure 10, the webpage will display the gene symbol information, an expression summary histogram showing normalized expression across the structures over the different time points and corresponding image series.

Figure 11. The relevant information of the gene symbol “Gabra1” (http://developingmouse.brain-map.org/data/Gabrd.html?ispopup=true)

As shown in Figure 11, the user can view the thumbnails of the data at all the developmental stages including 3D tools, allowing the user to see the gene expression in the brain (see Figure 12).

Figure 12. Image series of “Gabra1” (http://developingmouse.brain-map.org/data/Gabrd.html?ispopup=true)

The user can also perform a neuroblast search by clicking on the plus sign (see Figure

13). The user can then select “neural plate” in the neuroblast box as shown in Figure 14.

The results will be displayed as depicted in Figure 15.

Figure 13. Neuroblast search (http://developingmouse.brain-map.org/data/search/gene/index.html?term=GABA-A)

Figure 14. Neuroblast search (http://developingmouse.brain-map.org/data/search/gene/index.html?term=GABA-A)

Figure 15. Results of a neuroblast search (http://developingmouse.brain- map.org/data/search/neuroblast/index.html?id=100074068&structure=neuralplate)

The user can also perform the following types of searches: anatomic, temporal and advanced as in Figures 16, 17 and 18, respectively.

Figure 16. Anatomic search (http://developingmouse.brain-map.org)

Figure 17. Temporal search (http://developingmouse.brain-map.org)

Figure 18. Advanced search. (http://developingmouse.brain-map.org)

These platforms provide us with an efficient search mechanism as well as an excellent source of visualization for the data.

2.3 Human Brain Gene Expression Dataset Used in This Thesis

There are three human brain microarray datasets available on the download page

(http://human.brain-map.org/static/download) of the Allen Human Brain Atlas:

H0351.2001, H0351.2002 and H0351.1009. The relevant information for these three datasets is listed in Table 1.

Donor Gender Age Ethnicity Post-mortem Interval H0351.2001 Male 24 yrs Black or African American 23h H0351.2002 Male 39 yrs Black or African American 10h H0351.1009 Male 57 yrs White or Caucasian 26h Table 1. The donors’ information of these three datasets

The gene expression dataset used in this thesis is H0351.2001. It was downloaded from http://human.brain-map.org/download/9861.zip, on January 13, 2012. The data were generated by using the Bioanalyzer Pico chip which were normalized prior to downloading. The detailed technical descriptions of generating this dataset can be found through the following link: http://help.brain- map.org/download/attachments/2818165/WholeBrainMicroarray_WhitePaper.pdf?versio n=1&modificationDate=1320108956444 (as of May 27, 2012).

This dataset contains 946 microarray samples (anatomical locations) for 58692 probes in one human brain.

Chapter 3: Workflow and Algorithm

The procedures performed in Chapter 3 & 4 can be summarized by the flowchart in

Figure 19. Human brain gene expression data processing steps will be described in this chapter.

Figure 19. The summary flowchart of the procedures performed in Chapter 3 & 4. Step 1 to 2 will be explained in Chapter 3. Step 3 to 5 will be explained in Chapter 4.

3.1 Preliminary Data Processing

The data processing steps in this section were performed by using MATLAB R2011a.

The data which have the status of non-RefSeq and the hypothetical genes and pseudogenes were removed first. The data with gene symbols of LOC653051,

LOC646470, LOC732327 and LOC731970 were also removed because these four entries were either withdrawn by NCBI, due to the insufficient evidence of defining a distinct locus (http://www.ncbi.nlm.nih.gov/gene/646470), or actually pseudogenes

(http://www.ncbi.nlm.nih.gov/gene?term=LOC732327, http://www.ncbi.nlm.nih.gov/gene?term=LOC731970), as of May 27, 2012. The means of all samples for each remaining probe were calculated and the data of the probes which have the largest mean for the corresponding gene have been retained respectively for further co-expression analysis.

3.2 Gene Co-expression Network Analysis Using the eQCM Algorithm

After the preliminary data processing, a total of 15532 unique genes were available.

Pearson’s correlation coefficient was calculated for each pair of genes. A revised version of QCM, the edge-covering Quasi-Clique Merger algorithm (eQCM), has been used here to build a weighted gene co-expression network and to identify different gene modules.

The user can refer to the following figure for the pseudocode of the eQCM algorithm.

Figure 20. The pseudocode of the eQCM algorithm (Cited directly from “Predicting glioblastoma prognosis networks using weighted gene co-expression network analysis on TCGA data”, by Xiang Y, Zhang C-Q and Huang K, BMC Bioinformatics, 13, S12, 2012, courtesy of Dr. Kun Huang).

The eQCM algorithm is a kind of greedy algorithm. Compared with the previous QCM algorithm (Ou and Zhang, 2007), the eQCM algorithm has a unique new search start condition of checking edge coverage and does not include the hierarchical construction that has no impact towards the resulting dense sub-networks (Xiang, Zhang and Huang,

2012). The input for this program was the matrix of Pearson’s correlation coefficients.

There were also several parameters for this program: γ, λ, t, β, C. The threshold in the pseudocode is computed by the following formula (Xiang, Zhang and Huang, 2012):

The density here is the ratio of the number of current edges over the maximum number of all possible edges of this weighted graph. The smaller the value of γ, the more gene

22 modules the user gets as well as an increase in the amount of noise. I chose γ=0.7, which was the default value of this parameter. For the parameter β, it controls the merging process of highly overlapped gene modules. To eliminate redundant information, the user can try a value of 0.999999. Here I chose β=0.9 to merge excessive sub-networks. For the parameter C, the value of 0 controls the program to use each edge weight (each matrix entry) as is in the program; the value of 1 controls the program to use the absolute value of each edge weight (each matrix entry) in the program. Here I chose C=0. For the other parameters, I chose λ=1 and t=1, which were both the default values.

As a consequence, 1066 gene modules have been identified by using the program. The number of elements in these modules ranges from 2 to 1976. Figure 21 shows the number of elements of each gene module.

Figure 21. The histogram showing the number of elements of each gene module. The horizontal axis is for the serial number of each gene module (from 1 to 1066). The vertical axis is for the number of elements in that gene module (ranging from 2 to 1976).

To represent the expression profiles of each gene module, the eigengenes for each of the modules were computed. This process is used to perform the singular value decomposition on the module expression matrix, M. Each row of this matrix contains the expression data of a gene in that module. The formula of the singular value decomposition is as follows:

M=USVT

The first column of V is the eigengene for that module (Langfelder and Horvath, 2007).

Chapter 4: Differentially Expressed Gene Modules in Specific Brain

Regions

In order to indentify gene modules differentially expressed in multiple human brain regions, representative gene modules with significant p-values should be selected for the first step. Due to the gene ontology enrichment analysis following, only the gene modules which have at least 10 elements can be retained, resulting in 862 modules. The data of specific samples of interest were extracted from the matrix of the eigengenes of every module. These samples of interest can be grouped into the following three categories:

Category 1: Samples from the hippocampal region (CA1, CA2, CA3, CA4, dentate gyrus, subiculum), 66 samples;

Category 2: Samples from the parahippocampal gyrus region, 15 samples;

Category 3: Samples from the basal ganglia region (putamen, globus pallidus, caudate nucleus), 57 samples.

According to the MRI data, the spatial distribution of these samples from these three categories can be demonstrated by the representation in Figure 22.

0 z

mni -10

-20 50 -30 0 -40 -50 -40 -20 0 20 -100 40 mni y mni x

Figure 22. The spatial distribution of these samples: red dots represent samples from the hippocampal region; green dots represent samples from the parahippocampal gyrus region; and blue dots represent samples from the basal ganglia region.

By using MATLAB R2011a, unbalanced one-way ANOVA was performed to calculate the p-values based on the three categories mentioned above. Only the gene modules with a p-value smaller than the ratio between 0.05 and the total number of gene modules were retained. After this process, there were still many overlaps in the remaining gene modules. To eliminate the overlap modules, these remaining sub-networks were merged iteratively by removing the modules which had an overlap larger than 50% with another module. The overlap ratio of module A and module B can be calculated as follows

(Xiang, Zhang and Huang, 2012):

The remaining modules can be considered as the representative gene modules. 46 modules remained. Please refer to the Appendix for the detailed information of the gene symbols in each of these 46 modules. I then used the ToppGene website

(http://toppgene.cchmc.org/enrichment.jsp, as of May 18, 2012) to perform gene ontology enrichment analysis with the Bonferroni correction. The results (Table 2) showed that 26 out of these 46 modules significantly engaged in several important biological processes. In addition, 10 out of these 26 modules directly regulate biological processes of neuronal functions.

p-value p-value Module generated by Biological Process generated # ontology by ANOVA enrichment 3 translational elongation 2.500E-16 1.057E-106 4 viral genome expression 5.282E-12 2.361E-28 37 nucleosome assembly 3.259E-10 3.031E-22 35 nucleosome assembly 3.938E-06 4.100E-22 9 regulation of immune system process 6.467E-18 2.092E-17 38 nucleosome assembly 2.123E-12 8.034E-14 1 cellular respiration 1.805E-15 4.775E-12 2 ensheathment of neurons 2.322E-27 4.757E-11 30 nitric oxide mediated signal transduction 1.240E-38 5.138E-07 29 neurotransmitter secretion 2.879E-36 6.928E-06 10 type I interferon-mediated signaling pathway 5.650E-26 2.574E-05 19 Neuron projection development 9.683E-11 7.421E-05 5 developmental growth 7.089E-42 1.771E-04 13 RNA processing 3.633E-05 1.347E-03 7 response to wounding 2.716E-42 1.606E-03 16 histone acetylation 1.381E-05 2.323E-03 34 regulation of neuron differentiation 1.866E-22 4.099E-03 27

45 actin filament capping 1.734E-26 9.365E-03 14 synaptic transmission 5.220E-09 1.593E-02 25 clathrin coat assembly 6.941E-16 1.806E-02 42 G-protein coupled receptor signaling pathway 6.587E-11 1.972E-02 20 neurofilament cytoskeleton organization 2.720E-12 2.188E-02 39 catecholamine metabolic process 6.496E-32 3.199E-02 32 regulation of epidermis development 3.426E-22 3.836E-02 15 positive regulation of smooth muscle cell proliferation 3.680E-26 4.154E-02 46 regulation of phagocytosis 3.576E-09 4.328E-02 Table 2. Twenty-six gene modules significantly engaged in several important biological processes. The highlighted rows of this table are the modules directly regulating biological processes of neuronal functions. The modules in this table and the modules listed in the Appendix use the same serial numbers.

The following figures are the corresponding boxplots of one-way ANOVA for the comparison of the three anatomical regions mentioned before. Each boxplot is for a distinct biological process of neuronal functions.

Figure 23. The ANOVA boxplot for gene module #14 for the biological process of synaptic transmission expressed in three different brain regions: 1, the hippocampus; 2, the parahippocampal gyrus; 3, the basal ganglia.

(a) (b)

Figure 24. The ANOVA boxplots for (a) gene module #30 for the biological process of nitric oxide mediated signal transduction; (b) gene module #19 for the biological process of neuron projection development; (c) gene module #20 for the biological process of neurofilament cytoskeleton organization; (d) gene module #2 for the biological process of ensheathment of neurons. These gene modules were expressed differentially in three different brain regions: 1, the hippocampus; 2, the parahippocampal gyrus; 3, the basal ganglia.

(a) (b)

Figure 25. The ANOVA boxplots for (a) gene module #29 for the biological process of neurotransmitter secretion; (b) gene module #34 for the biological process of regulation of neuron differentiation; (c) gene module #42 for the biological process of G-protein coupled receptor signaling pathway; (d) gene module #32 for the biological process of regulation of epidermis development. These gene modules were expressed differentially in three different brain regions: 1, the hippocampus; 2, the parahippocampal gyrus; 3, the basal ganglia.

Chapter 5: Discussion & Conclusion

In this thesis, I carried out a weighted gene co-expression network analysis on human brain microarray data and discovered 10 gene modules engaged in biological processes of neuronal functions. As shown in Figure 23, the expression pattern of the gene module

#14 is almost the same in the hippocampus and parahippocampal gyrus. However, in the basal ganglia, the expression profile is slightly different from the first two regions (the difference between the mean values of these regions is less than 0.001). Through gene ontology enrichment analysis, we know that this gene module is involved in the biological process of synaptic transmission. From Figure 24, we can see that the expression profiles of these four gene modules (#30, #19, #20 and #2) are expressed differently in those three brain regions (the differences between the mean values for those three regions are still less than 0.005). In addition, it is clear to notice that the expression profile differences between the hippocampus and parahippocampal gyrus are smaller than those between the hippocampus and basal ganglia. These four gene modules were found to be engaged in the biological processes of nitric oxide mediated signal transduction, neuron projection development, neurofilament cytoskeleton organization and ensheathment of neurons, respectively. As shown in Figure 25, the expression profiles of the gene module #29, #34, #42 and #32 in the basal ganglia have apparent differences from the profiles in the hippocampus and parahippocampal gyrus (the differences between the mean values for the hippocampus and basal ganglia are reaching or more than 0.005). And we can still notice that the expression profiles of the hippocampus and

31 parahippocampal gyrus are close to each other. These four gene modules were found to be involved in the biological processes of neurotransmitter secretion, regulation of neuron differentiation, G-protein coupled receptor signaling pathway and regulation of epidermis development, respectively.

From these results, we can clearly see the similarity of the expression profiles between the hippocampus and parahippocampal gyrus and the deviation of the expression profile of the basal ganglia from the first two regions. As I mentioned in the introduction part of this thesis, Bernard et al. (2012) identified the correlation between molecular similarities and spatial proximity in the visual cortical regions of Rhesus monkeys. My results demonstrated that this correlation still exists in some human brain regions other than the neocortex. In Bernard et al.’s work (2012), an explanation was offered that this correlation is due to the developmental origin of the cortical regions of their interest.

Based upon my result in this thesis and considering the difference of the neurodevelopmental origin of the basal ganglia from the other two regions, this explanation is still valid in this case for the brain region other than the neocortex. This, however, is subject to further cellular level investigations. In addition, my results identified the gene modules which regulate various neuronal functions. The disruption of the expression of these gene modules may be closely related to some neurological disorders. Further attention can be paid to the particular genes in this gene module in order to develop novel genetic therapeutic interventions. Some other future work can also

32 be done to compare gene co-expression patterns in some other functional cortical regions such as the motor cortex and somatosensory cortex.

To summarize the work of this thesis, based on the theories of weighted gene co- expression network analysis and the concept of module eigengenes, I utilized the eQCM algorithm to identify gene modules and selected 46 gene modules which were representative sub-networks with significant p-values of comparing the samples from the hippocampus, parahippocampal gyrus and basal ganglia. Through gene ontology enrichment analysis, 10 out of these 46 gene modules display significant involvement in several biological processes of neuronal functions. The results exhibited the continuing existence of the correlation between molecular similarities and spatial proximity in some human brain regions other than the neocortex.

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Appendix A: Gene Symbols in Each of the Resulted 46 Gene Modules

1 TBR1 MCHR1 DYDC2 GRHL2 IL13RA2 TRIM54

ATOH7 PTGER3 LOC100287347 ZNF831 BIRC3

RSPH9 HTR1A HS3ST2 C1orf135 NEUROD1

SLC2A6 HRH1 KCNB2 NEUROD6 LOC401097 MEIS3

EFCAB1 MUM1L1 VIPR1 KCTD16 RAP1GAP2 LPPR5

TNFAIP8L1 KCNV1 P2RX5 PRRG3 NT5DC3 FBXW9

PCDHAC2 ARNTL2 PABPC1L2A STYK1 C4orf44 CUL2

FAM19A1 C1QL3 MYH7 PPP1R14C PPP6R2 PITPNM2

SLITRK5 CDH9 C17orf68 KIAA1239 COL24A1 SLC1A6

KCNT2 ANKRD34A CENPW CDCA5 PTPRO BDNF

ACTA1 C11orf95 RAB27B CIDEC MKL1 TCERG1L

KLK7 KATNB1 FBXL18 PRPH2 KCNF1 CCKBR

NIPSNAP3A ANKRD33B NCRNA00205 RNF2 BAG4 LPPR3

NPY1R DACH2 JAG2 TMEM17 UBAP1 KIAA1715

PGBD5 NMT2 CLVS2 XRCC6BP1 FSD1 C16orf58

RNGTT ZNF554 FAM65B MED15 UNC5A FZR1

ZNF239 VTA1 DCP2 YARS2 SMPDL3A DHDH CUL3

RIPPLY2 HCCS SLC35A2 KCNIP4 KLHL18 LDB2

ZNF584 NPTXR PKIG EPHA5 ZFP64 CAPN1 GPR68

ASPHD2 UBE2QL1 CABYR DYRK2 RNF123

CHST1 HSPB3 C9orf40 TMEM155 CHAF1B

CCDC51 HECTD2 SIDT1 NUDT18 C1orf53 SSTR1

CNTN6 MVD C12orf73 UBE2Q1 NOVA2 KLHL7

CRYZ ZNF335 LOC402778 SUSD1 TMEM60 NLGN4X

RTN4IP1 ZFP1 AP1S1 CCDC103 RIMBP2 SLC16A14

ICAM5 C13orf1 CLSTN3 AP2A1 PPIP5K1

C1orf216 NR4A3 ATG5 SLC7A4 TSTA3 SRSF12

ZDHHC23 CPEB3 C12orf5 B4GALNT1 PCDH19

GDPD1 ASNA1 RPUSD3 MATK TIMM22 GRIN2B

TBC1D24 RAB36 GABRA5 NEURL1B NIP7 LPPR2

RSPO2 ECT2 PRICKLE2 KIAA0090 RAB40C DBNDD1

SRGAP3 PAPD7 TCEA2 PNCK PTPRR C15orf23

PCDH20 ARHGAP20 KIAA2022 NECAP1 C22orf39

RASL11B CD24 C1orf115 GRM1 MRPL4 CHRM1

MBLAC1 TUBA3C ST6GALNAC5 ALAS1 SMAP2

USPL1 GABRD RAB26 KIAA1468 MAST2 FBXO16

INPP4A RNMTL1 WDR41 RIC3 FAM25A TWF2 EPT1

FLAD1 HBQ1 NBAS AGBL4 RWDD2B GTF3C3

PSMG4 SEZ6L NANS TMEM188 FBXO28 HPCAL4

ADCK5 LCLAT1 PPFIA3 PRSS1 B3GAT3 KIF17

UBXN2B DBT RNF111 BAIAP3 TRIB3 AKR1C1

MAD2L1BP BHLHE22 PIM2 SHANK2 KCNIP2 SEMA4F

FAM123C TMEM198 FAM122A WHSC1 SHOC2 SPRN

DGKB GRIN3A KCNJ6 DDX51 FNIP2 VKORC1L1

CACNG3 CORO1A JAZF1 CSTF1 RAB22A DDX25 MCM6

FAM81A CTXN2 GLOD4 BYSL DMXL2 DCUN1D4

ZDHHC24 C1orf163 NOV PHF23 SORBS2 C12orf44

MAN1B1 GALNT9 MNAT1 NRBP1 RAB3C

IKBKG DMXL1 FAM103A1 TSGA14 NUDCD1

LOC377711 EID2B UGCG CDK16 FAM149A AHNAK2

COMMD9 LAMB1 LOC100129309 YOD1 CHD5 PHLPP2

CAMK1G PAK6 RPS6KA4 C16orf87 XK PRSS3 FAM32A

ZNF544 MORN4 CPNE4 HACE1 E2F3 SLITRK1

ARMCX5 CAMK2A ZNF821 AMN1 TRIM36 ADAM11

C6orf211 SLC35B1 EGLN2 SSX2IP ZNF540

AIMP2 BOD1 GRK6 C12orf47 EXOC4 RTF1 SLC25A46

BAP1 KIAA1012 PGM3 NPTX2 BTRC RALGAPB ZDHHC3

ASB6 EFNB3 LOC727967 ORC4L ABHD8 DPCD

RAB3GAP1 PDCD2L STK32C SLC39A14 LRFN2

DUSP14 SPIN2A USP5 C19orf30 MPND OGG1 PCDH8

GGA3 DGAT1 SEPT5 C2orf79 KLHL12 UHRF2

KIF21B GFRA2 DYNC1LI1 YIPF5 TRIM32 KCNG1

DLGAP1 TUBG2 RPF2 CCDC64 ZDBF2 C2orf69

KHDC1 HMGA1 LRRTM4 SPTLC1 ST20 C17orf76

NRSN2 PRKACA SEMA6B FNDC5 SYT17 MRPL36

PPP4R4 GPRIN1 KLHDC3 SYAP1 CSRNP2 AACS

ACCN1 GDA WDR74 RAB3A ACSL4 C1orf70

RAE1 EFCAB7 RAD23A ST3GAL3 LRRC14 TMUB2

GNG2 PPID SNAPC5 PREP SNX17 FLRT3 ATRNL1 MTX3

NAA30 GNB1L NPLOC4 GLRB TRUB1 MPP3

LRRC40 B4GALT2 MAP3K7 ABHD2 CNIH3 METAP1

CDC27 CECR6 R3HDM1 HMGN4 TSTD1

TBC1D7 LYSMD1 SLC4A7 FAM19A2 ADRM1 AAMP

ARFIP2 MFAP1 FNDC4 METTL11A GPR22 ZFAND2A

FITM2 ZNF207 MFSD3 RNF219 IKBKAP STEAP2

MFSD4 VAPB FAM73A RNF145 C7orf70 FLJ32790

ZNRF1 POLR3K WDR37 MARK4 AARS FBXO34

POLR2B FAM40A VPS25 PLEKHG5 ATP8A2 MED31

TMEM8B RIT2 C11orf87 VPS16 TBCC RASAL1 PPA2

PIH1D1 IQSEC1 EME1 HTR2A LRRC8B SUCLA2

NQO2 RNF139 WBSCR17 RFTN1 C11orf20 ARMC8

RAB39B TUBA1B LSM10 ZBTB11 B3GALNT1

TMEM199 CDC123 RNF41 TMEM22 DCAF4 MRTO4

PRDM2 SFXN3 ATRN FHL2 CBX6 ARMC9 DEDD2

SH3RF1 BCS1L SLC39A10 VPS41 RUVBL2 TBRG4

AKAP6 OTUB1 SLIT1 CNTNAP1 C7orf44 GPR26 NOL4

LARP4B CC2D1A EEA1 FAM110B ARMC10 RTN2 CTPS

PGP RELL2C9orf95 PSME3 PSMG3 USP7 TNPO2

KIAA1467 SGSM2 USP20 UBR1 ORC5L BTBD2

C1orf93 DNAJC9 RBM18 ACTN1 TRY6 MPPED1

C6orf115 ATXN7L3B SCP2 MPV17L2 TUFT1 SLC4A10

CHCHD4 GBA C1D HRNBP3 KIAA1045 F12 COASY

XKR4 RGMB PID1 OCRL RIMS4 TRPV2 BPGM TMEM177

DYRK1A HTR5A VPS26B NIPSNAP1 MANEAL

RAD17 MAPK10 GNPTAB B4GALT3 SBF1 SLC1A1

UNC80 RNF175 CYP4X1 RPUSD4 WDR54

MRPL39 TPST1 FAM50B ARHGEF9 PKD1 PCDHA3

LOC652826 MAPK14 OLFM3 FAM174A NELL1 UQCC

NUDT11 ZDHHC7 AKD1 CMC1 FAM102B FOXRED2

DOPEY1 TP53BP1 DGUOK ARMC6 MMS19

FAHD1 TXNDC9 TTC9 SERPINF1 BCKDK EXOC8

DNAJC30 C3orf17 ZNF25 SEC31A GOPC AARSD1

PPP1R12C COBRA1 CD200 TARS HSPA9 LOC100129272

NAPB CALML3 GFOD2 EEF1E1 FAM160A2 PANK2

ZNF131 NEURL4 WARS DUSP28 PFN2 TRAPPC1

ANKRD9 POLE3 FKBP1A C11orf74 EIF4E TMEM203

TTC19 CPSF4 LGALS8 PEX19 MANBAL EXT2 C1orf59

MTMR9 SEC23A CHMP1A RUSC1 USO1 GPR123

SNX14 GTDC1 PDXDC1 C12orf45 TM9SF2

HSPA13 ACTR6 TEX10 EHD3 APBA2 HSF2 HMGCS1

C6orf136 PMM1 SPIN2B ACTR1B MRAP2 AKIRIN2

MAP2K2 FAM174B SNX32 SNRNP25 COG8 EXTL1

NOMO1 SMS DDX41 PEX11B LSP1 MOAP1 SDHB

GUCY1B3 ARL16 CKAP5 SYT5 ARHGDIA UTP11L

PYCRL C6orf168 ASH2L RIMKLA RDH14

YJEFN3 FAM49A RFK SYN2 NCOA1 SLC25A11 NEU1

BRCC3 PPP3CC DPM1 FARSA PSMD13 NIF3L1

MRPL49 JAK3 TIMM50 PLEKHM3 NFS1 TMEM59L

C12orf52 AMPH TM7SF3 IPO5 C16orf93 YIPF1 FBXO44

NCALD TTC9C CNTNAP5 RFWD2 SAP130

DNAJC2 ZNF622 AGTPBP1 TUSC1 ELAVL4

UHMK1 CAMKV KCNC2 HSD11B1L RPRD1A

PRICKLE1 PCSK2 SSSCA1 B4GALT5 UBE2I NPRL3

LY6E HRAS SEH1L NRXN1 TTPAL BAG5 CADM3

BZW2 PRKCI DRG1 MSH2 OSTM1 C12orf23 SLBP PPP3R1

FAM165B AUH UNC13A PSMB3 SNUPN AP3B2

DCUN1D5 GNL3 KRTAP4-8 NUDCD3 PRRT1 CCNL2

DDX28 AHSA1 ADRA1B FAM3C SYNGR3

TTC39C TTLL12 UBE2T PAFAH1B2 SLC30A3 CHGA

SAMM50 CACNB3 COG1 IGSF8 PPP2R4 C10orf32 TBL2

TRAPPC2 YRDC HNRNPH2 CIAPIN1 FAM126B MOBKL3

SEC61A2 UBE2N SLC25A32 YME1L1 WDR45 LIN7B

TMEM191C AP1M1 ITFG1 KIF3B SPPL3 FAM160B1 SRPK1

NAA20 DUSP12 RAP1GDS1 ELOVL4 SH3GL1 MPI

REXO2 MYADM NLK C20orf7 CDK20 BAI3

DDX10 SNRPA1 DTNB SLC25A25 CELF3 MFSD5

HSPB11 DDX27 C7orf30 JKAMP USP22 SLC4A1AP

TRIM37 L3MBTL2 GPS1 DHX36 GMFB CELF6 NEURL

HCN1 MAP7D2 PDRG1 EIF6 STK25 STK24 NUDT9

C19orf62 C2orf80 RG9MTD1 EXOC6 FOXH1

TMEM55B PRKRA IFT57 PSMD2 NARF GAK SMARCA1

MAP1LC3A C16orf5 GPN1 C11orf68 UBE3A DOCK3

CYB5D2 GGT7 SEC61G ATP13A2 PPP2CA ZYG11B

C9orf16 UCHL5 GPD1L SC5DL PCYOX1L

MAST3 KHDRBS3 SRPRB SYP ITPA DNM1L

ARPC1A DENND1A HSD17B11 NGLY1 OXCT1

CITED1 CGREF1 VSTM2L HTT TRAPPC9 PHKG2

HDGFRP3 ARMCX2 RAB11A MAL2 AFTPH CHCHD1

LINGO2 GLT1D1 NUDT10 NDUFA9 OPCML SCAI

RABGEF1 NBL1 BCL11A PNMA2 FCHSD1 RBP4

SMYD3 ATP6V0E2 DCTPP1 WDR13 MRPL13

GPR155 MYRIP TMEM106B UBP1 BZRAP1 PSMB2

SNPH RAB11FIP5 LRRC68 GRINA LPPR4 BAI2 ERCC1

GFM2 AKR1B1 UBE2D3 BRWD1 UBFD1 TIMM23

SLC37A3 ZER1 PRPSAP1 POP4 LSM1 PDXP CDC34

FAM158A ATG9A ILF3 CCDC124 MRPL30 HPCAL1

PSMC3 COX4NB SSTR2 DDHD2 TSFM MRPL10 RPA2

TBPL1 MTCH1 NTRK3 ADCY1 SYT3 GGNBP2

KCNIP3 C2CD4C MTX2 FN3KRP KIAA0528 NDN

SURF2 DZIP3 PAIP1 MKKS FHOD3 GRIPAP1 C14orf129

CD83 VAPA IARS LRFN4 BID MEF2C NUP50

ANXA6 SRRM4 CASK C16orf91 MRPS10 GSTA4

TOMM40L SPHAR UBE2M TMEM55A EIF4A3

TBC1D9 CCDC3 UBR4 HSPC159 C9orf4 RANBP2

DHCR24 ABCF3 AP3M2 GOT2 KIAA0100 MRPL3

KCNQ2 TMCC1 UBE2D2 NTNG2 METTL5

RTCD1 GABBR2 APBB1 IMPA1 APBB3

THOC3 LRRC47 NIT2 BECN1 MRPS22 SCN9A

CAMKK1 NAT14 PCMT1 PRSS2 TRAK1 PPCS

PPM1A DUSP3 EID2 PARP2 FAIM2 TRAPPC4

RAB4A DNAJA3 FBXO33 SNX2 NAGPA ASB13

ZDHHC17 FLOT2 NPY GRIK2 FBXW5 CEP68 LARGE

ASTN1 C6orf154 LYRM4 C11orf41 BLCAP

DNAJB9 PDPK1 NCOA7 SS18L2 CRMP1 ITPKA

CACNA1B GSK3B NDFIP2 TOX4 NKRF BCAS2

C1orf230 CSE1L CACNB1 CHCHD6 DMRTC1 OSCP1

PLXNA1 ADARB1 LAMP2 PRKCE FAM190B GSS

MAGED2 REEP1 KALRN SCN3B ILF2 MAP6 PRKAR1B

SUMO3 MAPK11 MON1A PARP6 RUSC2

FAM49B EIF3I MMADHC SCN2A RAB24 C1orf31

C15orf61 MESP1 BSCL2 PRPF8 RUNDC3A NRIP3

CABP1 CSRP2BP ARF5 RFPL1S ECSIT SLU7 B3GALT6

CYP21A2 LRRC20 NCKAP1 ANKRD46 YTHDF2

TSG101 WDR1 BAI1 C11orf73 C3orf14 SATB1

RNASEN CYCS NANOS3 NECAB1 TMEM11 HK1

CRELD1 MAPK6 ARHGDIG DNAJB14 SRSF4 RPA3 SPIN1

LRRC24 SUPT7L TM2D1 NDUFAF1 ARMCX1

C12orf51 SYNGR1 PPP2R1A UBQLN1 THOC7 AP2S1

UBA1 NEUROD2 TXNDC17 FAM69B GDAP1 PPIL1

HERC1 GBF1 TECPR1 MADD GPRASP2 ATP6V1C1

FKBP1B WBP2 ITGB1BP1 LTA4H NUDT22 LMO4

C12orf10 CHRM3 LOC391358 PJA1 TUBB2C PIGZ

C19orf12 SRSF2 MDP1 CCT6A MAP2K1 EMX1 NAE1

PITPNB ACP1 DLG3 LEPROTL1 SNRPE PSMA5

GHITM HMGCR DISP2 ST6GALNAC6 KATNAL1

RSRC2 MLH1 EXOC1 CNOT7 PPP2R5B TCTEX1D2

KLHL9 CXorf40A GDAP1L1 TMEM70 SLC26A11

CAPZA1 CCDC24 RRP36 RANBP9 COPS4 GABBR1

C17orf108 C8orf46 EAPP FOXJ3 USP35 MUC5AC ACYP1

KPNA4 KRAS MAPK8IP2 TAF9 MRPS11 DLD EPRS

COPS3 RAB35 MRPL37 UBQLN2 DDX47

ARHGEF7 WDR82 KLHDC9 PSMA4 CNIH MAP9 MLF2

EFHD2 TTC7B SULT1A4 TDP2 DCAF11 TIPRL

MRPL15 SOBP TPM1 UBE2S SERF1A FAM173A

NDEL1 TYRO3 PWP1 MSRA POLR2K NAP1L2

TMEM126A ABCA3 ZMIZ2 SRGAP2 C11orf49 CALY

C7orf42 TMEM191A JOSD1 ACTR1A DDIT3 OAT ZBTB45

ACTR3 LOC642393 MRPL28 MAP4 PDK2 PTRH2 APEH

GABRB1 PPAPDC3 TSSC1 IGBP1 HPS6 MAT2B ZC3H15

GRSF1 NOP16 PPP2R3C HAGH KIAA1244 MRPL9

FDFT1 SLC25A12 TCEAL1 ARL4C HS6ST1 KIF2A

LYSMD2 SLC22A17 CHMP5 NELF CREG2 SLC8A2

IMP3 BSN BSG PDHB MAPK1IP1L MRPL45 ARF4 NISCH

TTBK1 LCMT1 KCNMA1 DPYSL4 ABHD14A

MAGEE1 CCDC28A PSMG1 CIAO1 PTS UBE2Z

KCMF1 CDK5 PTPRN2 CA11 ARPC5L SLC17A7

PRAF2 DTD1 CCDC153 SRPR MEAF6 C1orf212

MORF4L2 JAKMIP1 RARS ACAT2 NMNAT2 POLDIP2

SLC25A14 HARS KIF5A CCDC115 FIBP STAU2 NARS

ELMOD1 TUBB8 UBE2L3 CMAS HDHD2 PSMA7

ATP6V1B2 ACAD9 EFR3A RCN2 CCNDBP1 PRRT3

LY6H PCNP DNAJA1 FAM164A ICT1 SLC12A5 ATP2A2

ME3 MICAL2 C12orf53 PRPS1 SEPT3 PSMC6 NDUFB6

CNRIP1 ACTR3B BTBD1 GLRX TAGLN3 FDPS

SH3GL2 TMEM25 SPRYD3 ZRANB2 TAF6 PSMD14

COPS5 UGP2 DPF1 MRPS18C RNF208 TUBG1

MED10 FAM134B C9orf125 GGCT CA1 SNRPD1

SGSM3 SNRPB MRPL14 PLD3 SARNP SND1

SCCPDH AP2M1 RBX1 MGAT3 IAH1 RAD23B

UBE4A DLG2 MEA1 MBOAT7 CHPF2 TAF7 LOC650095

GNG3 PRUNE2 HOPX ATP5SL GPR162 MKL2 PAIP2

KPNA2 SACS PI4KA MRPL18 LASS6 FAM131A SLITRK4

PMPCB RAPGEF2 KIF3C LDOC1L SAE1 FAM58A

PFDN1 C20orf24 NCEH1 ARL6IP5 GMPR2

TMEM63C CCT8 CADPS SH2D5 PJA2 PDHA1

SLC25A22 ETS2 TOMM5 EPHA4 ACOT7 NRD1

BEGAIN CAP2 ATP5G1 LSM4 ACTR10 HNRNPK

PGM2L1 C16orf52 MRPS2 ACSL3 CDC42SE2 PSEN2

TOMM20 BLOC1S2 TUBA3D CRY2 FXYD6 SSRP1

FBXW7 MRPS35 FAM20B RAB6B MTMR4 CTSA

IDH3B PEX14 MPP1 MCTS1 MAP1A CDH18 HPRT1

OPTN RASGEF1A DEAF1 TPD52 NBEA ATP6V1G1 TMEM85

IFFO1 SERINC3 C3orf26 HTATSF1 ARL1 NHP2L1

LOC645225 TOP2B MRP63 PPP1R3F DBN1 BAT2L1

ATL1 CDKL5 ENTPD6 ZMAT2 STX12 CDK14 KLC1

C2CD2L ACOT8 TRO RBBP7 SEPT8 RHEB RAD21

BNIP3L UBXN6 NELL2 MDH2 LOC729164 VPS18

NOP10 TUSC2 ECHS1 LONP1 CACYBP

OCIAD2 GABARAPL1 CAMK2B SPG7 PSMA1 PKIA

NRCAM KIF3A PSMB5 C10orf35 SNCB BTBD9

GABRG2 PELI3 NICN1 GOT1 RHBDD2 NCRNA00116 PIN1

ARF1 AP3S1 PHYHIP MED27 TIMM17A KIAA0430

GLRX5 C19orf70 MNT GPC1 OCIAD1 TGOLN2

OTUD5 NRGN PSMD3 CCT3 NCDN MRPS25 ADAR

HMOX2 COPS6 TPM3 KIAA1797 TMEM160 CCDC6

FLOT1 UQCRC1 TBCD MRPS26 C1orf104 NRXN2

C20orf3 YPEL5 SUB1 KIF1A RASL10A PQLC1

MAGEF1 FAM134A IMMT EXOC7 NMT1 NRN1 PPP3CB

EIF3C DAP3 PA2G4 PNMA5 ATP5F1 SIRPA GALNT11

WDR7 SST NDUFV2 RBM8A C15orf24 KIAA1191

CPT1C RICH2 PDXK NAP1L5 SYT4 MRPS6 GPRASP1

FAM89B CCT5 ZNHIT3 CCDC85B AKAP11 ENO2

TSPYL2 OVCA2 RNASEK RTN1 NPTX1 PYGB GPX4

SLC25A4 UQCRC2 TXNL1 MRPS34 MAGEH1

TM2D3 PFKP LYNX1 GAP43 ATP6V0D1 DYNC1I1

TMEM14C COX7A2L UROD TSPYL4 RIC8A G3BP2 BLVRA

SARS F8A1 C22orf28 SYT13 SEC13 CCT7 LHFPL4 CELF4

MGRN1 LONRF2 SYBU DOK6 B3GNT1 GSTO1

GNAO1 DCTN2 VDAC3 YWHAZ TSPAN5 SNX3

CISD1 H2AFZ EPDR1 KCNMB4 PTDSS1 STUB1

WASF1 LDHA PLEKHB2 SNX10 PSMD7 PSMD1

CRYM GFOD1 FDX1L CLTA CX3CL1 C19orf60 PFKM

DNAJA4 TUBA1A IDS PPP1R9B TMEM111 YWHAH

SLC9A6 RASD1 KIF1B C16orf13 ZSCAN18 CAPNS1

TUBB4Q C5orf13 HN1 MAEA SERINC1 EEF1A2

RAB15 VPS35 LOC100131801 LINGO1 ARL8B

RNF112 LARP1 SCAMP5 NCRNA00086 MAP7D1

NME1 CBX7 STX1A MYCBP2 EFHA2 ATP1A1 GRB2

FBXO9 ZFAND5 COX5A MAFG ATP6AP2 SPINT2

TMEM208 C19orf10 PRDX2 NDUFB11 CCK C3orf39

VDAC1 PGAM1 ATP5B SVOP LAGE3 TMEM14B

CLSTN1 CAMLG PDE2A SAP18 SF3B5 ATP6V0B

IGSF21 PSMD8 B3GAT1 EBNA1BP2 FBXO41 TPI1

C14orf2 ARPC3 PITPNA CNTNAP2 PSMB7 DNM1

STOML1 ATP6V1H GNB1 THOP1 PSMC1 WSB2

NDUFA11 RPAIN MAP2K4 NSUN5 LOC150786

TSPYL1 SNCA TCP1 TXNL4A MTPN PSMB6 UBE2E3

FARSB KIFAP3 NT5C3L DCTN3 NDUFB3 DDX1

FBXL15 HSPA12A GSK3A TAX1BP1 PAFAH1B1

AP2A2 PSMA6 CHGB BTBD6 UQCRFS1 SERP2

CPNE6 LOC342541 STRAP SV2B SEC11C UBE2K

VDAC2 CHMP4B NCRNA00219 DIRAS1 HSPH1

ARF3 LDOC1 C16orf45 ATP5J2 NDUFAB1 CALM1

LOC387820 NUAK1 PTPLAD1 PDCD6 TCEB1 CCT2

RRAGA MRPL55 EVL RAN MEGF8 SPTAN1

NDFIP1 HMP19 DNM3 NDUFA5 CYFIP2 SCHIP1

MRPS21 COX7B ARHGEF4 ATP5A1 PPT1 PGK1

TMEM205 ENC1 CLASP2 TRAPPC5 PREPL PNMA1

TTC9B RTN4 DCLK1 ARPC2 ZFYVE27 RNF11

CALM3 PCSK1N ATCAY MAGED1 ATP1B3 CHP

SEZ6L2 CLIP3 NAPG POP7 PIP4K2B P4HTM MRPS24

SYT1 CDKN2D TERF2IP ATP6V1A CCDC56 TMSB10

PPP2R2B PNMAL1 SCG5 NDUFC2 DVL1 PCBP1 APLP2

LPHN1 GLS MYL12B ATP6AP1 SIN3B CCT4 CKMT1A

ASNS KIAA0513 LOC728327 NDUFC1 NEFL NPDC1

KIAA0284 BNIP3 ATP5J USP11 GPM6A TCEAL4 SHISA5

C11orf31 PGAM4 DYNC1H1 MORF4L1 TUBB3

OLFM1 TXN C14orf156 EDF1 NDUFV1 DUSP26

C3orf10 C17orf79 MGEA5 TCEAL5 LOC100128775

UBL5 TUBB ATP6V1F DSTN ABR TBCA NCRNA00087

FBXL16 MLLT11 ATP6V1G2 LOC100288117 SKP1

NDUFB4 PSMB4 CLTC PPIAL4B GPI UQCRHL

TMEM130 ATP9A EIF3K PARK7 NSF ISCU ATP5G2

LOC439953 ATP5H NDUFA8 FAM127A REEP5 BEX1 REEP2

FAM127B ALDOA VSNL1 DCTN1 SLC25A3

NDUFB8 C6orf1 ATP5G3 FAM166A UQCRH PRKCZ

GUK1 LOC401859 EIF4A2 COX4I1 MGST3 CHN1 THRA

COX6C BASP1 ANAPC11 XRCC6 THY1 YWHAB

CD99L2 ATPIF1 PACSIN1 TUBA1C DYNLL1

ATP6V0A1 NEDD8 USMG5 STMN3 COX8A ATP5L

HSPA8 DKK3 SRP14 SOD1 TUBA4A EIF3CL HINT1

NGFRAP1 CHCHD2 CALM2 NDRG4 YWHAG BEX2

STMN1 FAM128B PPIA MDH1 NDUFS5 SNAP25

STMN2 MIF TUBB2A NDUFA4 NME7 UCHL1 OAZ1

ATP6V0C PPIAL4G

2 CCNE2 C10orf128 DMBT1 C12orf32 BAZ1A

ABCA8 TSPAN8 CLCA4 MYOT CD22 SALL1

BRCA1 DEPDC7 TMC7 HOXD1 TP53TG5 IP6K3

GALNT6 DAAM2 RNF125 VRK2 TSPAN15 FRMD4B

LDLRAP1 SYT15 MYO1E MS4A15 NKX2-2 ITGA2

PRR5L KIAA1755 CCDC121 S1PR5 MYO1D TMEM38B

BEST1 NKX6-1 C21orf91 FYCO1 ENPP6 PLIN3 RAI14

SPATA6 MUC20 LRP2 DOCK5 CHRM5 DLL1

CDH19 SGK2 GAB1 TRIM56 ANXA4 SP110 AZGP1

CENPQ SHC4 PLCD1 PI16 TTC38 MITF TRPM6 HPN

CCNG1 PCSK6 MYOM1 CTNNA3 MEGF10

C10orf90 TMEM63A ST18 REST PBXIP1 RHBDL2

FRMD5 RFTN2 NIPA1 HS3ST5 NPHP3 ACTL6A

FZD5 SDS PPAP2C FAM38B LRRC1 OTUD7B PDK4

TRIM59 CUEDC1 PHLPP1 MAN2A1 OLIG2 GBP3

POC1B NOC3L SEMA4D C18orf56 SOX10

TMCC3 LITAF CHST14 RASGRP3 FBXO32 ERBB3

HSDL2 C19orf54 PLLP SH3TC2 C17orf85 DMRT2

PPFIBP2 NCAPD2 TMEM164 ITCH EMILIN2 IQGAP1

CERCAM MMP19 GM2A TTYH2 CHST3 C21orf62

C7orf61 ZFYVE16 BTBD16 SGK3 TENC1 FAM125B

DOCK1 SNX22 DMRTC2 RIT1 CNKSR3 LRRCC1

PGCP CHRAC1 NPC1 HSD11B1 ST6GALNAC3 RBP7

TMBIM1 LOC283999 NAIP PHF11 NIPAL4 MTUS1 WIPF1

KIF19 IFI44 BAZ2B ACSL1 PHLDB1 SEC14L5 RTKN

C1orf66 EGFL8 PDPR CDK18 SLC9A9 GRAMD3

GPSM2 STAG2 LPAR1 ANKRD13A DEPDC6

CNNM3 CD9 TMC6 CPM MYO9B OMA1 HN1L CREB5

AGXT2L2 TJAP1 TCFL5 ABTB2 ELOVL1 ACAA2

RAPGEF3 SHROOM4 DUSP16 CLDN11 ATG4C

CGNL1 NAGLU LDB3 RRBP1 LIMK2 PKP4 LRP10

SLC25A13 FOLH1B SPSB1 ARL13B ATF3 SERPINB6

ELOVL5 GNA13 UBA3 ICK CAT SGMS1 RELL1ISG20

TBC1D12 ATP11A KIF6 C14orf139 TMEM206 RIN2

PRRG1 CXCR4 TMEM209 IFT88 CDC42EP2 FBXL7

KCNH8 PHF8 TYMS KAT2B SYPL1 DERA PREX2

MID1IP1 PLEKHH1 CD97 FAM55C SCARB2 ACER3

SMOX SAR1B FOLH1 CDK6 CPNE2 PLEKHF1 NINJ2

PHF2 C11orf54 SEPT10 CEP350 HIP1 TFEB AP3B1 PADI2

PNPT1 PRTFDC1 DNM2 SLCO1A2 FNTB MAGT1 TPP1 IFIT2

PLCL1 ANLN STOM PLD1 TAP1 TRIP6 ZDHHC20 SFT2D1 DOHH

CLMN SERINC5 SHROOM1 SNX29 PICALM CREB3L2

DIP2B TMEM144 OPLAH NECAP2 FAM189A2 ARRDC2

GALNTL2 ACSBG1 NARG2 ENOSF1 ASPRV1

TRAK2 TP53TG1 HDAC1 ABCA2 ZCCHC24 NEK3

SFTPC KIAA0562 TMEM189 PIGK NEO1 ADI1 KIAA0776 DYSF

REEP3 PRR18 KRI1 ZFP36L2 TWF1 CD82 MUTYH ANGPTL2

CYP4V2 SNX1 SVIP KLK6 HHIP GPR137B AMPD3 LASS2

VAMP8 HAPLN2 JAM3 ATG3 PLEKHB1 SLC35A5 SNX6

PSEN1 TMEM123 SORBS3 KCNJ2 GAL3ST1 GLDN

MAPRE1 SMOC1 TSEN15 TMEM136 S100A16 HEG1

COL4A5 EFHD1 FGF1 ARHGEF37 FOXO1 SAP30 ASPA

VAMP3 CYP2J2 TMPRSS5 COL9A2 SLC13A3

NCKAP5 ANXA2 ZFP62 MOBKL2B ANKIB1 MTF1 RHOU

NEAT1 SLC45A3 AGPS ZKSCAN1 PAQR8 TMEM165

GPR37 MYO6 RFFL ITGA6 ADIPOR2 TCF12 S100A1 MSN GJB1

SPAG9 MAP4K5 THBS2 C15orf52 AHSA2

SLC12A2 BOK NEK9 ITFG3 PDZD8 APIP GNA12 POGK

IVNS1ABP KIAA0355 UNC5B FAM107B TMTC2 LBR

GLIPR2 DOCK10 UGT8 CHST6 P2RX7 C1orf144 BNIP2

IFNGR1 C11orf67 ERBB2IP RAB9A ECHDC1

EFNA1 SSH3 KCTD3 TJP1 C14orf147 KDSR ORMDL2

NCRNA00081 GCLC ATP6V0E1 CMTM5 GAB2 TJP2

MYL12A VEZF1 TMTC4 GALC MYO10 PAK2

KIAA1033 OPALIN PIK3C2B APOD NACC2 MTMR10

SLAIN1 MPST MOG LAS1L TMED10 FAM63A TTC32

GSTK1 CARNS1 NUDCD2 C12orf34 FNBP1

ANP32B PAIP2B PLOD3 NFE2L2 SYNJ2 MAP7

PTCD3 LAMB2 FGFR2 TSC22D4 PPP2R5A

KANK1 PPIL3 RBMS1 GLTP SPOCK3 CDR2L

PHGDH WASF2 SLC44A1 C6orf72 PECI TXNIP

MRPL48 GPR62 LMNA ITGAV FXR1 ADAMTS4 MAP4K4

CLIC4 SEPP1 LSM14A SNX5 ZCWPW1 RCC2 HSD17B4

CAPN3 MCAM HIGD1B CNTNAP4 FLJ10357

PDE4B HIST2H2AA4 SOX2OT MOCS1 HEPACAM CP110

PIR CLIP4 SH3PXD2A NET1 TMED2 MSH6 SEPT2 ANXA5

CTNNA1 H2AFJ PRDX4 KIF13B RNF114 IL6ST

ARHGEF10 BAMBI CYB5R2 SLC22A23 QKI HSPA2

CA14 WWC3 ITPKB TPPP3 ZNF664 SLC31A2 ZBED3

CFL2 EVI2A STXBP3 SEC11A KCNJ10 SDHC SEMA6A

RBM17 EPB41L3 SLC44A2 ADD3 TMEM98 MYLK

AMOTL2 N4BP2L2 MVP RNF130 TTC35 BDH2 HBS1L

FRYL APBB2 ENPP2 FAM82B FAM108B1 WNK1 LIPE SELS

ZNF385A NCOA4 MX1 CSRP1 ENPP4 BBX PTTG1IP

ZDHHC9 AK2 CBR1 SIRT2 PPAP2A SLC5A11 EFS NDE1

LEPROT LIPA BCAS1 DECR1 RBPJ SCD ABHD6

PPIF RNF141 MRPL19 MCM7 OMG MAN2B1 KIAA0494

CRYL1 CA2 BHLHE41 PON2 FKBP9 FBXO7

KIAA1598 CTDSP1 HADHB GPCPD1 YIF1A ERMN PSAT1

TROVE2 LSS PXK GPIHBP1 GJC2 ITGB1 FNTA C5orf4

SLC12A9 RHOQ FA2H PLA2G4C CHADL DENND5A CHD7

DYNC1I2 UBL3 ZBTB47 COL9A3 TST KTN1 C13orf15

VWA1 PTRF LZTS2 GATM TMEM87A RNF13 PIP4K2A CAPN2

USP54 METAP2 FAM123A SEMA4C SELK ENDOD1 DARS

PLEKHG3 TMEM125 WSB1 ARHGAP23 SPARC GSN

GOLGA7 DDX17 METRN SEPT4 PPP1R14A TMEM59

NKX6-2 NPC2 MBNL2 DLC1 SREBF1 CYTH1

DPYSL5 SOX8 SASH1 MAN2A2 DCI PMP2 PREX1

EDIL3 BRP44L DDR1 SPP1 NDRG1 CDKN1C OLIG1

SLC48A1 RASSF2 GCSH SEMA3B C11orf9 NIPAL3

CNDP1 B2M FEZ1 CDK2AP1 TALDO1 ANAPC5

SCRG1 LARP6 SYNGR2 C1orf198 RHOA GPRC5B

AIF1L S100B C6orf48 ZNF24 NENF AATK PMP22 RNASE1

BACE1 CD81 S100A13 DAZAP2 PCBP4 COMT CNTN2

PTP4A2 MAL CLDND1 CASC3 MAP6D1 MAG KIF1C

DBNDD2 QDPR MAT2A RNH1 C22orf9 CRYAB

LAMP1 LHPP PLP1 PLA2G16 LOC728914 HTRA1 GSTP1

PAQR6 EEF1A1 TF CNP PTGDS

3 FRA10AC1 DNAJC15 COMMD6 RPL22 LOC647030

NCRNA00275 ZNF525 ZCRB1 LOC100289349

HSBP1 C6orf48 EEF1B2 RPS15A C17orf89

LOC648771 ETFB RPLP0 NACA RPL39 NCRNA00188 RPL17 RPL7

PFDN5 EEF1G FLJ44635 UQCRB RPS16 RPL36AL

RPL30 RPS14 TPT1 RPS4X RPL27 RPL12 RPL36A RPS23 RPL37

RPL11 RPL29 RPL15 RPL24 RPL27A RPS7 RPS15 RPS24 RPS18 RPS11

RPS17 RPS13 RPL34 RPS27A RPL10A RPS20 RPL35A EIF1

RPL23 RPL32 RPS25 RPS21 RPS10 RPS19 RPL37A RPL26 RPL23A

LOC100291837 RPS27 RPL19 RPS29 EEF1A1 RPS12 RPL38 RPL31

RPS8 RPL21 RPS28 RPLP1

4 NOC3L TMX1 ZFP62 C6orf130 TDRD7 CYB5A

PRDX4 RPS27L SEC11A RBM17 ALG5 C17orf61

UXT SELS BRD7 RPL22L1 C19orf56 RPS5 FNTA PSME1

SSR4 ATOX1 RNF181 CLNS1A GLG1 METAP2 SELK

POLR2F RPS4Y1 RPS9 SEP15 TMEM59 C3orf1 POLR2I

POLR2G SEC13 NCRNA00275 C11orf10 DAD1 RPL10L

LOC100289349 FIS1 MRPL43 TMEM9B HSBP1

C6orf48 SEC11C BTF3 EEF1B2 DAZAP2 TBCB

RPL13A RPL10 RPS16 RPL5 RPS14 RPS4X RPL27 RPL11 RPL15

RPS7 RPL7A RPS11 RPS27A RPL10A EIF1 RPL37A

RPL19 TOMM7

5 ABCA1 IL33 GLI3 DIRAS3 SULT1C4 PON3 PAPLN

LOXL1 KCNN3 PBXIP1 FGF2 YAP1 BCL2 RFX2

GRAMD1C F3 NKAIN4 GPAM CYBRD1 SDC4 FXYD1

BBOX1 AQP4 HEPH BMPR1B SLC4A4 FAM189A2

NOTCH2 TMEM91 CYP4V2 LRP4 GJA1 S100A16

NTSR2 GPR125 MRVI1 MGST1 PPP1R3C

EDNRB SELENBP1 MYO10 CAMTA1 EFEMP1

PPAP2B ALDH4A1 ALDH6A1 SOX2 TRIL RAB34

AGXT2L1 PON2 METTL7A NTRK2 MLC1 FGFR3 MT1E

MT1G MT1X SLC1A3 SNTA1 AGT ATP1A2 APOE MT2A

TTYH1

6 ABCA1 STK33 SULT1C4 MYOM1 FGF2 YAP1 HSDL2

ZC3H12C GRAMD1C PITPNC1 FAT1 CYBRD1 GRAMD3

BBOX1 HEPH CGNL1 LRP10 GNA13 NINL CHDH

BMPR1B FAM189A2 NOTCH2 TIMP3 CYP4V2 EPHX2

DTNA NTSR2 GPR125 SSPN C15orf52 FBLN1 CNN3

MRVI1 BNIP2 ACSS1 CAMTA1 EFEMP1 NFE2L2

PPAP2B KANK1 CMTM6 SALL2 ITPKB SOX2 BDH2

H2AFV LEPROT TRIL RAB34 RAB13 ECHDC2

PON2 NFIA METTL7A MLC1 FGFR3 PMP2 AGT AHCYL1

7 EGFR PLA2G5 SV2C INHBB GRAMD1C F3 PITPNC1

FAM59B GPAM KCNJ14 SDC4 BBOX1 PLEKHO2 HEPH

TRPC3 CGNL1 PYGM S1PR1 SLC7A10 LFNG HIST4H4

BMPR1B SLC4A4 NOTCH2 TIMP3 HPR LRP4 CRABP1

JAM2 MRVI1 PPP1R3C MAPK4 ACSS1 CAMTA1

EFEMP1 PPAP2B RBMS1 NINJ1 HIGD1B ALDH4A1

LRIG1 RORA SOX2 ZNF385A TRIL RAB34 RHOQ METTL7A

FGFR3 PMP2 SLC1A3 SNTA1 AHCYL1 ATP1A2

ATP1B2 NDRG2

8 DAAM2 CTPS2 STK33 AASS PLIN3 GAB1 NEK7 ANKRD40

SUCLG2 RFTN2 OTUD7B SP1 ZNF621 GM2A

CHST3 FAT1 PELI2 GPSM2 UBXN2A KIF5B SHROOM4

SMC1A SERPINB6 ELOVL5 KAT2B HIP1 CHDH RDX

EPHX2 DTNA FGF1 RNF213 NCKAP5 C6orf204 TCF12

SRSF2IP BNIP2 FMNL2 ZBED1 PAK2 MACF1 KIF27

CCDC50 WASF2 MAP4K4 SNX5 WWC3 ZBED3

KCNJ10 FRYL H2AFV NAV2 RASSF4

9 SCIN CD68 EVI2B C1QC CLEC9A ITGAX LPAR6

PTPRC FYB MYO1F C1QA HAVCR2 P2RY13

LILRB4 WDFY4 ITGB2 INPP5D IFI30 HLA-DMB

FCGR3A CYBB RASAL3 SLC2A5 FCGR1A LST1

SUSD3 RHBDF2 HLA-DRA ALOX5AP P2RY12 LAT2

HMHA1 APBB1IP IL13RA1 VAMP8 ADAP2 HCST

HLA-DRB5 CMTM3 C1QB RNASET2 LGALS9C CX3CR1

C3 HLA-DPA1 HIST2H2AA4 AIF1 RGS10 TYROBP CSF1R CD74

10 ITGA1 APOL3 ADCY4 CHST14 TMEM88 ACVRL1

NOSTRIN C1orf64 LEF1 EGFL8 FGR IRF7 PLAT

FAM111A ITIH5 LRP10 TRIP6 DEGS2 TMEM204 TMEM123

HEG1 C15orf52 SLC2A1 GPER LAMB2 KANK1

GNG11 C1orf54 ID1 HIGD1B FOXC1 FLJ10357

VWF ICAM2 KLF2 ITPKB SLC44A2 ABCG2 IFITM2

CTDSP1 MCL1 IFITM3 IFITM1 CLEC3B IFI27 A2M

CLDN5 HLA-C

11 OTUD6A CXCL3 NKX3-1 C17orf106 KRTAP19-8

TMEM63B TMEM119 NOL6 PHF12 HOXB13 OR5L2 USF2

LRFN1 SLC9A3R2 C5orf58 ZNF157 ITGA5 ZBTB26

LCE1EC14orf177 SCGB1A1 CDKN2A KRTAP5-1 RHPN1

SLC22A18AS CEND1 HDGF FAM43B FAM19A5 CD79A

ODF3L2 KRTAP10-10 LOC100293090 LOC100131754

LOC100288418 LOC100288578

12 PHKA1 EGFR SULT1C4 ATP13A4 MRO ENKUR

SUCLG2 SDC2 ITPR2 YAP1 F3 PITPNC1 TLR4 TP53BP2

KIAA1407 FERMT2 S1PR1 PREX2 CHDH BMPR1B

ACSBG1 C21orf34 TIMP3 ITGB8 EPHX2 EZR NTSR2

PDLIM5 CNN3 PALLD MRVI1 BNIP2 EIF4EBP2

HMGN1 NTRK2 GLUD1

13 MED14 NBPF7 SP1 PHC3 TULP3 GCFC1

ANKFY1 LGTN ELK4 BTN2A2 ZNF532 SMC1A

CNTLN LOC100133280 PRPF38B LOC729915 DTNA RBM6

ZNF280D ACAP2 MTG1 TLK2 SRSF2IP ZNF292 KIF27

FTSJ3 SR140 STAG3L2 ZMYND11 POGZ RNPC3 FOXN2

HNRNPU NPIPL2 HMGN1

14 UHRF1BP1L DNAJC5 SRD5A1 ARFGEF2 STX1B

UBE2NL RFPL3S WDR47 NKIRAS1 GRPEL1

KRT222 MAPRE3 C1orf52 MYH10 MAPK9

TMOD2 MAP2 USP14 GARS UBE2V2 TPRG1L TMEM66

OLA1 TMEM189-UBE2V1 CAP2 SNAP91 NPTN ATP6V1E1

ATP6V1D TTC3 RAB2A

15 EGFR MTAP C12orf39 FAM69C ATP13A4 SUCLG2

RFTN2 ZNF621 PITPNC1 GPSM2 FLT1 SERPINB6

KAT2B VEGFA CHDH ACSBG1 NCKAP5 BNIP2

ZBED1 NACC2 MACF1 CCDC50 RBMS1

WASF2 MBD2 SNX5 GOLIM4 KCNJ10 LEPROT RHOQ

SASH1

16 IFT52 LDB1 ARFRP1 CPSF7 PHC3 PAPD4 FBXO18

ANKFY1 EP400 TCF3 USF2 HYOU1 OSBP IFT20 PMS2

C22orf30 MINK1 SAFB MSL1 RBM6 ARAP2 LRRC4B

ZSWIM6 SR140 STAG3L2 ZMYND11 RNPC3 NPIPL2

HMGN1

17 SEPT6 GNAS ELAVL2 BEAN EFR3A APOL2 MAST1

ABCG4 LIMK1 MAP3K9 PDE4A IQSEC3

TMEM229B RIMKLA DIRAS1 RAB37 CKMT1A

CKMT1B FGF9 SYT3 CNTNAP1 PELI3 REEP2 FCHSD1

PPAPDC3 SNAP25 STAU2

18 APOM CHST14 CYBRD1 C4A FAM111A LRP10 CXCR4

TRIP6 MXRA8 NECAP2 FAM189A2 SSPN MSN LAMB2

RARRES3 NUPR1 ITPKB BDH2 PTTG1IP RAB13

ZFP36L1 RHOC SPARC CD99

19 SYNGAP1 SYT7 CDK5R1 PDZD4 EPB49 ATXN7L3

PABPC1L2B AGAP2 DNAJC5 DLGAP1 FAM153A ADD2

RFPL3S SPTBN2 CAMK1 MAPRE3 MYH10

FAM153B JPH3 OLA1 CAP2 NCS1 NPTN TTC3

20 RET EPN3 AGPAT9 ESRRG SCN1B HAPLN4

RAB37 BEND6 ANK1 P2RX6 SHD FGF9 ASB13 APOL2

EFR3A MPP1 PVALB KCNC3 KCNC1 INA NEFH

GNAS

21 C11orf20 RIMS4 LMTK3 SNX32 FOXH1 MMP17

PCNXL2 TTBK1 CARM1 PRRT3 DUSP8

RNF208 NCS1 MAP3K10 PPP1R9B FBXO41 GP1BB

TRAF7 GRIN1 MEG3 LPHN1 JPH4

22 MICALL1 FOXO4 CCDC159 LOC100289550 ADAM15

SMARCC1 ANKFY1 LGTN NUMA1 PRKCSH ZNF532

USF2 LOC100133280 LOC729915 GALK2 RBM6 FTSJ3

C16orf88 NPIPL2 RUNDC2C

23 TNF XIRP1 LIF PIP5KL1 IL17RE SPEF2 HOXD9 ESM1

ZNF496 SAV1 DCAF8L2 GABRA4 LOC646960 HELB ALX3

MRGPRF MOGAT2 PSMD6 DUS1L

24 OSBPL6 STRBP SCN1A CDS1 MPP1 EFR3A

PDE4A RIMKLA FGF9 PELI3 FCHSD1 RELL2ABCG4

CD99L2 DIRAS1 INA SCP2 HAPLN4

25 ENPP5 HSPA4L BEND6 SRD5A1 ISCA1 SRPK2

CAB39 NKIRAS1 EPS15 GLRX2 MAPK9 TMOD2

GARS UBE2V2 OXR1 SULT4A1 SNAP91 MAP1B

26 CRCT1 PPBP GPR157 KRTAP5-10 KRTAP5-8 TREML1

DIRC1 FAM160B2 LENEP GLTPD2 ZNF646 EME2 NCR2

ELFN2 KRTAP1-3 ATP8B3 VSTM2B CGB5

27 ITIH4 HDAC7 LAS1L LOC653056 MUC20 WWC3

MUTYH TRABD UNK MBD6 TYK2 PILRB FBRS AZI1 DMPK

FUK DVL2

28 C21orf128 LY86AS SLC26A4 PKD2L1 FREM3

ANXA8 RHEBL1 OR14I1 NUDT4 HRH1 LOC646627

LOC401097 MAPK13 MUM1L1 CASQ1 FRMPD2

MEF2C

29 RIMS1 PCLO RBM9 SNAP91 STXBP1 DLGAP1 CDK14

GLS SLC4A10 PRKCE GPR22 GFOD1 SCN8A

STXBP5 SULT4A1 NAPB

30 HEYL TIMP3 NTSR2 C1orf54 SLC2A4RG RHOC MT1B MT1E

MT1G MT1X SNTA1 MT1H MT1A APOE MT2A TTYH1

31 LMBR1 ATPAF1 CMPK1 PDCD10 EXOC6B USP8

PDZD8 UBA3 GRINL1A C1orf58 NT5C2 UBE2G1

OSBP PL-5283 RAB7A

32 RXFP1 THEMIS KRT17 SATB2 TBR1 PART1

SLC26A4 LY86AS PKD2L1 LOC401097 ANXA8

HS3ST2 MPPED1 OVOL2

33 LUZP2 SNX7 MGST1 PNMT AMIGO2 EDNRB

AGXT2L1 NKAIN4 FNBP1L KAL1 ALDH2 C1orf61

GABRG1 CXCR7

34 RAPGEF4 ERC2 RFPL3S AK5 CAP2 DLGAP1 CHD5 NCS1

CDK5R1 LRFN5 FAM19A1 SLC4A10 KALRN

PRKCE

35 HIST1H2BD HIST1H2BJ HIST1H2BC HIST2H2BE HIST1H2BM

HIST1H2BI HIST3H2BB HIST1H2BN HIST1H2BO HIST1H2BH

HIST1H2BE HIST1H2BF HIST1H2BL

36 MYB WDR66 PPIL6 DNAH2 WDR86 C1orf194 YPEL1

LRRC56 B9D1 NNAT RSPH1 CORT C1orf230

37 HIST1H2BB HIST1H2AG HIST1H2BN HIST1H2BO HIST1H2BH

HIST1H2AD HIST1H2BE HIST1H2AH HIST1H2BF HIST1H2BL

HIST1H2AK HIST2H2AA4

38 H2AFB2 HIST1H2BB HIST1H2AI HIST1H2BO HIST1H2BH

HIST1H2BE HIST1H2BF HIST1H2BL HIST1H2AM HIST3H2A

ZNF625 HIST2H2AC

39 RSPH1 MAOB C9orf103 FNBP1L LRPAP1 RCN1

B9D1 PNMT AMIGO2 YPEL1 CXorf57

40 SLC26A10 LEPREL2 CHRD ZGLP1 KIAA0895L TNFRSF25

MAPKBP1 ABCC8 ATXN2L LOC728734 LOC100132247

41 H3F3A LOC728914 LOC644950 TROVE2 H3F3C H3F3B YBX1

C15orf21 DYNLT1 KIAA0467

42 SYTL5 TAC1 HTR2C KCNAB1 RGS14 HTR4 C14orf23

ANO3 PDYN ANKRD43

43 LOC100129616 BBS5 SOLH PILRB USP42 LOC100132247

LOC728734 ATAD3B MAPKBP1 CCDC57

44 TCP11L1 DNAJC6 SULT4A1 NAPB SNAP91 MAPK9

OXR1 UBE2V2 GLS STXBP5

45 DGCR9 ZNF238 DLGAP1 FAM153A SPTBN2 PCLO

RBM9 SPTBN4 FOXH1 FAM153B

46 C14orf23 TBC1D26 RGS14 HTR4 HPCA KCNAB1 ADRA2C

BCR SCARB1 SLC25A23