bioRxiv preprint doi: https://doi.org/10.1101/635243; this version posted February 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.
Sepsis-associated Pathways Segregate Cancer Groups Himanshu Tripathi+, Samanwoy Mukhopadhyay+, Saroj Kant Mohapatra*
+ These authors contributed equally to this work. * [email protected]
Abstract Background: Sepsis and cancer are both leading causes of death, and occurrence of any one, increases the likelihood of the other. While cancer patients are susceptible to sepsis, survivors of sepsis are also susceptible to develop certain cancers. This mutual dependence for susceptibility suggests shared biology between the two disease categories. Earlier analysis had revealed cancer- related pathway to be up-regulated in Septic Shock (SS), an advanced stage of sepsis. This has motivated a more comprehensive comparison of the transcriptomes of SS and cancer. Methods: Gene Set Enrichment Analysis was performed to detect the pathways enriched in SS and cancer. Thereafter, hierarchical clustering was applied to identify relative segregation of 17 cancer types in to two groups vis-a-vis SS. Biological significance of the selected pathways was explored by network analysis. Clinical significance of the pathways was tested by survival analysis. A robust classifier of cancer groups was developed based on machine learning. Results: A total of 66 pathways were observed to be enriched in both SS and cancer. However, clustering segregated cancer types into two categories based on the direction of transcriptomic change. In general, there was up-regulation in SS and one group of cancer (termed Sepsis-Like Cancers, or SLC), but not in other cancers. SLC group mainly consisted of malignancies of the gastrointestinal tract (head and neck, oesophagus, stomach, liver and biliary system) often associated with infection. Machine learning classifier successfully segregated the two cancer groups with high accuracy (> 98%). Additionally, pathway up-regulation was observed to be associated with survival in the SLC group of cancers. Conclusion: Transcriptome-based systems biology approach segregates cancer into two groups (SLC and CA) based on similarity with SS. Host response to infection plays a key role in pathogenesis of SS and SLC. However, we hypothesize that some component of the host response is protective in both SS and SLC. Keywords: Sepsis, Septic shock, Cancer, KEGG Pathway, TCGA, GEO Background Sepsis is a potentially life-threatening complication caused by dysregulated host response to infection, often leading to organ failure and death. Estimated global burden of sepsis is more than 48.9 million people in 2017 with 11 million deaths [1]. Septic shock is the advanced stage of sepsis with metabolic dysregulation and uncontrolled hypotension. Several epidemiological studies have linked sepsis and cancer [2, 3]. Liu et al. [2] conducted an association study between sepsis and ensuing risk of cancer in elderly adult population of the United States, and observed that sepsis is significantly associated with increased risk for many cancers including chronic myeloid leukemia, myelodysplastic syndrome, acute myeloid leukemia, cancers of the cervix, liver, lung, rectum, colon. Another association study revealed 2.5 fold increased risk of sepsis in survivors of cancer in
1 bioRxiv preprint doi: https://doi.org/10.1101/635243; this version posted February 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. community-dwelling adults (the risk is increased up to 10 times in hospitalized cancer patients) [3]. Co-occurrence of cancer with sepsis is associated with higher mortality than sepsis alone without cancer [4]. On the other hand, sepsis is a common cause of death in critically ill patients with cancer, with high ICU and hospital mortality [5–7]. Interestingly, mortality due to sepsis varies widely from 42 to 82% across cancer tissue types [8], suggesting varying likelihood of survival of patients suffering from different cancers. This study is motivated by multiple shared features of septic shock (SS) and cancer. There is co-occurrence of the two entities, with synergistic effect on mortality. Both are associated with inflammation at some stage of the disease. Inflammation is well understood to promote malignant growth with participation of diverse immune cells and molecules, such as, cytokines [9]. Similarly, sepsis is understood as a non-resolving inflammatory response to infection that leads to organ dysfunction [10]. Both the diseases are associated with anaerobic metabolism with lactic acidosis being a hallmark of septic shock [9, 11]. In our earlier work, we have observed a cancer associated pathway to be significantly up-regulated in septic shock [12]. Additionally, there are previous reports on shared molecular changes in sepsis and cancer. Bergenfelz et al. [13] reported that Wnt5a induces immunosuppressive phenotype of macrophages in sepsis and breast cancer patients. HMGB1, a key late inflammatory mediator of systemic inflammatory response syndrome associated with bacterial sepsis, is also implicated in tumorigenesis and disease progression [14]. Muscle wasting - observed in patients with cancer, severe injury and sepsis - is associated with increased expression of several genes, particularly transcription factors and nuclear cofactors, regulating different proteolytic pathways [15]. Methodologically, all of these studies employed gene-level analysis, i.e., considering gene as the functional unit. On the other hand, a gene set or pathway represents coordinated molecular activity and represents a higher-order functional unit in a tissue or cell. Pathway-level analysis allows detection of a cumulative signal that is not accessible at the gene-level. To our knowledge, there is no report in literature on pathway-level comparison between sepsis and cancer. In the present study, we have performed unbiased analysis of SS and cancer datasets to discover shared patterns of pathway-level transcriptional alteration underlying the two illnesses. Methods Gene expression data TCGA data: Gene expression data as FPKM (Fragments Per Kilobase of transcript per Million mapped reads) values were retrieved from The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/) on July 5, 2018 for 17 different human cancers i.e., bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), thyroid carcinoma (THCA) and uterine corpus endometrial carcinoma (UCEC). For each cancer type, TCGA project code was provided in the search field and RNA-seq data for paired samples (each pair consisting of tissue from tumour zone and tissue from adjacent unaffected zone in the same individual) were downloaded. In all, gene expression data were derived from 687 patients with cancer. Data were transformed to logarithmic scale (base 2). GEO data: Six studies of septic shock (SS) were selected following the procedure described earlier [12]. Normalized gene expression data from the series matrix files were retrieved from NCBI Gene
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Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) on April 10, 2019. Data were transformed to logarithmic scale (base 2). Expression intensity for each Entrez gene ID was calculated after removing duplicated probe sets. Genes common to all SS studies were included in the analysis. In all, gene expression data were derived from 445 patients with SS and 116 control subjects. Redundant samples (other than control and SS) were excluded from analysis. Characteristics of 23 distinct data sets used in the current study (6 of SS and 17 of cancer) are listed in Table 1. Each data set consisted of transcriptome-wide expression data from a number of patients suffering from a single disease (SS or cancer). For SS, each data set consisted of blood transcriptome data. For cancer, each data set consisted of transcriptome data from a tissue. Control was defined as adjacent normal tissue for cancer (TCGA), and a healthy subject for SS (GEO).
Table 1: Characteristics (such as tissue of origin, source database, disease type, sample size of each study and details about the platform technology used to generate the data) of the 23 data sets (17 cancer + 6 septic shock) included in the analysis. Study_code refers to the code assigned by the source database (either TCGA or GEO) to the data set. TCGA stands for The Cancer Genome Atlas. GEO stands for NCBI Gene Expression Omnibus. Paired control refers to adjacent normal tissue in the same cancer patient. Technology for transcriptome assay is either sequencing (RNA-seq) or hybridization-based microarray (Affymetrix).
Number Study_C Paired Data source Disease Tissue of Technology ode control samples
BLCA TCGA Cancer Bladder 38 Yes RNA-seq (Illumina)
BRCA TCGA Cancer Breast 220 Yes RNA-seq (Illumina)
CHOL TCGA Cancer Gallbladder, liver and parts of biliary tract 18 Yes RNA-seq (Illumina)
COAD TCGA Cancer Colon and rectosigmoid junction 82 Yes RNA-seq (Illumina)
ESCA TCGA Cancer Esophagus 16 Yes RNA-seq (Illumina)
Base of tongue, floor of mouth, gum, hypo- HNSC TCGA Cancer 86 Yes RNA-seq (Illumina) and oro-pharynx, larynx, etc.
KICH TCGA Cancer Kidney 48 Yes RNA-seq (Illumina)
KIRC TCGA Cancer Kidney 144 Yes RNA-seq (Illumina)
KIRP TCGA Cancer Kidney 64 Yes RNA-seq (Illumina)
LIHC TCGA Cancer Liver and intrahepatic bile ducts 100 Yes RNA-seq (Illumina)
LUAD TCGA Cancer Bronchus and lung 114 Yes RNA-seq (Illumina)
LUSC TCGA Cancer Bronchus and lung 98 Yes RNA-seq (Illumina)
PRAD TCGA Cancer Prostate gland 104 Yes RNA-seq (Illumina)
READ TCGA Cancer Rectum rectosigmoid junction 20 Yes RNA-seq (Illumina)
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STAD TCGA Cancer Stomach 62 Yes RNA-seq (Illumina)
THCA TCGA Cancer Thyroid gland 116 Yes RNA-seq (Illumina)
UCEC TCGA Cancer Corpus uteri 46 Yes RNA-seq (Illumina)
Septic Microarray (Affymetrix GSE4607 GEO Whole Blood 84 No Shock HGU 133 Plus 2.0)
Septic Microarray (Affymetrix GSE8121 GEO Whole Blood 75 No Shock HGU 133 Plus 2.0)
Septic Microarray (Affymetrix GSE9692 GEO Whole Blood 45 No Shock HGU 133 Plus 2.0)
GSE1390 Septic Microarray (Affymetrix GEO Whole Blood 124 No 4 Shock HGU 133 Plus 2.0)
GSE2637 Septic Microarray (Affymetrix GEO Whole Blood 103 No 8 Shock HGU 133 Plus 2.0)
GSE2644 Septic Microarray (Affymetrix GEO Whole Blood 130 No 0 Shock HGU 133 Plus 2.0)
Pathway Enrichment Analysis Pathway (gene set) enrichment analysis was performed using the algorithm previously described [12, 16]. Gene sets were defined based on pathways annotated at KEGG [17]. Any pathway with small number (10 or less) of genes was discarded from analysis. For each gene, t- statistic was computed to denote change in gene expression in case group compared to the control group. For each pathway, a score was calculated by weighted averaging (i.e., sum of the gene-level t-statistics divided by the square root of the number of genes in the pathway) of all gene-level t- statistic for the pathway. Significance of the observed pathway score was calculated by permutation testing performed in the following manner. In each permutation, the samples were randomly re- labelled as case and control, with calculation of a simulated pathway score. This was done 10000 times generating 10000 simulated values representing the null distribution of the pathway score. Deviation of the observed pathway score from the null distribution was quantified by the fraction of times that the simulated score was more extreme than the observed score. This result was assigned as permutation p-value of the observed pathway score. Pathway enrichment analysis was performed using code modified from the R function gseattperm() of the package Category [18]. Cluster Analysis Pathway scores of all 23 studies (6 SS + 17 cancer) were subjected to hierarchical clustering in the following manner. First, the Euclidean distance matrix was computed to capture the pair-wise dissimilarity among the studies. Thereafter, the distance matrix was subjected to agglomerative hierarchical cluster analysis, with “complete” linkage method. Distance matrix computation and cluster analysis were performed using the R functions dist() and hclust() respectively. Output of the cluster analysis was plotted as a dendrogram. Visualization of Pathway-level and Gene-level Expression Scores A pathway was selected if it was significantly enriched (permutation p < 0.01) in 80% or more of the studies in one or both of the cancer groups (SLC, CA). Pathway score matrix was generated for all selected pathways across all 23 data sets. Heat map was generated with the R function heatmap.2() of the package gplots [19]. For each pathway, mean pathway score across the disease group was calculated separately. Boxplot of the pathway scores for the three disease groups
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(SS, SLC and CA) was drawn using R function boxplot(). For generating gene-level heat map of individual pathway, the following steps were followed. First, average log-expression level was calculated for case group and control group separately. Log2(fold -change) or LFC was calculated by subtracting the average control value from the average case value. This was done for each gene. For each disease type (SS, SLC or CA), median LFC was calculated across the studies in that disease group. Combined heat map was generated based on the pathway genes and the three disease groups. Only those genes with similar LFC directionality in SLC and SS were included in visualization. Network analysis Firstly, a background network was constructed by including all the pathways (KEGG) [17] with overlapping gene memberships, i.e., for a pathway to be included, it must share at least 5% of the total number of genes with another pathway. Pathways connected to less than 3 other pathways each were dropped from network analysis. In this network, each pathway was considered a node, and the edge between two nodes represented overlap between the two pathways. In this way, a network was constructed with 244 nodes and 5304 edges. Degree distribution of the network was calculated using the function degree_distribution() of the package igraph [20]. Plot of the degree distribution of the network was drawn. For each node in the network, degree and betweenness centrality were calculated with the R functions degree() and betweenness() respectively. In the network diagram, selected pathways were shown as nodes coloured in red. Box plot was drawn to show the difference of degrees between selected set and other pathways. Sample-level pathway score Individual pathway scores for the cancer patients were computed in the following manner. For each subject, two genome-wide expression vectors were retrieved from TCGA: one for the tumour tissue (T) and another for the adjacent normal tissue (N). Normalized gene expression vector (E) was then calculated by subtracting the normal expression values from the tumour expression values (E = T - N). For each of the selected 66 pathways, a score (Z) was calculated as the weighted average of the expression of the genes in the pathway (i.e., sum of the individual gene expression scores divided by the square root of the number of genes in the pathway). This resulted in 66 pathway scores for each patient. These individual pathway scores were used for survival analysis.
Machine learning For the machine learning-based prediction, we retrieved additional transcriptome data for SLC and CA cancers from NCBI GEO. Six datasets containing 542 cancer subjects (of both SLC and CA) and 180 healthy control subjects were included (Additional File 7: Table S4.). The additional validation data sets were required because the TCGA data sets were used for feature selection (i.e., 66 pathways) and segregation of cancer groups (SLC and CA). For each cancer sample, pathway scores were generated by weighted averaging of the gene-level t-statistic between the case group and control group, (i.e., sum of the individual t-statistic divided by the square root of the number of genes in the pathway). The scores of the sixty-six pathways were used as input and the cancer group label (SLC or CA) as output in machine learning-based classification of cancer patients. Support vector machine (SVM) and neural net (NN) classifiers were implemented using R package MLInterfaces [21]. SVM was used through function call Mlearn() with learning function svmI. Neural Network was used through function call MLearn() with learning function nnetI and three nodes in the hidden layer, with weight decay set to 0.01. Confusion matrix from the classifier output of five-fold cross-validation was collected for calculation of misclassification rate (fraction of samples wrongly predicted by the algorithm) and accuracy.
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Survival Analysis Based on the number of cases and available survival information, three SLC cancer types (HNSC, KIRC and LIHC) were selected for survival analysis. The following clinical metadata were collected as provided by TCGA: days (to death or last follow-up) and outcome (survivor or non- survivor). Patient-level (sample-level) pathway score was used for analysis. For each cancer type, the patients were divided into two groups (high-score and low-score) by applying the median pathway score as threshold. Survival plots were generated using the functions in the R package survival [22] as described here. First, a survival object was created applying the function Surv(), with day and outcome. The output, i.e., the fitted model, was passed to the function survfit() that created two survival curves, based on the level of pathway score (high or low). Survival plots were displayed using the function ggsurvplot() from the package survminer [23]. Significance of the difference between the survival plots of the two curves was calculated by the function surv_pvalue() from the same package.
Code and data availability All programming was done in the R programming language [24]. Data and R code are available at the following link: https://figshare.com/ (https://doi.org/10.6084/m9.figshare.8118413.v3, https://doi.org/10.6084/m9.figshare.8118647.v5). The whole data can be downloaded as a single zip file (tcnibmgdoc.zip). Upon uncompressing the zip, instructions for running the code and generating the figures of this manuscript are available in the file howto.pdf. Selection of the transcriptome data sets and analysis workflow leading to the final list of 66 significant pathways are described in Fig. 1. The study characteristics of the data sets are listed in Table 1.
Fig. 1: Selection of data and analysis workflow. Left-most column shows the source of data from GEO for SS and TCGA for cancer. Data for SS were applied first followed by data from TCGA. Next column describes the processing of the data that form a progressive filter for narrowing down the number of pathways of relevance. KEGG contains 272 pathways of which 90 were assigned significant pathway score by Gene Set Enrichment Analysis (details in the main text). The right-most column lists the interpretations
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Results The transcriptomic data for 23 studies (17 cancer and 6 SS) consisted of 687 patients with cancer and 445 with SS. The data were subjected to progressive analysis and pathway filtering (Fig. 1). Hierarchical clustering revealed two groups of cancers At the outset, independent of our data, there were a total of 272 pathways in the KEGG database. Application of permutation-based testing of each pathway, revealed that 90 of these were significantly (p < 0.01) enriched in each of the 6 SS data sets, thus constituting a robust set of SS- specific pathways. Hierarchical clustering on combined cancer and sepsis data sets for these 90 pathways revealed two groups of cancers, with one group segregating with SS (Additional File 1: Figure S1). The 6 cancers (HNSC, ESCA, STAD, LIHC, CHOL, KIRC) belonging to the SS clade were termed Sepsis-Like Cancer (SLC). The other 11 cancers (BLCA, BRCA, COAD, KICH, KIRP, LUAD, LUSC, PRAD, READ, THCA and UCEC) formed the other clade and were termed the CA (Cancer Alone) group. In order to exclude those pathways that may be irrelevant to cancer biology, the 90 pathways were tested for enrichment in any or both of the cancer groups (i.e., significantly enriched in at least 80% of a group of cancer). 24 out of the 90 SS-specific pathways were observed not to be associated with any of the two cancer groups. Exclusion of these 24 non-significant pathways resulted in retention of 66 pathways significantly associated with both SS and cancer. Pathway score matrix of these 66 pathways across all diseases (including SS, SLC, CA) was visualized as a heat map (Fig. 2A). The sample dendrogram of this heat map recapitulated the segregation of the cancer groups as observed earlier with 90 pathways (Additional File 1: Figure S1). In general, the heat map demonstrated up-regulation of the pathways in SS and SLC. Further, for each pathway, mean score was calculated across all data sets in one disease group (SS, SLC or CA). Box plot of these scores clearly demonstrated the shared directionality in pathway dysregulation in SS and SLC, i.e., in both these conditions there was up-regulation of the pathway (Fig. 2B). Additionally, the average number of pathways up-regulated in a disease group was observed to be 63, 58 and 11 for SS, SLC and CA respectively (Additional File 4: Table S1), thus establishing general agreement in the direction of pathway transcriptional change between SS and SLC. The overall trend in pathway dysregulation was also reflected in the gene-level heat map for individual pathways (Additional File 2: Figure S2).
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Fig. 2: (A) Pathway heat map for 66 selected KEGG pathways where each pathway is significantly perturbed in at least 80% of the studies in one or both of the two groups of cancers. Colour of the cell is explained by the colour key histogram provided on the top left. Green indicated down-regulation of pathway, red indicates up-regulation. In the column-sidebar, purple indicates SS group, cyan indicates SLC group and blue indicates CA group. Positive pathway score is presented in red, negative pathway score in green. (B) Box plot shows group-mean pathway scores for the three groups of diseases. In general, there is pathway up-regulation in SLC group, even higher than that in SS, while down-regulation in CA group.
Network analysis Genome-level biological significance of the selected pathways was revealed by network analysis. Here, the network consisted of all KEGG pathways as nodes and substantial pairwise gene-overlap among pathways as edges. The centrality of the selected pathways was further quantified in terms of degree and betweenness centrality. Degree captures short-range connectivity of a node (i.e., how many nodes are connected to this node?), while betweenness centrality captures long-range centrality (i.e., how often this node falls on the shortest path between any two other nodes?) Degree captures the number of immediate neighbours of a node, while betweenness captures the essentiality of a node to the structure of the network. The degree and betweenness values for the selected 66 pathways were recorded (Additional File 5: Table S2). The degree distribution of the network showed scale-free property of a biological network, i.e., many nodes with few edges and a few nodes with large number of edges (Additional File 3: Figure S3 - panel A). Visual exploration revealed the selected pathways at the core of the network (Fig. 3), and this was confirmed by comparing the degree of these 66 pathways with other pathways in the human genome. As shown in Additional File 3: Figure S3 (panel B), selected pathways had higher degree than the other pathways.
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Fig. 3: KEGG overlap network is constructed with each KEGG pathway as a node and overlapping gene membership between two pathways as an edge. The selected 66 pathways are shown in red, while the other pathways are shown in grey. Red nodes (selected pathways) have more connecting edges than the grey nodes, thus representing hub-like nature of selected pathways. This suggests that key biological processes are perturbed in both SS and SLC.
Machine learning-based prediction of cancer group (SLC/CA) from 66 pathway scores In order to assess the clinical relevance of the selected pathways, we asked if it is possible to predict (by a machine learning algorithm) the cancer group based on the selected pathway scores of an individual patient of cancer. For each patient, 66 pathway scores were input for the classifier, with the expected output being SLC or CA. Five-fold cross-validation was employed with balanced partitioning in each fold. Both algorithms - Support Vector Machine (SVM) and Neural Net (NN) – performed with high accuracy in assigning the samples to their respective cancer groups. SVM correctly assigned 537 (99.08%) out of 542 patients , while NN correctly assigned 536 (98.89%) out of 542 patients, with a misclassification rate of 0.9% and 1.1% respectively (Table 2). This independent validation showed the clinical relevance of the selected 66 pathways for prediction of cancer group from individual patient-level data.
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Table 2: Two machine learning algorithms - Support Vector Machine (SVM) and Neural Network (NN) - were implemented through the function call MLearn (of R package MLInterfaces). SVM was applied with default parameters. Neural Network applied with three nodes in the hidden layer, with weight decay set to 0.01. Five-fold cross-validation was performed by generating a partition function (for cross-validation, where the partitions are approximately balanced with respect to the distribution of cancer tissue types (SLC or CA) in training and test sets in each fold. Confusion matrix from the classifier output was collected for calculation of misclassification rates. Predicted Support Vector Machine CA SLC
CA 349 1 Given SLC 4 188
Misclassification rate 0.9
Predicted Neural Network CA SLC
CA 347 3
Given SLC 3 189
Misclassification rate 1.1
Survival analysis Another measure of clinical relevance of pathway signature was provided by its association with survival. For a given pathway, the patients were divided into two groups of subjects (high-scoring and low-scoring) based on the level of pathway score. Survival probability for these two groups was assessed both graphically and statistically. For many of the pathways, there was a higher pathway score in survivors compared to non-survivors in SLC. This directionality was also maintained in SS, i.e., higher pathway score in survivors compared to non-survivors (Additional File 6: Table S3). The number of pathways associated (p < 0.1) with survival varied: 9 (14%) in HNSC, 28 (42%) in LIHC and 34 (52%) in KIRC (Fig. 4A). Representative plots were drawn to show survival difference between high-score and low-score patients for the pathway “Fc gamma R-mediated phagocytosis” (Fig. 4B-D).
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Fig. 4: (A) Three SLC studies were selected for survival analysis. For each cancer, association with survival was accepted at threshold of p < 0.1. For each cancer type, proportion of pathways associated with survival was calculated and converted to a percentage. The percentage values are presented in this bar plot. As shown, up to 50% of the pathways are associated with survival in the SLC group. (B-D) Kaplan-Meier plot showing significant association between pathway score and survival from the three SLC cancer types: HNSC (B), KIRC (C) and LIHC (D).
Functional classification of the pathways The selected 66 pathways were divided into categories based on their functional relevance. The categories included: immune system, infection, cancer, catabolism, signal transduction, ribosome biogenesis and carbohydrate metabolism (Additional File 8: Text S1).
Viral integration in TCGA samples Out of the 687 cancer samples from TCGA analysed by us, there was overlap of 425 (61.9%) samples with the samples analysed for viral integration by Tang et al. [25]; of the 425 samples, 120 belonged to SLC group, and 305 belonged to CA group. Viral integration was observed in 9 (7.5%) SLC samples and 2 (0.66%) CA samples, showing significantly (p = 0.0003) higher viral integration in SLC. In another study by Cao et al. [26], there was an overlap of 533 (77.6%) of 687 samples analysed by us. Of the 533, 200 (37.5%) were SLC while 333 (62.5%) were CA cancers. There was significantly (p = 0.001) higher viral integration in SLC (30%) compared to CA (17.4%). The report by Kazemian et al. [27] was not associated with supplementary sample-level data. However, re-analysis of summary data provided (Additional File 8: Table S5) led to the finding of significantly (p = 4.10E-13) higher viral integration in SLC (18.7%) compared to CA (5.6%). Over all, the findings were consistent with SLC cancers to have greater likelihood of prediction of viral integration.
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Discussion Comprehensive system-level analysis reveals shared transcriptomic response between septic shock (SS) and a subset of cancers (SLC). The SLC group predominantly consists of cancer of the upper GI tract, including head and neck, oesophagus, stomach, liver and biliary tract. The striking segregation of the SLC group with SS suggests shared elements of pathophysiology operational in these disorders. Sixty-six pathways differentially expressed in both SS and SLC represent critical biological processes, such as metabolism, immune response and protection against infection. Network analysis reveals the selected pathways as a core functional module (Figure 3) of the genome-scale network dysregulated in both SS and SLC. Many of these processes, such as metabolism and inflammatory response are known to contribute to the pathogenesis of both sepsis and cancer [9]. The segregation of cancer into two groups (SLC and CA) prompted us to investigate the prospect of the selected pathways as a classifier. Machine learning-based validation of an independent data set proved that the pathways indeed consist of a robust sample-level signature of the cancer groups. It is thus possible to predict, with high accuracy, whether a patient belongs to a particular cancer group (SLC or not). With plummeting costs and increasing acceptability of clinical transcriptomics, this signature may be useful in future for patient stratification. Similarity in the direction of change in pathway activity immediately evokes an explanation in terms of shared immunological response in either case. SLC are often associated with infection (i.e., human papilloma virus in “head and neck”, H. pylori in stomach, hepatitis viruses in liver). In fact, TCGA data analysed for the presence of viral sequence reads in RNA-seq datasets of several cancers have revealed infection status of the samples. Interestingly, the majority of the infected samples belong to the GI associated cancers including head and neck (HNSC), oesophagus (ESCA), stomach (STAD) and liver (LIHC) [25–29]. Cao et al. (2016) [26] estimated high percentage of infected samples in TCGA datasets for liver (21.2%), head and neck (16.6%), stomach (14.8%) and oesophagus (12%). It is known that sepsis starts out as an infection, but it is the uncontrolled host response that drives the phase of shock. Similarly, in cancers with an infectious origin, host response (e.g., inflammation) plays a role in malignant transformation [9]. Pathways related to immune response are consistently differentially expressed in both SS and SLC. Although the time scale of pathogenesis is much shorter in SS compared to cancer, our finding calls for greater attention into the shared cellular processes underlying these two distinct clinical phenotypes. The finding of pathway up-regulation associated with survival brings new insight into the relationship between the shared transcriptomic patterns and disease outcome. Sepsis is a highly lethal dysregulated host response to infection, and SLC, by extension, appears to share a part of that response. Since the pathways are selected on the basis of up-regulation in both SLC and SS (compared to control), plausible explanation is that the pathway up-regulation is protective rather than detrimental to the human host. It is worth mentioning that viral integration or bacterial infection in a setting of cancer has been reported to favour survival in SLC cancers of oropharyngeal [30], liver [31] and kidney [32]. Alteration of intestinal permeability is known in both sepsis and cancer [33]. It may be speculated that anatomical proximity increases the likelihood of the liver and upper gastrointestinal tissue to be exposed to the translocated microbial products through a permeable gut, eliciting a host response in both SS and SLC. Significant association between survival and up-regulation of phagocytosis-associated pathway (i.e., Fc gamma R-mediated phagocytosis) lends support to this view. In general, sepsis is less lethal in patients with cancer of the digestive system than cancer of other organs [8]. The role of gut in survival from sepsis and cancer is an active area of research with translational potential.
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Conclusions Firstly, transcriptome-based systems biology approach segregates cancer into two groups (SLC and CA) based on similarity with SS. Secondly, the similarity is based on a set of pathways associated with pathogenesis of sepsis and cancer. These pathways form a robust signature of a novel cancer grouping. Lastly, up-regulation of the pathways is protective rather than detrimental to the patient. A mechanism of the shared protective host response is hypothesized in terms of immunocompetence induced by microbial products from the permeable gut. This work is the first step towards a systems biology-based patient stratification. It is hoped that future work in this direction shall generate actionable knowledge for clinical management of both cancer and septic shock.
List of abbreviations: BLCA: Bladder Urothelial Carcinoma BRCA: Breast invasive carcinoma CA: Cancer Alone CHOL: Cholangiocarcinoma COAD: Colon adenocarcinoma ESCA: Esophageal carcinoma FPKM: Fragments Per Kilobase of transcript per Million mapped reads GEO: Gene Expression Omnibus HNSC: Head and Neck squamous cell carcinoma ICU: Intensive Care Unit KEGG: Kyoto Encyclopaedia of Genes and Genomes KICH: Kidney Chromophobe KIRC: Kidney renal clear cell carcinoma KIRP: Kidney renal papillary cell carcinoma LFC: log2(fold change) LIHC: Liver hepatocellular carcinoma LUAD: Lung adenocarcinoma LUSC: Lung squamous cell carcinoma NCBI: National Center for Biotechnology Information NN: Neural Net PRAD: Prostate adenocarcinoma READ: Rectum adenocarcinoma SLC: Sepsis-Like Cancers SS: Septic shock STAD: Stomach adenocarcinoma SVM: Support Vector Machine TCGA: The Cancer Genome Atlas THCA: Thyroid carcinoma UCEC: Uterine Corpus Endometrial Carcinoma Declarations − Ethics approval and consent to participate In this study, patient data from public databases (GEO and TCGA) have been analysed. We have not used any patient data that are not already available in the public domain.
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− Consent to publish Not applicable. − Availability of data and materials All programming was done in the R programming language [20]. Data and R code are available at the following link: https://figshare.com/ (https://doi.org/10.6084/m9.figshare.8118413.v3, https://doi.org/10.6084/m9.figshare.8118647.v5). The whole data can be downloaded as a single zip file (tcnibmgV3doc.zip). Upon uncompressing the zip, instructions for running the code and generating the figures of this manuscript are available in the file howto.pdf. − Competing interests The authors declare that they have no competing interests. − Funding This work was supported by an extramural grant (No. BT/PR16536/BID/7/652/2016, duration of 3 years, sanctioned on 30-03-2017) from the Department of Biotechnology, Government of India. − Authors' contributions SKM conceptualized the study and contributed to Funding Acquisition, Project Administration, Resources, Supervision. HT contributed to Data Curation. SM contributed to Data Curation, Software, Validation, Visualization. All authors contributed to Formal Analysis, Investigation, Methodology, Manuscript writing and approved of the final manuscript. − Acknowledgements We thank the National Cancer Institute for making TCGA data available in the public domain. We thank the National Center for Biotechnology Information for making GEO data available in the public domain. This study would not have been possible without data from these two resources. We thank the Director of National Institute of Biomedical Genomics for making the computational resources accessible to us. HT and SKM thank the Department of Biotechnology, Government of India for financial support to carry out the analysis.
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Supplementary Information
Supplementary Figure S1. For the 90 pathways significantly associated with SS, pathway scores were computed for the cancer studies. Scores for SS (6 studies) and cancer (17 studies) were subjected to hierarchical clustering (details in main text). As shown in this dendrogram, there is clear segregation of the cancer studies into two groups: sepsis−like (SLC) and other cancer (CA).
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Supplementary Figure S2. Gene level heat map of each of the selected 66 pathways. LFC for each gene was calculated from disease and normal samples (disease-normal) for all studies. For each disease type (CA, SLC or SS), median LFC was calculated across the studies in that disease type. Combined heat map was generated based on the pathway genes and the three disease groups. We considered only those genes which have similar LFC directionality in SLC and SS. Red colour represents up-regulation in disease compared to control, while green colour represents down- regulation. Pathway names with KEGG identifiers are shown on the top, gene symbol and names are row-labels of heat map. The major class (to which the pathway belongs) is shown at the bottom. (Go to the last part of the document after page 30)
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Supplementary Figure S3. (A) This is the degree distribution of the network generated by overlapping KEGG pathways. This shows that there are many nodes with very low connectivity but a few nodes with very high connectivity. This is consistent with the scale-free property of biological networks. (B) Box plot showing comparison of degree between two groups of nodes in this network - selected 66 and others. The higher value of the selected 66 nodes suggests that these are highly overlapping pathways forming a functional core of the human genome.
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Supplementary Table S1 . Selected 66 pathways with their significance and direction of regulation in all the studies. Coloured cells are a representation of pathway scores. Red indicates significant up-regulation, green indicates significant down-regulation and grey indicates non-significant change in pathway. Number of up- and down-regulated pathways in each study is shown at the top. Group membership (to CA, SLC or SS) is shown as a label on top of the code of the data set. First three columns of the sheet are pathway name, annotation (functional class) and KEGG ID respectively. Average number of up-regulated pathways 11 58 63 # Up-regulated30 10 5 1 13 19 19 3 4 9 13 63 63 57 42 62 60 63 63 63 63 63
# Down-regulated 0 393465201432 9 6 1232 1 1 0 8 1 0 3 3 3 3 3 CA SLC SS
Pathway name Annotation Pathway_id BLCA BRCA COAD KICH KIRP LUAD LUSC PRAD READ THCA UCEC LIHC CHOL HNSC KIRC ESCA STAD GSE13904 GSE26378 GSE26440 GSE4607 GSE8121 Pathways in cancer Cancer hsa05200 0 -1 -1 -1 0 0 0 0 0 0 -1 11111111111 Transcriptional misregulation in cancer Cancer hsa05202 0 -1 0 -1 0 0 0 0 0 0 -1 11111111111 Proteoglycans in cancer Cancer hsa05205 0 -1 -1 -1 0 0 -1 -1 0 0 -1 1 1 1 0 1 1 1 1 1 1 1 Renal cell carcinoma Cancer hsa05211 1 0 -1 -1 0 0 1 0 0 0 0 11111111111 Pancreatic cancer Cancer hsa05212 1 0 0 -1 0 1 1 0 0 0 0 11111111111 Glioma Cancer hsa05214 1 -1 -1 -1 0 1 1 0 0 1 0 11111111111 Prostate cancer Cancer hsa05215 1 0 0 -1 0 1 1 0 0 0 0 11111111111 Melanoma Cancer hsa05218 0 -1 0 -1 0 1 0 0 0 0 0 11111111111 Bladder cancer Cancer hsa05219 1 1 1 -1 0 1 1 0 11111111111111 Acute myeloid leukemia Cancer hsa05221 0 -1 -1 -1 0 0 0 0 0 0 -1 11111111111 Non-small cell lung cancer Cancer hsa05223 1 0 -1 -1 0 0 1 0 0 0 0 11111111111 Central carbon metabolism in cancer Cancer hsa05230 1 0 0 -1 0 1 1 0 0 0 111111111111 Choline metabolism in cancer Cancer hsa05231 0 -1 -1 -1 -1 0 0 0 0 -1 -1 1 1 1 0 1 1 1 1 1 1 1 Chemical carcinogenesis Cancer hsa05204 0 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 0 -1 -1 0 1 1 1 1 1 Galactose metabolism - Homo sapiens (human) Carbohydrate metabolism hsa00052 1 0 -1 -1 1 1 1 -1 -1 0 1 1 1 1 1 1 0 1 1 1 1 1 Glycolysis / Gluconeogenesis Carbohydrate metabolism hsa00010 1 -1 -1 -1 -1 1 1 -1 0 -1 1 1 0 0 -1 0 0 1 1 1 1 1 Pentose phosphate pathway Carbohydrate metabolism hsa00030 1 -1 1 -1 0 1 1 0 1 -1 1 1 1 0 0 1 1 1 1 1 1 1 Insulin signaling pathway Endocrine system hsa04910 1 -1 -1 -1 0 0 0 0 0 -1 0 1 1 1 0 1 1 1 1 1 1 1 GnRH signaling pathway Endocrine system hsa04912 0 -1 -1 -1 -1 -1 -1 0 0 0 -1 1 1 1 0 1 1 1 1 1 1 1 Progesterone-mediated oocyte maturation Endocrine system hsa04914 1 1 1 -1 0 1 1 0 0 0 1 1 1 1 0 1 1 1 1 1 1 1 Prolactin signaling pathway Endocrine system hsa04917 0 -1 0 -1 -1 0 -1 0 0 0 -1 1 1 1 0 1 1 1 1 1 1 1 Ovarian steroidogenesis Endocrine system hsa04913 0 -1 -1 -1 -1 -1 -1 0 -1 -1 -1 1 1 0 -1 0 0 1 1 1 1 1 Platelet activation Immune system hsa04611 0 -1 -1 -1 -1 -1 -1 0 0 0 -1 11111111111 Antigen processing and presentation Immune system hsa04612 0 1 0 -1 1 0 -1 0 0 0 0 1 1 1 1 1 1 -1 -1 -1 -1 -1 Toll-like receptor signaling pathway Immune system hsa04620 0 0 0 -1 1 0 -1 0 0 0 -1 11111111111 RIG-I-like receptor signaling pathway Immune system hsa04622 1 0 0 -1 0 1 0 0 0 0 0 11111111111 Fc epsilon RI signaling pathway Immune system hsa04664 0 -1 -1 -1 0 0 -1 0 0 0 -1 11111111111 Fc gamma R-mediated phagocytosis Immune system hsa04666 1 0 -1 -1 0 0 -1 0 0 0 0 11111111111 Leukocyte transendothelial migration Immune system hsa04670 0 -1 -1 -1 -1 -1 -1 -1 0 1 -1 11111111111 Bacterial invasion of epithelial cells Infectious disease hsa05100 1 0 -1 -1 1 0 0 0 0 1 -1 11111111111 Vibrio cholerae infection Infectious disease hsa05110 1 1 0 1 -1 1 0 0 0 0 1 1 1 1 -1 1 1 1 1 1 1 1 Epithelial cell signaling in Helicobacter pylori inf Infectious disease hsa05120 1 0 0 -1 -1 0 -1 0 0 1 0 1 1 1 -1 1 1 1 1 1 1 1 Salmonella infection Infectious disease hsa05132 0 -1 0 -1 1 -1 -1 0 0 1 -1 11111111111 Pertussis Infectious disease hsa05133 0 -1 0 -1 1 -1 -1 0 0 0 -1 11111111111 Legionellosis Infectious disease hsa05134 0 0 0 -1 0 0 -1 0 0 0 0 11111111111 Chagas disease (American trypanosomiasis) Infectious disease hsa05142 0 -1 -1 -1 0 0 -1 0 0 0 -1 11111111111 Amoebiasis Infectious disease hsa05146 0 -1 0 -1 0 0 -1 -1 0 0 -1 11111111111 Tuberculosis Infectious disease hsa05152 0 0 0 -1 0 0 -1 0 0 0 0 11111111111 Hepatitis C Infectious disease hsa05160 1 0 0 -1 0 1 0 0 0 0 0 1 1 1 0 1 1 1 1 1 1 1 Hepatitis B Infectious disease hsa05161 1 0 0 -1 1 1 1 0 0 0 0 11111111111 Glycerophospholipid metabolism Other hsa00564 1 -1 -1 -1 0 0 -1 0 0 0 0 1 1 1 0 1 1 1 1 1 1 1 Ribosome biogenesis in eukaryotes Other hsa03008 1 1 1 -1 1 1 1 1 1 -1 1 1 1 1 1 1 1 -1 -1 -1 -1 -1 p53 signaling pathway Other hsa04115 1 1 1 -1 1 1 1 0 11111111111111 Dorso-ventral axis formation Other hsa04320 0 -1 -1 -1 -1 0 -1 0 0 -1 -1 1 1 0 1 1 1 1 1 1 1 1 Osteoclast differentiation Other hsa04380 0 -1 -1 -1 1 -1 -1 0 0 0 -1 0 1 1 1 1 1 1 1 1 1 1 Focal adhesion Other hsa04510 0 -1 -1 -1 -1 0 -1 -1 0 0 -1 11111111111 Adherens junction Other hsa04520 1 -1 0 -1 0 0 0 0 0 0 -1 1 1 1 0 1 1 1 1 1 1 1 Synaptic vesicle cycle Other hsa04721 1 1 -1 -1 -1 0 0 0 -1 0 1 1 1 0 -1 1 1 1 1 1 1 1 Regulation of actin cytoskeleton Other hsa04810 0 -1 -1 -1 0 0 -1 -1 -1 0 -1 1 1 1 0 1 1 1 1 1 1 1 Amyotrophic lateral sclerosis (ALS) Other hsa05014 0 -1 -1 -1 1 1 1 0 0 1 0 11111111111 Alcoholism Other hsa05034 1 1 0 -1 0 1 1 1 0 0 111111111111 Primary immunodeficiency Other hsa05340 0 0 -1 -1 1 0 -1 0 0 0 0 1 1 1 1 1 1 -1 -1 -1 -1 -1 Vitamin digestion and absorption Other hsa04977 1 -1 0 -1 -1 -1 -1 1 0 -1 1 0 0 0 -1 0 0 1 1 1 1 1 Morphine addiction Other hsa05032 0 -1 -1 -1 -1 -1 -1 -1 -1 0 -1 1 1 0 0 1 0 1 1 1 1 1 MAPK signaling pathway Signal transduction hsa04010 0 -1 -1 -1 -1 -1 -1 0 0 -1 -1 1 1 1 0 1 1 1 1 1 1 1 ErbB signaling pathway Signal transduction hsa04012 200 -1 -1 -1 0 0 1 0 0 0 -1 1 1 1 0 1 1 1 1 1 1 1 bioRxiv preprint doi: https://doi.org/10.1101/635243; this version posted February 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.
Supplementary Table S2: This table contains the property of each node of the network. Degree of a node is the number of edges connected to a node. Betweenness centrality is a measure of how much information flows through a specific node, i.e., average number of shortest paths passing through the node. Degree refers to the number of neighbours of a node while betweenness centrality refers to how important the node is for maintaining the overall structure of that network. The two nodes with highest betweenness centrality (Glycolysis/Gluconeogenesis, Lysosome) in the network are highlighted.
Betweenness KEGG Pathway Names KEGG ID Degree Centrality
Vitamin digestion and absorption hsa04977 NA NA
Ribosome biogenesis in eukaryotes hsa03008 NA NA
Glycolysis / Gluconeogenesis hsa00010 26 1599.07
Lysosome hsa04142 7 680.2
Insulin signaling pathway hsa04910 89 560.44
Epithelial cell signaling in Helicobacter pylori infection hsa05120 49 520.57
AMPK signaling pathway hsa04152 62 520.28
Vibrio cholerae infection hsa05110 37 439.59
Choline metabolism in cancer hsa05231 90 433.04
Tuberculosis hsa05152 87 410.94
Central carbon metabolism in cancer hsa05230 81 403.15
Ovarian steroidogenesis hsa04913 48 387.79
GnRH signaling pathway hsa04912 107 383.52
Hepatitis B hsa05161 106 347.57
Chagas disease (American trypanosomiasis) hsa05142 104 328.8
HIF-1 signaling pathway hsa04066 80 323.29
Fc epsilon RI signaling pathway hsa04664 102 317.94
Pertussis hsa05133 67 295.91
Progesterone-mediated oocyte maturation hsa04914 103 287.93
Pathways in cancer hsa05200 98 286.47
VEGF signaling pathway hsa04370 103 265.42
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Amoebiasis hsa05146 99 248.79
Proteoglycans in cancer hsa05205 100 230.53
FoxO signaling pathway hsa04068 90 206.86
Phagosome hsa04145 31 195.33
PI3K-Akt signaling pathway hsa04151 80 176.5
Fc gamma R-mediated phagocytosis hsa04666 83 170.39
MAPK signaling pathway hsa04010 90 167.12
Platelet activation hsa04611 100 166.21
Toll-like receptor signaling pathway hsa04620 91 156.38
Rap1 signaling pathway hsa04015 96 153.11
Morphine addiction hsa05032 46 152.64
Prostate cancer hsa05215 95 150.98
Glioma hsa05214 97 145.97
TNF signaling pathway hsa04668 91 136.56
Hepatitis C hsa05160 91 131.46
Antigen processing and presentation hsa04612 26 123.22
Bacterial invasion of epithelial cells hsa05100 56 116.33
Pancreatic cancer hsa05212 91 101.47
Osteoclast differentiation hsa04380 87 97.12
Focal adhesion hsa04510 80 90.01
Acute myeloid leukemia hsa05221 84 78.81
Chemical carcinogenesis hsa05204 14 75.3
Leukocyte transendothelial migration hsa04670 66 72.24
Non-small cell lung cancer hsa05223 86 64.38
Salmonella infection hsa05132 48 61.81
Alcoholism hsa05034 46 60.62
Regulation of actin cytoskeleton hsa04810 62 60.6
Jak-STAT signaling pathway hsa04630 61 58.74
Prolactin signaling pathway hsa04917 91 57.33
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Renal cell carcinoma hsa05211 84 56.81
ErbB signaling pathway hsa04012 91 56.53
Melanoma hsa05218 81 45.43
Synaptic vesicle cycle hsa04721 10 42.04
Galactose metabolism hsa00052 8 41.96
Amyotrophic lateral sclerosis (ALS) hsa05014 30 39.8
Glycerophospholipid metabolism hsa00564 14 26.42
Bladder cancer hsa05219 53 18.91
Adherens junction hsa04520 27 17.54
RIG-I-like receptor signaling pathway hsa04622 39 17.21
Legionellosis hsa05134 27 9.08
Dorso-ventral axis formation hsa04320 26 2
p53 signaling pathway hsa04115 14 1.21
Transcriptional misregulation in cancer hsa05202 6 0.78
Primary immunodeficiency hsa05340 5 0.29
Pentose phosphate pathway hsa00030 3 0
23 bioRxiv preprint doi: https://doi.org/10.1101/635243; this version posted February 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.
Supplementary Table S3: Three SLC cancers were selected for survival analysis. The value in each cell corresponds to the p-value for association of the pathway with the cancer type. At a threshold of p < 0.1, the cell has been high-lighted, noting significant association of the pathway with survival from cancer. Direction of pathway expression score was estimated from visual inspection of survival plot in the SLC cancers. For each cancer, proportion of pathways associated with survival was calculated and converted to percentage (bottom row of the table). For septic shock, pathway score was calculated in the survivor group compared to the non- survivor group, as described in the Methods. A direction of “High” was assigned, if the pathway was observed to be higher in the survivor group for four or more of the eight septic shock data sets tested. Otherwise, the direction of “Low” was assigned.
P-value Direction in Survivors
SLC group SLC group Septic Association with survival Shock HNSC KIRC LIHC HNSC KIRC LIHC
Glycolysis / Gluconeogenesis | hsa00010 0.07 0.84 0.24 Low - Low High
Pentose phosphate pathway | hsa00030 0.81 0.74 0.26 - - Low High
Galactose metabolism | hsa00052 0.99 0.61 0.99 - High - High
Glycerophospholipid metabolism | hsa00564 0.63 0.65 0.88 - - - High
Ribosome biogenesis in eukaryotes | hsa03008 0.26 0.40 0.62 High - - High
MAPK signaling pathway | hsa04010 0.53 0.12 0.04 - High High High
ErbB signaling pathway | hsa04012 0.08 0.08 0.22 High High - High
Rap1 signaling pathway | hsa04015 0.51 0.03 0.01 - High High High
HIF-1 signaling pathway | hsa04066 0.22 0.04 0.16 Low High - High
FoxO signaling pathway | hsa04068 0.27 0.00 0.74 Low High - High
p53 signaling pathway | hsa04115 0.50 0.24 0.44 - High - Low
Lysosome | hsa04142 0.55 0.31 0.13 - High High High
Phagosome | hsa04145 0.98 0.92 0.15 - - High High
PI3K-Akt signaling pathway | hsa04151 0.88 0.15 0.00 - High High High
AMPK signaling pathway | hsa04152 0.81 0.00 0.95 - High - High
24 bioRxiv preprint doi: https://doi.org/10.1101/635243; this version posted February 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.
Dorso-ventral axis formation | hsa04320 0.01 0.01 0.04 High High High High
VEGF signaling pathway | hsa04370 0.27 0.04 0.02 - High High High
Osteoclast differentiation | hsa04380 0.88 0.21 0.08 - High High High
Focal adhesion | hsa04510 0.77 0.12 0.00 - High High High
Adherens junction | hsa04520 0.20 0.01 0.01 High High High High
Platelet activation | hsa04611 0.96 0.10 0.00 - High High High
Antigen processing and presentation | hsa04612 0.74 0.14 0.02 - High High High
Toll-like receptor signaling pathway | hsa04620 0.85 0.17 0.55 - High High High
RIG-I-like receptor signaling pathway | hsa04622 0.92 0.11 0.44 - High - High
Jak-STAT signaling pathway | hsa04630 0.96 0.08 0.62 - High - High
Fc epsilon RI signaling pathway | hsa04664 0.06 0.04 0.06 High High High High
Fc gamma R-mediated phagocytosis | hsa04666 0.10 0.01 0.01 High High High High
TNF signaling pathway | hsa04668 0.50 0.06 0.48 High High High High
Leukocyte transendothelial migration | hsa04670 0.43 0.00 0.05 - High High High
Synaptic vesicle cycle | hsa04721 0.78 0.97 0.11 - - High High
Regulation of actin cytoskeleton | hsa04810 0.76 0.01 0.01 - High High High
Insulin signaling pathway | hsa04910 0.72 0.01 0.47 - High High High
GnRH signaling pathway | hsa04912 0.08 0.21 0.15 High High High High
Ovarian steroidogenesis | hsa04913 0.99 0.02 0.80 - High - High
Progesterone-mediated oocyte maturation | hsa04914 0.80 0.03 0.18 - High - High
Prolactin signaling pathway | hsa04917 0.12 0.02 0.53 High High - High
Vitamin digestion and absorption | hsa04977 0.84 0.35 0.97 - Low - High
Amyotrophic lateral sclerosis (ALS) | hsa05014 0.14 0.11 0.26 - High High High
Morphine addiction | hsa05032 0.20 0.28 0.02 - High High High
Alcoholism | hsa05034 0.28 0.03 0.11 High High High High
Bacterial invasion of epithelial cells | hsa05100 0.49 0.10 0.04 - High High High
Vibrio cholerae infection | hsa05110 0.21 0.67 0.24 High - High High
25 bioRxiv preprint doi: https://doi.org/10.1101/635243; this version posted February 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.
Epithelial cell signaling in Helicobacter pylori infection | hsa05120 0.12 0.21 0.57 High High High High
Salmonella infection | hsa05132 0.07 0.55 0.38 High - High High
Pertussis | hsa05133 0.98 0.50 0.39 - - High High
Legionellosis | hsa05134 0.31 0.98 0.63 High - High High
Chagas disease (American trypanosomiasis) | hsa05142 0.71 0.10 0.12 - High High High
Amoebiasis | hsa05146 0.67 0.92 0.03 - - High High
Tuberculosis | hsa05152 0.99 0.96 0.01 - - High High
Hepatitis C | hsa05160 0.32 0.03 0.32 High High High High
Hepatitis B | hsa05161 0.19 0.05 0.14 High High High High
Pathways in cancer | hsa05200 0.67 0.01 0.01 - High High High
Transcriptional misregulation in cancer | hsa05202 0.80 0.44 0.06 - - High High
Chemical carcinogenesis | hsa05204 0.80 0.05 0.02 - Low Low High
Proteoglycans in cancer | hsa05205 0.84 0.06 0.04 - High High High
Renal cell carcinoma | hsa05211 0.60 0.04 0.08 - High High High
Pancreatic cancer | hsa05212 0.45 0.01 0.28 High High High High
Glioma | hsa05214 0.61 0.16 0.07 - High High High
Prostate cancer | hsa05215 0.39 0.01 0.02 - High High High
Melanoma | hsa05218 0.59 0.10 0.01 - High High High
Bladder cancer | hsa05219 0.00 0.00 0.03 High High High High
Acute myeloid leukemia | hsa05221 0.47 0.00 0.76 - High - High
Non-small cell lung cancer | hsa05223 0.57 0.02 0.57 High High - High
Central carbon metabolism in cancer | hsa05230 0.69 0.02 0.10 - High High High
Choline metabolism in cancer | hsa05231 0.04 0.01 0.03 High High High High
Primary immunodeficiency | hsa05340 0.77 0.22 0.31 - High High High
Fraction of pathways associated with survival 0.14 0.52 0.42
26 bioRxiv preprint doi: https://doi.org/10.1101/635243; this version posted February 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.
Supplementary Table S4: List of additional cancer data sets for machine learning-based prediction of cancer samples.
Number Number of of Number Type of tumour control GEO_ID Cancer of Platform Normalization tumour samples samples samples used in used in analysis analysis
Breast, Colorectal, GPL13158[HT_HG- Prostate, And Non- Solid U133_Plus_PM] GSE103512 280 242 38 Quantile Small Cell Lung Tumor Affymetrix HT HG- Cancer U133+ PM Array Plate
GPL570 [HG- U133_Plus_2] Hepatocellular Solid GSE112790 198 183 15 Affymetrix Human Quantile Carcinoma Tumor Genome U133 Plus 2.0 Array
GPL6102Illumina Lung Solid GSE32665 170 85 85 human-6 v2.0 expression Quantile adenocarcinoma Tumor beadchip
GPL6480 Agilent- 014850 Whole Human Lung squamous Solid Natural log of GSE33479 122 14 27 Genome Microarray carcinogenesis Tumor (Cy5/Cy3) 4x44K G4112F (Probe Name version)
GPL17586 [HTA-2_0] Affymetrix Human Solid GSE84984 Colorectal Cancer 15 9 6 Transcriptome Array 2.0 RMA Tumor [transcript (gene) version]
GPL4133Agilent- 014850 Whole Human Solid GSE103236 Gastric Cancer 19 9 9 Genome Microarray Lowess Tumor 4x44K G4112F (Feature Number version)
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Supplemental Table S5: Viral integration in TCGA samples. Results are derived from published data.
Tang2013 [a] Cao2016 [b] Kazemina2015 [c] **
N (%) P-value N (%) P-value N (%) P-value
Samples analysed in current 687 687 N.A. manuscript
Overlap with published study 425 533 N.A. (61.9%) (77.6%)
SLC samples 120 200 305 (28.2%) (37.5%)
CA samples 305 3.00E-04 333 1.00E-03 1175 4.10E-13 (71.8%) (62.5%)
Viral integration in SLC 9 (7.5%) 60 (30%) 57 (18.7%)
Viral integration in CA 2 (0.66 %) 58 (17.4 66 (5.6%) %)
** Sample-level data are not available. Number and proportion of viral integration in SLC and CA samples are calculated from summary data provided in the publication (Table 1 of [c]).
[a] Tang KW, Alaei-Mahabadi B, Samuelsson T, Lindh M, Larsson E. The landscape of viral expression and host gene fusion and adaptation in human cancer. Nature Communications. 2013;4:1–9.
[b] Cao S, Wendl MC, Wyczalkowski MA, Wylie K, Ye K, Jayasinghe R, et al. Divergent viral presentation among human tumors and adjacent normal tissues. Scientific Reports. 2016;6 June:1–12.
[c] Kazemian M, Ren M, Lin J-X, Liao W, Spolski R, Leonard WJ. Possible Human Papillomavirus 38 Contamination of Endometrial Cancer RNA Sequencing Samples in The Cancer Genome Atlas Database. Journal of Virology. 2015;89:8967–73.
28 bioRxiv preprint doi: https://doi.org/10.1101/635243; this version posted February 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.
Additional text : Functional classification of the pathways The selected 66 pathways are divided into categories based on their functional relevance. The categories include catabolism, immune system, infection, cancer, signal transduction, ribosome biogenesis and carbohydrate metabolism. Many of these pathways are related to immune response to infection, such as, clot formation, proinflammatory effects, antiviral effects, chemotactic effects and T cell stimulation, degranulation, cytokine gene transcription and generation of eicosanoids, phagocytosis, and migration of leukocytes to the site of injury, and are consistently up-regulated in both SS and SLC group. Catabolism Two catabolic pathways namely, Lysosome and Phagosome, are observed to be mostly up- regulated in SS and SLC (Fig. 2, Additional File 4: Table S1). Upon network analysis, it is revealed that lysosome pathway has a very high value for betweenness centrality (680.2) (Additional File 5: Table S2), thus being essential to the structure of the network. Likewise, Phagosome, another catabolic pathway linked to lysosome, is uniformly up regulated in SS and SLC groups (Additional File 2: Figure S2). Muscle wasting is one of the most common phenomena in both SS and cancer. Lysosome mediated protein degradation has been noted on a substantial scale in such cases. Further, transcriptome based meta-analysis conducted by Ma et al., reported up-regulation of lysosome pathway in sepsis while increased biogenesis of lysosomes has been observed in cancer cells. In this study, we observe consistent up-regulation of catabolic pathways associated with lysosome and phagosome in SS and SLC, suggesting high catabolic rate in both the groups. Besides, lysosome is now considered a hub of metabolic signalling given its key role in maintaining cellular homeostasis. It also appears as a central node in our network with high betweenness centrality. Immune system Both cancer and septic shock are associated with dysregulation in immune function. It is observed that immune system pathways associated with clot formation (Platelet activation), proinflammatory effects, antiviral effects, chemotactic effects and T cell stimulation (Toll-like receptor signalling pathway), degranulation, cytokine gene transcription and generation of eicosanoids (Fc epsilon RI signalling pathway), phagocytosis (Fc gamma R-mediated phagocytosis), and migration of leukocytes to the site of injury (Leukocyte transendothelial migration) are uniformly up regulated in both SS and SLC groups (Additional File 2: Figure S2). Infection Infection is a common theme in both septic shock (which originates as sepsis) and many cancers (known to be induced by microbial infection). Many infection-associated pathways, such as, Bacterial invasion of epithelial cells, Vibrio cholerae infection, Epithelial cell signalling in Helicobacter pylori infection, Salmonella infection, Pertussis, Legionellosis, Tuberculosis, Chagas disease (American trypanosomiasis), Amoebiasis, Hepatitis C and Hepatitis B are significantly up regulated in SS and SLC group (Additional File 2: Figure S2). Cancer pathways Many cancer-associated pathways, such as Transcriptional misregulation in cancer, Proteoglycans in cancer, Central carbon metabolism in cancer, Choline metabolism in cancer, Chemical carcinogenesis, Renal cell carcinoma, Pancreatic cancer, Glioma, Prostate cancer, Melanoma, Bladder cancer, Acute myeloid leukemia, Non-small cell lung cancer are up regulated in SS and SLC group (Additional File 2: Figure S2).
29 bioRxiv preprint doi: https://doi.org/10.1101/635243; this version posted February 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.
Signal transduction Signal transduction pathways involved in cell proliferation, differentiation, adhesion, migration, survival, cell cycle progression, anti-apoptosis (MAPK, ErbB, Rap1, VEGF, JAK-STAT and PI3k-Akt signalling pathways) and cell cycle regulation, apoptosis, autophagy, oxidative stress response, DNA repair, immune regulation, muscle atrophy, growth arrest, leukocyte recruitment and activation, synthesis of inflammatory mediators, remodelling of extracellular matrix (HIF1, AMPK, FoxO and TNF signalling pathways) are uniformly up-regulated in SS group, and in most of the SLC group (Additional File 2: Figure S2). Endocrine system Five pathways associated with endocrine system viz., Insulin signalling, GnRH signalling, Progesterone-mediated oocyte maturation, Prolactin signalling pathway and Ovarian steroidogenesis are up-regulated in all SS groups as well as in SLC group (Additional File 2: Figure S2). Carbohydrate metabolism Carbohydrate metabolism pathways including Galactose metabolism, Glycolysis/Gluconeogenesis, and Pentose phosphate pathway are up-regulated in SS group and most of the SLC group cancers. In our study, Galactose metabolism pathway is up-regulated in SLC and SS groups. Glycolysis/Gluconeogenesis (a source of energy and metabolite precursors of other pathways) plays a central role in cell as reflected by highest betweenness centrality parameter value i.e. 1599.06 (Additional File 5: Table S2). Pentose phosphate pathway, which generates precursors for synthesis of purine, pyrimidine and histidine, is up-regulated across the SS group along with the LIHC, CHOL, ESCA and STAD of SLC group.
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Gene−level heatmap for 66 pathways Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS Chemical carcinogenesis available undera SULT2A1 |sulfotransferase family 2Amember1 ALDH3B2 |aldehyde dehydrogenase 3family memberB2 CYP2E1 |cytochromeP450family 2subfamily Emember1 ADH1A |alcoholdehydrogenase 1A(classI),alphapolypeptide GSTA4 |glutathioneS−transferase alpha4 GSTA1 |glutathioneS−transferase alpha1 CYP1A2 |cytochromeP450family 1subfamily Amember2 UGT2B28 |UDPglucuronosyltransferase family 2memberB28 GSTM1 |glutathioneS−transferase mu 1 KYAT3 |kynurenine aminotransferase 3 GSTO2 |glutathioneS−transferase omega2 ALDH1A3 |aldehyde dehydrogenase 1family memberA3 UGT1A8 |UDPglucuronosyltransferase family 1memberA8 UGT2B17 |UDPglucuronosyltransferase family 2memberB17 GSTK1 |glutathioneS−transferase kappa1 GSTO1 |glutathioneS−transferase omega1 KYAT1 |kynurenine aminotransferase 1 hydrocarbonARNT |aryl receptornuclear translocator GSTM2 |glutathioneS−transferase mu 2 ADH5 |alcoholdehydrogenase 5(classIII),chipolypeptide MGST3 |microsomalglutathioneS−transferase 3 ALDH3B1 |aldehyde dehydrogenase 3family memberB1 ADH1B |alcoholdehydrogenase 1B(classI),betapolypeptide hsa05204 Cancer ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Bladder cancer MMP1 | matrix metallopeptidase 1 MMP1 |matrix BRAF |B−Rafproto−oncogene, kinase serine/threonine KRAS |proto−oncogene, GTPase ERBB2 |erb−b2receptortyrosinekinase2 proteinS6kinaseA5 RPS6KA5 |ribosomal growth factorEGF |epidermal MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 factorE2F3 |E2Ftranscription 3 factorE2F2 |E2Ftranscription 2 MDM2 |proto−oncogene DAPK2 |deathassociatedproteinkinase2 FGFR3 |fibroblast growth factor receptor3 MAPK1 |mitogen−activated proteinkinase1 factorE2F1 |E2Ftranscription 1 ARAF |A−Rafproto−oncogene, kinase serine/threonine growth factorEGFR |epidermal receptor THBS1 |thrombospondin1 CDKN2A |cyclindependentkinaseinhibitor2A NRAS |proto−oncogene, GTPase DAPK3 |deathassociatedproteinkinase3 VEGFA |vascular endothelialgrowth factor A corepressor 1 RB1 |RBtranscriptional MAPK3 |mitogen−activated proteinkinase3 metallopeptidase 2 MMP2 |matrix metallopeptidase 9 MMP9 |matrix TYMP |thymidine phosphorylase hsa05219 Cancer ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Pathways incancer MMP1 | matrix metallopeptidase1 MMP1 |matrix GNG4 |Gproteinsubunit gamma4 classreceptor3 FZD3 |frizzled RAC3 |Racfamily smallGTPase 3 classreceptor9 FZD9 |frizzled WNT16 |Wntfamily member 16 subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory WNT5A |Wntfamily member5A LAMA1 |lamininsubunit alpha1 SHH |sonichedgehog GNG13 |Gproteinsubunit gamma13 ELOB |elonginB GNB3 |Gproteinsubunit beta3 WNT8B |Wntfamily member8B BRCA2 |BRCA2,DNArepairassociated classreceptor10 FZD10 |frizzled ELOC |elonginC FGF5 |fibroblast growth factor 5 kinase BRAF |B−Rafproto−oncogene, serine/threonine FGF4 |fibroblast growth factor 4 PRKACG |proteinkinasecAMP−activated catalyticsubunit gamma LPAR3 |lysophosphatidic acidreceptor3 FGF6 |fibroblast growth factor 6 LPAR2 |lysophosphatidic acidreceptor2 FGF17 |fibroblast growth factor 17 FGF20 |fibroblast growth factor 20 FGF22 |fibroblast growth factor 22 NCOA4 |nuclear receptorcoactivator 4 FGF14 |fibroblast growth factor 14 LPAR4 |lysophosphatidic acidreceptor4 KRAS |proto−oncogene, GTPase WNT1 |Wntfamily member1 FGF19 |fibroblast growth factor 19 CCNE2 |cyclinE2 PRKCG |proteinkinaseCgamma WNT9B |Wntfamily member9B FGF11 |fibroblast growth factor 11 ERBB2 |erb−b2receptortyrosinekinase2 CCNA1 |cyclinA1 PLCB4 |phospholipaseCbeta4 BIRC7 |baculoviral IAPrepeatcontaining7 subunitITGA2 |integrin alpha2 MSH3 |mutS homolog3 ARHGEF11 |Rhoguaninenucleotide exchange factor 11 BDKRB1 |bradykinin receptorB1 BID |BH3interacting domaindeathagonist kinase36 STK36 |serine/threonine MAX |MYCassociatedfactor X bindingprotein2 CTBP2 |C−terminal PTCH2 |patched2 growth factorEGF |epidermal FGF12 |fibroblast growth factor 12 GNGT1 |Gproteinsubunit gammatransducin 1 VHL |von Hippel−Lindautumorsuppressor SUFU |negative regulatorofhedgehogsignaling MAP2K2 |mitogen−activated proteinkinase2 CSF3R |colony stimulating factor 3receptor MAP2K1 |mitogen−activated proteinkinase1 BCR |BCR,RhoGEFandGTPase activating protein FGF9 |fibroblast growth factor 9 factorE2F3 |E2Ftranscription 3 PRKACB |proteinkinasecAMP−activated catalyticsubunit beta FLT3 |fmsrelatedtyrosinekinase3 CREBBP |CREBbindingprotein GNG7 |Gproteinsubunit gamma7 APPL1 |adaptorprotein,phosphotyrosineinteracting withPHdomainandleucinezipper1 WNT4 |Wntfamily member4 GNAI3 |Gproteinsubunit alphai3 GSK3B |glycogensynthasekinase3beta factorE2F2 |E2Ftranscription 2 MDM2 |proto−oncogene DAPK2 |deathassociatedproteinkinase2 FGF1 |fibroblast growth factor 1 subunit 2 CKS2 |CDC28proteinkinaseregulatory CTNNA1 |cateninalpha1 SMAD4 |SMADfamily member4 GNAI1 |Gproteinsubunit alphai1 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha RASGRP4 |RASguanyl releasingprotein4 RBX1 |ring−box 1 CDK2 |cyclindependentkinase2 KIT |proto−oncogenereceptortyrosinekinase PTCH1 |patched1 CCNE1 |cyclinE1 ARHGEF12 |Rhoguaninenucleotide exchange factor 12 PLD1 |phospholipaseD1 GNB2 |Gproteinsubunit beta2 BAD |BCL2associatedagonistofcelldeath SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 RXRB |retinoidXreceptorbeta TFG |TRK−fusedgene EGLN1 |egl−9family hypoxia inducible factor 1 FGFR3 |fibroblast growth factor receptor3 GNG5 |Gproteinsubunit gamma5 GNG8 |Gproteinsubunit gamma8 STAT3TPR |translocated promoterregion,nuclear basket |signaltransducer and activator protein 3 oftranscription FADD |Fas associatedviadeathdomain MAPK1 |mitogen−activated proteinkinase1 CBL |Cbl proto−oncogene FOXO1 |forkhead box O1 IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma factorE2F1 |E2Ftranscription 1 PTEN |phosphataseandtensinhomolog PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma kinase ARAF |A−Rafproto−oncogene, serine/threonine BCL2L1 |BCL2like 1 hydrocarbon receptor nuclearARNT |aryl translocator growth factorEGFR |epidermal receptor DVL2 |dishevelled protein2 segmentpolarity RAC1 |Racfamily smallGTPase 1 APC |APC, WNTsignalingpathway regulator RXRG |retinoidXreceptorgamma RHOA |ras homologfamily memberA helix−loop−helixubiquitouskinase CHUK |conserved oxideNOS2 |nitric synthase2 EP300 |E1Abindingproteinp300 RELA |proto−oncogene, NF−kBsubunit WNT2 |Wntfamily member2 TGFBR1 |transforming growth factor betareceptor1 GNB1 |Gproteinsubunit beta1 GNAQ |Gproteinsubunit alphaq DVL3 |dishevelled protein3 segmentpolarity CASP8 |caspase8 RALBP1 |ralA bindingprotein1 ADCY6 |adenylate cyclase 6 CDC42 |celldivisioncycle42 PLCB2 |phospholipaseCbeta2 WNT10A |Wntfamily member10A XIAP |X−linked inhibitorofapoptosis GLI1 |GLIfamily zincfinger1 RASSF5 |Rasassociationdomainfamily member5 GLI3 |GLIfamily zincfinger3 EGLN3 |egl−9family hypoxia inducible factor 3 EGLN2 |egl−9family hypoxia inducible factor 2 PAX8 |pairedbox 8 MET |proto−oncogene, receptortyrosinekinase TGFB3 |transforming growth factor beta3 BIRC5 |baculoviral IAPrepeatcontaining5 CDKN2A |cyclindependentkinaseinhibitor2A CRK |proto−o hsa05200 Cancer ; this versionpostedFebruary19,2020. 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CA doi: https://doi.org/10.1101/635243 Transcriptional misregulationincancer SLC
SS available undera SIX4 |SIXhomeobox 4 SIX1 |SIXhomeobox 1 MYCN |proto−oncogene, factor bHLHtranscription PAX7 |pairedbox 7 peptidaseinhibitor,SPINT1 |serine Kunitz type1 HMGA2 |highmobilitygroupAT−hook 2 repeatcontaining,Y−linked tetratricopeptide UTY |ubiquitouslytranscribed WNT16 |Wntfamily member 16 TLX3 |T−cellleukemia homeobox 3 HIST1H3E |histonecluster1H3family membere HIST3H3 |histonecluster3H3 SSX1 |SSXfamily member 1 3 IL3 |interleukin CEBPE |CCAAT/enhancer binding proteinepsilon CCNA1 |cyclinA1 ETV4 |ETSvariant 4 BMP2K |BMP2inducible kinase MAX |MYCassociatedfactor X PLAU |plasminogenactivator, urokinase HIST1H3H |histonecluster1H3family memberh growthNGFR |nerve factor receptor LDB1 |LIMdomainbinding1 CCNT1 |cyclinT1 FLT3 |fmsrelatedtyrosinekinase3 H3F3A |H3histonefamily member3A PBX3 |PBXhomeobox 3 MDM2 |proto−oncogene REL |proto−oncogene, NF−kBsubunit ETV1 |ETSvariant 1 ZBTB17 |zincfingerandBTBdomaincontaining17 NCOR1 |nuclear receptorcorepressor1 renalcellcarcinoma(translocation−associated) PRCC |papillary DDIT3 |DNAdamageinducible 3 transcript 1receptortype2 IL1R2 |interleukin FCGR1A |Fcfragment ofIgGreceptorIa HOXA11 |homeobox A11 RXRB |retinoidXreceptorbeta likeKLF3 |Kruppel factor 3 BCL6 |B−cellCLL/lymphoma6 DUSP6 |dualspecificityphosphatase6 factorMAF |bZIPtranscription NUPR1 |nuclear regulator protein1,transcriptional SMAD1 |SMADfamily member 1 factorSP1 |Sp1transcription FOXO1 |forkhead box O1 NSD2 |nuclear receptorbindingSETdomainprotein2 TAF15 |TATA−boxMLLT1 bindingproteinassociatedfactor 15 |MLLT1, superelongationcomplex subunit KDM6A |lysinedemethylase 6A BCL2L1 |BCL2like 1 ETV6 |ETSvariant 6 JMJD1C |jumonjidomaincontaining1C EWSR1 |EWSRNAbindingprotein1 GOLPH3 |golgiphosphoprotein3 RXRG |retinoidXreceptorgamma ETV5 |ETSvariant 5 FUS |RNAbindingprotein RELA |proto−oncogene, NF−kBsubunit DOT1L |DOT1 like histonelysinemethyltransferase CDK9 |cyclindependentkinase9 metallopeptidase3 MMP3 |matrix ID2 |inhibitorofDNAbinding2 PAX8 |pairedbox 8 MET |proto−oncogene, receptortyrosinekinase CDK14 |cyclindependentkinase14 ETV7 |ETSvariant 7 hydrocarbon receptornuclearARNT2 |aryl translocator 2 NFKB1 |nuclear factor kappaBsubunit 1 CEBPA |CCAAT/enhancer bindingproteinalpha SPI1 |Spi−1proto−oncogene subunitITGAM |integrin alphaM CD14 |molecule PML |promyelocytic leukemia HOXA10 |homeobox A10 factorTFE3 |transcription bindingtoIGHMenhancer3 BCL2A1 |BCL2relatedproteinA1 PPARG |peroxisome proliferator activated receptorgamma FLI1 |Fli−1proto−oncogene, factor ETStranscription CEBPB |CCAAT/enhancer bindingproteinbeta LMO2 |LIMdomainonly2 PROM1 |prominin1 FLT1 |fmsrelated tyrosinekinase1 CDKN2C |cyclindependentkinaseinhibitor2C ZEB1 |zincfingerE−box bindinghomeobox 1 RARA |retinoicacidreceptoralpha metallopeptidase9 MMP9 |matrix CCND2 |cyclinD2 TGFBR2 |transforming growth factor betareceptor2 HHEX |hematopoieticallyexpressed homeobox factorERG |ERG,ETStranscription hsa05202 Cancer ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS Proteoglycans incancer available undera FZD3 | frizzled classreceptor 3 FZD3 |frizzled classreceptor 9 FZD9 |frizzled SDC1 |syndecan1 WNT16 |Wntfamily member16 subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory WNT5A |Wntfamily member5A TIAM1 |T−celllymphomainvasion andmetastasis1 SDC4 |syndecan4 WNT8B |Wntfamily member8B classreceptor10 FZD10 |frizzled BRAF |B−Rafproto−oncogene, kinase serine/threonine NANOG |Nanoghomeobox PRKACG |proteinkinasecAMP−activated catalyticsubunit gamma MAPK13 |mitogen−activated proteinkinase13 proteinS6kinaseB2 RPS6KB2 |ribosomal CAV3 |caveolin 3 12B IL12B |interleukin KRAS |proto−oncogene, GTPase WNT1 |Wntfamily member1 PRKCG |proteinkinaseCgamma WNT9B |Wntfamily member9B PDCD4 |programmed celldeath4 ERBB2 |erb−b2receptortyrosinekinase2 ACTG1 |actingamma1 TFAP4 factor |transcription AP−4 subunitITGA2 |integrin alpha2 PLAU |plasminogenactivator, urokinase MAPK12 |mitogen−activated proteinkinase12 MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 PRKACB |proteinkinasecAMP−activated catalyticsubunit beta PDPK1 |3−phosphoinositidedependentproteinkinase1 WNT4 |Wntfamily member4 MDM2 |proto−oncogene TNF |tumornecrosisfactor MAPK14 |mitogen−activated proteinkinase14 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha PTCH1 |patched1 ARHGEF12 |Rhoguaninenucleotide exchange factor 12 PLCE1 |phospholipaseCepsilon1 SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 1 ANK1 |ankyrin TWIST1 |twistfamily factor bHLH transcription 1 GPC1 |glypican1 STAT3 |signaltransducer andactivator 3 oftranscription 3 ANK3 |ankyrin MAPK1 |mitogen−activated proteinkinase1 HPSE |heparanase TLR2 |tolllike receptor2 CBL |Cbl proto−oncogene PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma ARAF |A−Rafproto−oncogene, kinase serine/threonine growth factorEGFR |epidermal receptor RAC1 |Racfamily smallGTPase 1 THBS1 |thrombospondin1 RHOA |ras homologfamily memberA WNT2 |Wntfamily member2 PPP1CA |proteinphosphatase1catalyticsubunit alpha SRC |proto−oncogene, non−receptortyrosinekinase CDC42 |celldivisioncycle42 GAB1 |GRB2associatedbindingprotein1 familySLC9A1 |solutecarrier 9memberA1 WNT10A |Wntfamily member10A subunitITGB3 |integrin beta3 MET |proto−oncogene, receptortyrosinekinase subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory IQGAP1 |IQmotifcontainingGTPase activating protein1 receptortype1 ITPR1 |inositol1,4,5−trisphosphate HCLS1 |hematopoieticcell−specificLyn substrate 1 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta subunit 12A PPP1R12A |proteinphosphatase1regulatory FAS |Fas cellsurface deathreceptor NRAS |proto−oncogene, GTPase ROCK1 |Rhoassociated coiled−coilcontainingproteinkinase1 FLNB |filaminB HOXD10 |homeobox D10 MAPK11 |mitogen−activated proteinkinase11 WNT2B |Wntfamily member2B subunitITGB5 |integrin beta5 COL21A1 |collagentypeXXIalpha1chain CTSL |cathepsinL ACTB |actinbeta VEGFA |vascular endothelialgrowth factor A PTPN6 |proteintyrosinephosphatase, non−receptortype6 SDC2 |syndecan2 PAK1 |p21(RAC1) activated kinase1 CAMK2G |calcium/calmodulindependentproteinkinaseIIgamma WNT9A |Wntfamily member9A HIF1A |hypoxia inducible factor 1alphasubunit subunit 12C PPP1R12C |proteinphosphatase1regulatory PLAUR |plasminogenactivator, urokinasereceptor PLCG2 |phospholipaseCgamma2 TGFB2 |transforming growth factor beta2 GRB2 |growth factor receptorboundprotein2 CTNNB1 |cateninbeta1 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta ROCK2 |Rhoassociated coiled−coilcontainingproteinkinase2 receptortype3 ITPR3 |inositol1,4,5−trisphosphate CD63 |molecule FN1 |fibronectin1 classreceptor7 FZD7 |frizzled MAPK3 |mitogen−activated proteinkinase3 CD44 |molecule(Indianblood group) PXN |paxillin PRKCB |proteinkinaseCbeta metallopeptidase2 MMP2 |matrix domainreceptor KDR |kinaseinsert classreceptor5 FZD5 |frizzled TWIST2 |twistfamily factor bHLHtranscription 2 metallopeptidase9 MMP9 |matrix MSN |moesin TGFB1 |transforming growth factor beta1 LUM |lumican GPC3 |glypican3 CAV2 |caveolin 2 RRAS |RASrelated FLNA |filaminA subunitITGA5 |integrin alpha5 hsa05205 Cancer ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 8 and Histogram 1501 0 −1.5 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Renal cellcarcinoma PIK3R2 | phosphoinositide−3−kinase regulatory subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory ELOB |elonginB ELOC |elonginC kinase BRAF |B−Rafproto−oncogene, serine/threonine KRAS |proto−oncogene, GTPase VHL |von Hippel−Lindautumor suppressor MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 CREBBP |CREBbindingprotein PAK3 |p21(RAC1) activated kinase3 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha RBX1 |ring−box 1 SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 EGLN1 |egl−9family hypoxia inducible factor 1 MAPK1 |mitogen−activated proteinkinase1 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit gamma kinase ARAF |A−Rafproto−oncogene, serine/threonine hydrocarbonARNT |aryl receptornuclear translocator PAK2 |p21(RAC1) activated kinase2 RAC1 |Racfamily smallGTPase 1 EP300 |E1Abindingproteinp300 FLCN |folliculin CDC42 |celldivisioncycle42 GAB1 |GRB2associatedbindingprotein1 EGLN3 |egl−9family hypoxia inducible factor 3 EGLN2 |egl−9family hypoxia inducible factor 2 MET |proto−oncogene, receptortyrosinekinase TGFB3 |transforming growth factor beta3 CRK |proto−oncogene, adaptorprotein subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory familySLC2A1 |solutecarrier 2member 1 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta NRAS |proto−oncogene, GTPase hydrocarbonARNT2 |aryl receptornuclear translocator 2 VEGFA | vascular endothelialgrowth factor A PAK1 |p21(RAC1) activated kinase1 HIF1A |hypoxia inducible factor 1alphasubunit RAP1A |RAP1A,memberofRASoncogenefamily TGFB2 |transforming growth factor beta2 GRB2 |growth factor receptorboundprotein2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta TGFA |transforming growth factor alpha MAPK3 |mitogen−activated proteinkinase3 PDGFB |plateletderived growth factor subunit B TGFB1 |transforming growth factor beta1 EPAS1 |endothelialPAS domainprotein1 hsa05211 Cancer ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Pancreatic cancer RAC3 |Racfamily smallGTPase 3 subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory BRCA2 |BRCA2,DNArepairassociated kinase BRAF |B−Rafproto−oncogene, serine/threonine KRAS |proto−oncogene, GTPase ERBB2 |erb−b2receptortyrosinekinase2 growth factorEGF |epidermal MAP2K1 |mitogen−activated proteinkinase1 factorE2F3 |E2Ftranscription 3 factorE2F2 |E2Ftranscription 2 SMAD4 |SMADfamily member4 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha PLD1 |phospholipaseD1 BAD |BCL2associatedagonistofcelldeath STAT3 |signaltransducer andactivator 3 oftranscription MAPK1 |mitogen−activated proteinkinase1 IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma factorE2F1 |E2Ftranscription 1 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit gamma kinase ARAF |A−Rafproto−oncogene, serine/threonine BCL2L1 |BCL2like 1 growth factorEGFR |epidermal receptor RAC1 |Racfamily smallGTPase 1 helix−loop−helixubiquitouskinase CHUK |conserved RELA |proto−oncogene, NF−kBsubunit TGFBR1 |transforming growth factor betareceptor1 RALBP1 |ralA bindingprotein1 CDC42 |celldivisioncycle42 TGFB3 |transforming growth factor beta3 CDKN2A |cyclindependentkinaseinhibitor2A subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta JAK1 |Janus kinase1 NFKB1 |nuclear factor kappaBsubunit 1 RAD51 |recombinase VEGFA | vascular endothelialgrowth factor A corepressor 1 RB1 |RBtranscriptional RALB |RASlike proto−oncogeneB TGFB2 |transforming growth factor beta2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta TGFA |transforming growth factor alpha STAT1 |signaltransducer andactivator 1 oftranscription MAPK3 |mitogen−activated proteinkinase3 TGFBR2 |transforming growth factor betareceptor2 TGFB1 |transforming growth factor beta1 RAC2 |Racfamily smallGTPase 2 hsa05212 Cancer ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS available undera CALML3 |calmodulinlike 3 subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory kinase BRAF |B−Rafproto−oncogene, serine/threonine KRAS |proto−oncogene, GTPase PRKCG |proteinkinaseCgamma SHC4 |SHCadaptorprotein4 SHC2 |SHCadaptorprotein2 growth factorEGF |epidermal MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 factorE2F3 |E2Ftranscription 3 SHC3 |SHCadaptorprotein3 factorE2F2 |E2Ftranscription 2 MDM2 |proto−oncogene PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 MAPK1 |mitogen−activated proteinkinase1 factorE2F1 |E2Ftranscription 1 PTEN |phosphataseandtensinhomolog PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma kinase ARAF |A−Rafproto−oncogene, serine/threonine growth factorEGFR |epidermal receptor CDKN2A |cyclindependentkinaseinhibitor2A subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta NRAS |proto−oncogene, GTPase corepressor1 RB1 |RBtranscriptional CAMK2G |calcium/calmodulindependentproteinkinaseIIgamma PLCG2 |phospholipaseCgamma2 GRB2 |growth factor receptorboundprotein2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta TGFA |transforming growth factor alpha SHC1 |SHCadaptorprotein1 MAPK3 |mitogen−activated proteinkinase3 PRKCB |proteinkinaseCbeta PDGFB |plateletderived growth factor subunit B hsa05214 Cancer ; this versionpostedFebruary19,2020. Glioma CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Prostate cancer PIK3R2 | phosphoinositide−3−kinase regulatory subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory kinase BRAF |B−Rafproto−oncogene, serine/threonine KRAS |proto−oncogene, GTPase CCNE2 |cyclinE2 ERBB2 |erb−b2receptortyrosinekinase2 PDGFC |plateletderived growth factor C growth factorEGF |epidermal MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 factorE2F3 |E2Ftranscription 3 CREBBP |CREBbindingprotein PDPK1 |3−phosphoinositidedependentproteinkinase1 GSK3B |glycogensynthasekinase3beta factorE2F2 |E2Ftranscription 2 MDM2 |proto−oncogene CREB5 |cAMPresponsive elementbindingprotein5 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha CDK2 |cyclindependentkinase2 CCNE1 |cyclinE1 BAD |BCL2associatedagonistofcelldeath SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 MAPK1 |mitogen−activated proteinkinase1 FOXO1 |forkhead box O1 IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma factorE2F1 |E2Ftranscription 1 PTEN |phosphataseandtensinhomolog PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma kinase ARAF |A−Rafproto−oncogene, serine/threonine growth factorEGFR |epidermal receptor helix−loop−helixubiquitouskinase CHUK |conserved EP300 |E1Abindingproteinp300 RELA |proto−oncogene, NF−kBsubunit CREB3L2 |cAMPresponsive elementbindingprotein3like 2 CREB3 |cAMPresponsive elementbindingprotein 3 subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta NRAS |proto−oncogene, GTPase NFKB1 |nuclear factor kappaBsubunit 1 corepressor 1 RB1 |RBtranscriptional factorTCF7L2 |transcription 7like 2 GRB2 |growth factor receptorboundprotein2 CTNNB1 |cateninbeta1 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta BCL2 |BCL2,apoptosisregulator TGFA |transforming growth factor alpha MAPK3 |mitogen−activated proteinkinase3 NFKBIA |NFKBinhibitoralpha PDGFB |plateletderived growth factor subunit B factorTCF7L1 |transcription 7like 1 hsa05215 Cancer ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS available undera PIK3R2 | phosphoinositide−3−kinase regulatory subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory FGF5 |fibroblast growth factor 5 kinase BRAF |B−Rafproto−oncogene, serine/threonine FGF4 |fibroblast growth factor 4 FGF6 |fibroblast growth factor 6 FGF17 |fibroblast growth factor 17 FGF20 |fibroblast growth factor 20 FGF22 |fibroblast growth factor 22 FGF14 |fibroblast growth factor 14 KRAS |proto−oncogene, GTPase FGF19 |fibroblast growth factor 19 FGF11 |fibroblast growth factor 11 PDGFC |plateletderived growth factor C growth factorEGF |epidermal FGF12 |fibroblast growth factor 12 MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 FGF9 |fibroblast growth factor 9 factorE2F3 |E2Ftranscription 3 factorE2F2 |E2Ftranscription 2 MDM2 |proto−oncogene FGF1 |fibroblast growth factor 1 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha BAD |BCL2associatedagonistofcelldeath MAPK1 |mitogen−activated proteinkinase1 factorE2F1 |E2Ftranscription 1 PTEN |phosphataseandtensinhomolog PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma kinase ARAF |A−Rafproto−oncogene, serine/threonine growth factorEGFR |epidermal receptor MET |proto−oncogene, receptortyrosinekinase CDKN2A |cyclindependentkinaseinhibitor2A subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta NRAS |proto−oncogene, GTPase corepressor 1 RB1 |RBtranscriptional PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta MAPK3 |mitogen−activated proteinkinase3 PDGFB |plateletderived growth factor subunit B Melanoma hsa05218 Cancer ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS Acute myeloid leukemia available undera EIF4EBP1 | eukaryotic translation initiationfactorEIF4EBP1 |eukaryotic 4Ebindingprotein1 subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory kinase BRAF |B−Rafproto−oncogene, serine/threonine proteinS6kinaseB2 RPS6KB2 |ribosomal KRAS |proto−oncogene, GTPase CCNA1 |cyclinA1 MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 FLT3 |fmsrelatedtyrosinekinase3 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha KIT |proto−oncogenereceptortyrosinekinase BAD |BCL2associatedagonistofcelldeath SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 STAT3 |signaltransducer andactivator 3 oftranscription MAPK1 |mitogen−activated proteinkinase1 IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit gamma kinase ARAF |A−Rafproto−oncogene, serine/threonine helix−loop−helixubiquitouskinase CHUK |conserved RELA |proto−oncogene, NF−kBsubunit subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta NRAS |proto−oncogene, GTPase STAT5B |signaltransducer andactivator 5B oftranscription NFKB1 |nuclear factor kappaBsubunit 1 CEBPA |CCAAT/enhancer bindingproteinalpha factorTCF7L2 |transcription 7like 2 SPI1 |Spi−1proto−oncogene GRB2 |growth factor receptorboundprotein2 PML |promyelocytic leukemia PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta STAT5A |signaltransducer andactivator 5A oftranscription MAPK3 |mitogen−activated proteinkinase3 RARA |retinoicacidreceptoralpha factorTCF7L1 |transcription 7like 1 hsa05221 Cancer ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC Non−small celllungcancer SS available undera FHIT |fragile histidinetriad subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory ALK |receptortyrosinekinase kinase BRAF |B−Rafproto−oncogene, serine/threonine KRAS |proto−oncogene, GTPase PRKCG |proteinkinaseCgamma ERBB2 |erb−b2receptortyrosinekinase2 microtubule associatedproteinlikeEML4 |echinoderm 4 growth factorEGF |epidermal MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 factorE2F3 |E2Ftranscription 3 PDPK1 |3−phosphoinositidedependentproteinkinase1 factorE2F2 |E2Ftranscription 2 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha BAD |BCL2associatedagonistofcelldeath SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 RXRB |retinoidXreceptorbeta FOXO3 |forkhead box O3 MAPK1 |mitogen−activated proteinkinase1 factorE2F1 |E2Ftranscription 1 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma kinase ARAF |A−Rafproto−oncogene, serine/threonine growth factorEGFR |epidermal receptor RXRG |retinoidXreceptorgamma RASSF5 |Rasassociationdomainfamily member5 CDKN2A |cyclindependentkinaseinhibitor2A kinase4 STK4 |serine/threonine subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta NRAS |proto−oncogene, GTPase corepressor 1 RB1 |RBtranscriptional PLCG2 |phospholipaseCgamma2 GRB2 |growth factor receptorboundprotein2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta TGFA |transforming growth factor alpha MAPK3 |mitogen−activated proteinkinase3 PRKCB |proteinkinaseCbeta hsa05223 Cancer ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243
SLC Central carbonmetabolismincancer
SS available undera SLC7A5 | solute carrier familySLC7A5 |solutecarrier 7member 5 GLS2 |glutaminase2 PDHB |pyruvate dehydrogenase E1betasubunit PDHA1 |pyruvate dehydrogenase E1alpha1subunit subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory IDH1 |isocitrate dehydrogenase (NADP(+))1,cytosolic KRAS |proto−oncogene, GTPase LDHA |lactatedehydrogenase A ERBB2 |erb−b2receptortyrosinekinase2 3 SIRT3 |sirtuin PFKM |phosphofructokinase, muscle NTRK3 |neurotrophicreceptortyrosinekinase3 MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 PGAM1 |phosphoglycerate mutase 1 FLT3 |fmsrelatedtyrosinekinase3 SCO2 |SCO2,cytochromecoxidase assembly protein PKM |pyruvate kinaseM1/2 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha KIT |proto−oncogenereceptortyrosinekinase HK3 |hexokinase 3 FGFR3 |fibroblast growth factor receptor3 MAPK1 |mitogen−activated proteinkinase1 phosphatase TIGAR |TP53inducedglycolysisregulatory G6PD |glucose−6−phosphatedehydrogenase PTEN |phosphataseandtensinhomolog PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma 6 SIRT6 |sirtuin growth factorEGFR |epidermal receptor MET |proto−oncogene, receptortyrosinekinase subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory HK2 |hexokinase 2 familySLC2A1 |solutecarrier 2member 1 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta NRAS |proto−oncogene, GTPase familySLC16A3 |solutecarrier 16member3 familySLC1A5 |solutecarrier 1member 5 HIF1A |hypoxia inducible factor 1alphasubunit PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta MAPK3 |mitogen−activated proteinkinase3 HKDC1 |hexokinase domaincontaining1 hsa05230 Cancer ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC Choline metabolismincancer SS available undera RAC3 |Racfamily smallGTPase 3 LYPLA1 |lysophospholipaseI translation initiationfactorEIF4EBP1 |eukaryotic 4Ebindingprotein1 subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory TSC2 |TSCcomplex subunit 2 proteinS6kinaseB2 RPS6KB2 |ribosomal KRAS |proto−oncogene, GTPase PRKCG |proteinkinaseCgamma PCYT1B |phosphatecytidylyltransferase 1,choline, beta PDGFC |plateletderived growth factor C WASF1 |WAS proteinfamily member1 DGKI |diacylglycerolkinaseiota familySLC22A5 |solutecarrier 22member5 WASL |Wiskott−Aldrich syndromelike growth factorEGF |epidermal MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 PDPK1 |3−phosphoinositidedependentproteinkinase1 DGKG |diacylglycerolkinasegamma PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha PIP5K1A |phosphatidylinositol−4−phosphate5−kinasetype1alpha PLD1 |phospholipaseD1 SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 PLD2 |phospholipaseD2 MAPK1 |mitogen−activated proteinkinase1 factorSP1 |Sp1transcription PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma DGKH |diacylglycerolkinaseeta growth factorEGFR |epidermal receptor RAC1 |Racfamily smallGTPase 1 RHEB |Rashomolog,mTORC1 binding familySLC44A5 |solutecarrier 44member5 PCYT1A |phosphatecytidylyltransferase 1,choline, alpha GPCPD1 |glycerophosphocholinephosphodiesterase 1 familySLC44A3 |solutecarrier 44member3 subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta WAS |Wiskott−Aldrich syndrome WASF2 |WAS proteinfamily member2 NRAS |proto−oncogene, GTPase CHKA |cholinekinasealpha HIF1A |hypoxia inducible factor 1alphasubunit GRB2 |growth factor receptorboundprotein2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta familySLC44A1 |solutecarrier 44member1 PLA2G4A |phospholipaseA2groupIVA PIP5K1B |phosphatidylinositol−4−phosphate5−kinasetype1beta MAPK3 |mitogen−activated proteinkinase3 familySLC22A4 |solutecarrier 22member4 PRKCB |proteinkinaseCbeta PDGFB |plateletderived growth factor subunit B familySLC44A4 |solutecarrier 44member4 RAC2 |Racfamily smallGTPase 2 hsa05231 Cancer ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC Carbohydrate metabolism Glycolysis /Gluconeogenesis SS available undera ENO3 |enolase3 ALDH3B2 |aldehyde dehydrogenase 3family memberB2 ADH1A |alcoholdehydrogenase 1A(classI),alpha polypeptide PDHB |pyruvate dehydrogenase E1betasubunit ALDH9A1 |aldehyde dehydrogenase 9family memberA1 PDHA1 |pyruvate dehydrogenase E1alpha1subunit GAPDHS |glyceraldehyde−3−phosphate dehydrogenase, spermatogenic GPI |glucose−6−phosphateisomerase PGK2 |phosphoglycerate kinase2 LDHAL6A |lactatedehydrogenase Alike 6A LDHA |lactatedehydrogenase A ALDH3A2 |aldehyde dehydrogenase 3family memberA2 ALDH1A3 |aldehyde dehydrogenase 1family memberA3 LDHAL6B |lactatedehydrogenase Alike 6B ALDH7A1 |aldehyde dehydrogenase 7family memberA1 PFKM |phosphofructokinase, muscle chainfamilyACSS1 member1 |acyl−CoAsynthetaseshort PGM2 |phosphoglucomutase 2 PGAM1 |phosphoglycerate mutase 1 ALDOC |aldolase,C fructose−bisphosphate isomerase 1 TPI1 |triosephosphate PGK1 |phosphoglycerate kinase 1 PKM |pyruvate kinaseM1/2 ALDOA |aldolase, A fructose−bisphosphate ENO1 |enolase1 HK3 |hexokinase 3 GAPDH |glyceraldehyde−3−phosphate dehydrogenase ADPGK |ADPdependentglucokinase BPGM |bisphosphoglycerate mutase G6PC3 |glucose−6−phosphatasecatalyticsubunit 3 ADH5 |alcoholdehydrogenase 5(classIII),chipolypeptide HK2 |hexokinase 2 ALDH3B1 |aldehyde dehydrogenase 3family memberB1 HKDC1 |hexokinase domaincontaining1 ADH1B |alcoholdehydrogenase 1B(classI),betapolypeptide hsa00010 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC Carbohydrate metabolism Pentose phosphatepathway SS available undera PGD |phosphogluconate dehydrogenase TALDO1 |transaldolase 1 GPI |glucose−6−phosphateisomerase TKTL2 |transketolase like 2 TKT |transketolase PFKM |phosphofructokinase, muscle PGM2 |phosphoglucomutase 2 DERA |deoxyribose−phosphate aldolase ALDOC |aldolase, C fructose−bisphosphate ALDOA A |aldolase, fructose−bisphosphate PGLS |6−phosphogluconolactonase H6PD |hexose−6−phosphate dehydrogenase/glucose 1−deh G6PD |glucose−6−phosphatedehydrogenase hsa00030 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC Carbohydrate metabolism SS Galactose metabolism available undera GALE |UDP−galactose−4−epimerase GALK1 |galactokinase1 LCT |lactase SI |sucrase−isomaltase musclePFKM |phosphofructokinase, PGM2 |phosphoglucomutase 2 GALT |galactose−1−phosphateuridylyltransferase MGAM |maltase−glucoamylase B4GALT1 |beta−1,4−galactosyltransferase 1 GLB1 |galactosidasebeta1 HK3 |hexokinase 3 GANC |glucosidasealpha,neutral C B4GALT2 |beta−1,4−galactosyltransferase 2 G6PC3 |glucose−6−phosphatasecatalyticsubunit 3 AKR1B10 |aldo−keto reductasefamily 1memberB10 GAA |glucosidasealpha,acid HK2 |hexokinase 2 GLA |galactosidasealpha HKDC1 |hexokinase domaincontaining1 hsa00052 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS Ovarian steroidogenesis available undera Endocrine system Endocrine CYP11A1 |cytochromeP450 family 11subfamily Amember 1 alphapolypeptide CGA |glycoproteinhormones, betapolypeptide LHB |luteinizinghormone PRKACG |protein kinasecAMP−activated catalytic subunit gamma CYP19A1 |cytochromeP450family 19subfamily Amember1 STAR protein |steroidogenicacuteregulatory HSD17B1 |hydroxysteroid 17−betadehydrogenase 1 PRKACB |proteinkinasecAMP−activated catalyticsubunit beta INSR |insulinreceptor SCARB1 |scavenger receptorclassBmember1 ADCY6 |adenylate cyclase6 ALOX5 |arachidonate 5−lipoxygenase PLA2G4A |phospholipaseA2groupIVA ADCY3 |adenylate cyclase3 ADCY4 |adenylate cyclase4 hsa04913 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS Insulin signalingpathway available undera Endocrine system Endocrine CALML3 |calmodulinlike 3 GYS2 |glycogensynthase2 subunit alpha1 kinaseregulatory PHKA1 |phosphorylase translation initiationfactorEIF4EBP1 |eukaryotic 4Ebindingprotein1 subunit 3E PPP1R3E |proteinphosphatase1regulatory subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory subunit 3D PPP1R3D |proteinphosphatase1regulatory IRS2 |insulinreceptorsubstrate 2 IRS4 |insulinreceptorsubstrate 4 BRAF |B−Rafproto−oncogene, kinase serine/threonine PRKACG |proteinkinasecAMP−activated catalyticsubunit gamma TSC2 |TSCcomplex subunit 2 PRKAB2 |proteinkinaseAMP−activated non−catalyticsubunit beta2 proteinS6kinaseB2 RPS6KB2 |ribosomal PRKAG2 |proteinkinaseAMP−activated non−catalyticsubunit gamma2 KRAS |proto−oncogene, GTPase PRKAB1 |proteinkinaseAMP−activated non−catalyticsubunit beta1 kinasecatalytic subunit gamma2 PHKG2 |phosphorylase PRKAG1 |proteinkinaseAMP−activated non−catalyticsubunit gamma1 INPPL1 |inositolpolyphosphatephosphataselike 1 SHC4 |SHCadaptorprotein4 L PYGL |glycogenphosphorylase ACACA |acetyl−CoAcarboxylase alpha SHC2 |SHCadaptorprotein2 subunit alpha2 kinase regulatory PHKA2 |phosphorylase MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 PRKACB |proteinkinasecAMP−activated catalyticsubunit beta SHC3 |SHCadaptorprotein3 EXOC7 |exocyst complex component7 kinasecatalytic subunit gamma1 PHKG1 |phosphorylase PDPK1 |3−phosphoinositidedependentproteinkinase1 GSK3B |glycogensynthasekinase3beta ACACB |acetyl−CoAcarboxylase beta subunit alpha PRKAR2A |proteinkinasecAMP−dependenttypeIIregulatory PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha BAD |BCL2associatedagonistofcelldeath SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 HK3 |hexokinase 3 MAPK1 |mitogen−activated proteinkinase1 CBL |Cbl proto−oncogene FOXO1 |forkhead box O1 GYS1 |glycogensynthase1 subunit beta PRKAR1B |proteinkinasecAMP−dependenttypeIregulatory sensitive type LIPE |lipaseE,hormone PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma subunit alpha PRKAR1A |proteinkinasecAMP−dependenttypeIregulatory ARAF |A−Rafproto−oncogene, kinase serine/threonine PDE3B |phosphodiesterase 3B G6PC3 |glucose−6−phosphatasecatalyticsubunit 3 RHEB |Rashomolog,mTORC1 binding translationEIF4E2 |eukaryotic initiationfactor 4Efamily member2 SH2B2 |SH2Badaptorprotein2 PPP1CA |proteinphosphatase1catalyticsubunit alpha FLOT2 |flotillin2 INSR |insulinreceptor PTPRF |proteintyrosinephosphatase, receptortypeF kinase1 MKNK1 |MAPkinaseinteracting serine/threonine CRK |proto−oncogene, adaptorprotein subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory HK2 |hexokinase 2 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta NRAS |proto−oncogene, GTPase PTPN1 |proteintyrosinephosphatase, non−receptortype1 INPP5K |inositolpolyphosphate−5−phosphataseK FLOT1 |flotillin1 PRKAA1 |proteinkinaseAMP−activated catalyticsubunit alpha1 SOCS1 |suppressorofcytokinesignaling1 RHOQ |ras homologfamily memberQ GRB2 |growth factor receptorboundprotein2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta subunit beta PRKAR2B |proteinkinasecAMP−dependenttypeIIregulatory SOCS2 |suppressorofcytokinesignaling2 TRIP10 |thyroid receptorinteractor 10 hormone SHC1 |SHCadaptorprotein1 MAPK3 |mitogen−activated proteinkinase3 HKDC1 |hexokinase domaincontaining1 hsa04910 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS GnRH signalingpathway available undera Endocrine system Endocrine CALML3 |calmodulinlike 3 2 GNRH2 |gonadotropinreleasing hormone alphapolypeptide CGA |glycoproteinhormones, betapolypeptide LHB |luteinizinghormone PRKACG |proteinkinasecAMP−activated catalyticsubunit gamma MAPK13 |mitogen−activated proteinkinase13 KRAS |proto−oncogene, GTPase CACNA1F |calciumvoltage−gated channelsubunit alpha1F CACNA1D |calciumvoltage−gated channelsubunit alpha1D PLCB4 |phospholipaseCbeta4 MAPK12 |mitogen−activated proteinkinase12 MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 PRKACB |proteinkinasecAMP−activated catalyticsubunit beta MAPK14 |mitogen−activated proteinkinase14 MAP3K1 |mitogen−activated proteinkinase 1 PRKCD |proteinkinaseCdelta PLD1 |phospholipaseD1 SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 PLD2 |phospholipaseD2 MAPK1 |mitogen−activated proteinkinase1 growth factorEGFR |epidermal receptor MAPK7 |mitogen−activated proteinkinase7 MAP3K2 |mitogen−activated proteinkinase2 GNAQ |Gproteinsubunit alpha q ADCY6 |adenylate cyclase6 SRC |proto−oncogene, non−receptortyrosinekinase CDC42 |celldivisioncycle42 PLCB2 |phospholipaseCbeta2 MAP2K6 |mitogen−activated proteinkinase6 MAP3K3 |mitogen−activated proteinkinase3 receptortype1 ITPR1 |inositol1,4,5−trisphosphate PTK2B |proteintyrosinekinase2beta metallopeptidase14 MMP14 |matrix NRAS |proto−oncogene, GTPase MAPK11 |mitogen−activated proteinkinase11 GNA11 |Gproteinsubunit alpha11 CAMK2G |calcium/calmodulindependentproteinkinaseIIgamma GRB2 |growth factor receptorboundprotein2 PLA2G4A |phospholipaseA2groupIVA receptortype3 ITPR3 |inositol1,4,5−trisphosphate MAPK3 |mitogen−activated proteinkinase3 ADCY3 |adenylate cyclase3 PRKCB |proteinkinaseCbeta metallopeptidase2 MMP2 |matrix ADCY4 |adenylate cyclase4 hsa04912 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: Progesterone−mediated oocyte maturation https://doi.org/10.1101/635243 SLC
SS available undera Endocrine system Endocrine MAD2L2 |mitoticarrestdeficient 2 like 2 ANAPC11 |anaphasepromoting complex subunit 11 CDC25A |celldivisioncycle25A subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory SPDYA |speedy/RINGOcellcycleregulatorfamily memberA kinase BRAF |B−Rafproto−oncogene, serine/threonine PRKACG |proteinkinasecAMP−activated catalyticsubunit gamma MAPK13 |mitogen−activated proteinkinase13 CCNB3 |cyclinB3 KRAS |proto−oncogene, GTPase ANAPC5 |anaphasepromotingcomplex subunit 5 CCNA1 |cyclinA1 MAPK12 |mitogen−activated proteinkinase12 MAP2K1 |mitogen−activated proteinkinase1 PRKACB |proteinkinasecAMP−activated catalyticsubunit beta GNAI3 |Gproteinsubunit alphai3 proteinS6kinaseA3 RPS6KA3 |ribosomal MAPK14 |mitogen−activated proteinkinase14 GNAI1 |Gproteinsubunit alphai1 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha CDK2 |cyclindependentkinase2 FZR1 |fizzyandcelldivisioncycle20related1 CDC25C |celldivisioncycle25C PKMYT1 |proteinkinase, membrane associatedtyrosine/threonine1 MAPK1 |mitogen−activated proteinkinase1 CDC26 |celldivisioncycle26 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma kinase ARAF |A−Rafproto−oncogene, serine/threonine PDE3B |phosphodiesterase 3B PLK1 |pololike kinase1 BUB1 kinase |BUB1 mitoticcheckpointserine/threonine CDC27 |celldivisioncycle27 ADCY6 |adenylate cyclase6 CCNB1 |cyclinB1 CDK1 |cyclindependentkinase1 subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta MAPK11 |mitogen−activated proteinkinase11 proteinS6kinaseA1 RPS6KA1 |ribosomal CCNB2 |cyclinB2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta CCNA2 |cyclinA2 GNAI2 |Gproteinsubunit alphai2 MAPK3 |mitogen−activated proteinkinase3 ADCY3 |adenylate cyclase3 ADCY4 |adenylate cyclase4 hsa04914 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC Prolactin signalingpathway SS available undera Endocrine system Endocrine PRLR |prolactinreceptor TH |tyrosinehydroxylase subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory alphapolypeptide CGA |glycoproteinhormones, betapolypeptide LHB |luteinizinghormone MAPK13 |mitogen−activated proteinkinase13 KRAS |proto−oncogene, GTPase SHC4 |SHCadaptorprotein4 SOCS6 |suppressorofcytokinesignaling6 TNFSF11 |TNFsuperfamily member 11 SHC2 |SHCadaptorprotein2 MAPK12 |mitogen−activated proteinkinase12 GALT |galactose−1−phosphateuridylyltransferase MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 SHC3 |SHCadaptorprotein3 GSK3B |glycogensynthasekinase3beta MAPK14 |mitogen−activated proteinkinase14 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 FOXO3 |forkhead box O3 STAT3 |signaltransducer andactivator 3 oftranscription MAPK1 |mitogen−activated proteinkinase1 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma RELA |proto−oncogene, NF−kBsubunit JAK2 |Janus kinase2 SRC |proto−oncogene, non−receptortyrosinekinase SOCS5 |suppressorofcytokinesignaling5 subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta NRAS |proto−oncogene, GTPase MAPK11 |mitogen−activated proteinkinase11 STAT5B |signaltransducer andactivator 5B oftranscription NFKB1 |nuclear factor kappaBsubunit 1 SOCS1 |suppressorofcytokinesignaling1 GRB2 |growth factor receptorboundprotein2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta TNFRSF11A |TNFreceptorsuperfamily member11a STAT1 |signaltransducer andactivator 1 oftranscription SOCS2 |suppressorofcytokinesignaling2 IRF1 |interferon factor regulatory 1 SHC1 |SHCadaptorprotein1 STAT5A |signaltransducer andactivator 5A oftranscription MAPK3 |mitogen−activated proteinkinase3 CCND2 |cyclinD2 hsa04917 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC Leukocyte transendothelialmigration
SS available undera Immune system CLDN9 |claudin9 CLDN14 |claudin14 subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory CLDN1 |claudin1 MAPK13 |mitogen−activated proteinkinase13 NOX3 |NADPHoxidase 3 MYL10 |myosin lightchain10 MYL7 |myosin lightchain7 ACTN3 |actininalpha3(gene/pseudogene) MYL2 |myosin lightchain2 PRKCG |proteinkinaseCgamma ACTG1 |actingamma1 CLDN6 |claudin6 CLDN2 |claudin2 MAPK12 |mitogen−activated proteinkinase12 NOX1 |NADPHoxidase 1 CLDN19 |claudin19 GNAI3 |Gproteinsubunit alphai3 CLDN18 |claudin18 CTNNA1 |cateninalpha1 MAPK14 |mitogen−activated proteinkinase14 GNAI1 |Gproteinsubunit alphai1 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma RAC1 |Racfamily smallGTPase 1 RHOA |ras homologfamily memberA CLDN3 |claudin3 CDC42 |celldivisioncycle42 RASSF5 |Rasassociationdomainfamily member5 BCAR1 |BCAR1,Casfamily scaffolding protein subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory MYL12A |myosin lightchain12A VAV1 |vav guaninenucleotide exchange factor 1 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta CLDN23 |claudin23 PTK2B |proteintyrosinekinase2beta RAPGEF3 |Rapguaninenucleotide exchange factor 3 ROCK1 |Rhoassociated coiled−coilcontainingproteinkinase1 MAPK11 |mitogen−activated proteinkinase11 ACTB |actinbeta SIPA1 |signal−inducedproliferation−associated 1 CLDN15 |claudin15 F11R |F11receptor subunitITGAM |integrin alphaM PLCG2 |phospholipaseCgamma2 RAP1A |RAP1A,memberofRASoncogenefamily ACTN4 |actininalpha4 MYL12B |myosin lightchain12B CTNNB1 |cateninbeta1 NCF2 |neutrophilcytosolicfactor 2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta NCF4 |neutrophilcytosolicfactor 4 ROCK2 |Rhoassociated coiled−coilcontainingproteinkinase2 VCAM1 |vascular celladhesionmolecule1 subunitITGB2 |integrin beta2 GNAI2 |Gproteinsubunit alphai2 CYBB |cytochromeb−245betachain PXN |paxillin VCL |vinculin VASP |vasodilator stimulated phosphoprotein PRKCB |proteinkinaseCbeta CYBA |cytochromeb−245alphachain metallopeptidase2 MMP2 |matrix ACTN1 |actininalpha1 metallopeptidase9 MMP9 |matrix ICAM1 |intercellularadhesionmolecule1 THY1 |Thy−1 cellsurface antigen CLDN4 |claudin4 CLDN7 |claudin7 MSN |moesin ESAM |endothelialcelladhesionmolecule CLDN5 |claudin5 RAC2 |Racfamily smallGTPase 2 MYL9 |myosin lightchain9 PECAM1 |plateletandendothelialcelladhesionmolecule1 hsa04670 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Immune system Platelet activation FGB | fibrinogen beta chain FGB |fibrinogen COL2A1 |collagentypeIIalpha1chain subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory MYLK2 |myosin lightchainkinase2 PRKACG |proteinkinasecAMP−activated catalyticsubunit gamma MAPK13 |mitogen−activated proteinkinase13 ACTG1 |actingamma1 PLCB4 |phospholipaseCbeta4 COL24A1 |collagentypeXXIValpha1chain subunitITGA2 |integrin alpha2 TBXAS1 |thromboxane A synthase1 STIM1 |stromalinteraction molecule1 MYLK4 |myosin lightchainkinasefamily member4 MAPK12 |mitogen−activated proteinkinase12 GP1BA |glycoproteinIbplateletalphasubunit PRKACB |proteinkinasecAMP−activated catalyticsubunit beta GNAI3 |Gproteinsubunit alphai3 MAPK14 |mitogen−activated proteinkinase14 GNAI1 |Gproteinsubunit alphai1 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha ARHGEF12 |Rhoguaninenucleotide exchange factor 12 GUCY1A2 |guanylate cyclase1soluble subunit alpha2 MAPK1 |mitogen−activated proteinkinase1 P2RY12 receptorP2Y12 |purinergic PRKG2 |proteinkinase, cGMP−dependent,typeII PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma RHOA |ras homologfamily memberA PPP1CA |proteinphosphatase1catalyticsubunit alpha GNAQ |Gproteinsubunit alphaq ADCY6 |adenylate cyclase6 SRC |proto−oncogene, non−receptortyrosinekinase PLCB2 |phospholipaseCbeta2 subunitITGB3 |integrin beta3 LYN |LYN proto−oncogene, Srcfamily tyrosinekinase subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory SNAP23 |synaptosomeassociatedprotein23 MYL12A |myosin lightchain12A receptortype1 ITPR1 |inositol1,4,5−trisphosphate PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta tyrosinekinase BTK |Bruton subunit 12A PPP1R12A |proteinphosphatase1regulatory ROCK1 |Rhoassociated coiled−coilcontainingproteinkinase1 SYK |spleenassociatedtyrosinekinase MAPK11 |mitogen−activated proteinkinase11 F2R |coagulationfactor IIthrombinreceptor ACTB |actinbeta receptor3 F2RL3 |F2Rlike thrombinortrypsin COL5A1 |collagentypeValpha1chain COL5A2 |collagentypeValpha2chain LCP2 |lymphocytecytosolicprotein2 RASGRP2 |RASguanyl releasingprotein2 COL5A3 |collagentypeValpha3chain PLCG2 |phospholipaseCgamma2 RAP1A |RAP1A,memberofRASoncogenefamily MYL12B |myosin lightchain12B PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta PLA2G4A |phospholipaseA2groupIVA receptorP2X1 P2RX1 |purinergic ROCK2 |Rhoassociated coiled−coilcontainingproteinkinase2 receptortype3 ITPR3 |inositol1,4,5−trisphosphate GUCY1B3 |guanylate cyclase1soluble subunit beta FCER1G |Fcfragment ofIgEreceptorIg TLN2 |talin2 PRKG1 |proteinkinase, cGMP−dependent,typeI GNA13 |Gproteinsubunit alpha13 FERMT3 |fermitin family member3 COL27A1 |collagentypeXXVIIalpha1chain GNAI2 |Gproteinsubunit alphai2 MAPK3 |mitogen−activated proteinkinase3 ADCY3 |adenylate cyclase3 VASP |vasodilator stimulated phosphoprotein TLN1 |talin1 APBB1IP |amyloid betaprecursorproteinbindingfamily Bmember1interacting protein COL3A1 |collagentypeIIIalpha1chain COL1A1 |collagentypeIalpha1chain VWF |von Willebrand factor ADCY4 |adenylate cyclase4 COL1A2 |collagentypeIalpha2chain hsa04611 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 4 and Histogram 1501 0 −1.5 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243
SLC processingAntigen andpresentation
SS available undera Immune system HSPA6 |heatshockproteinfamily A(Hsp70)member6 CTSB |cathepsinB KIR2DL4 |killercellimmunoglobulin like receptor, two Igdomainsandlongcytoplasmic tail4 NFYC |nuclear factor transcription Ysubunit gamma IFI30 |IFI30,lysosomalthiolreductase HSPA5 |heatshockproteinfamily A(Hsp70)member5 HSPA1L |heatshockproteinfamily A(Hsp70)member1like TNF |tumornecrosisfactor CALR |calreticulin factor containingprotein RFXANK |regulatory Xassociatedankyrin CANX |calnexin PSME3 |proteasomeactivator subunit 3 HLA−G |majorhistocompatibilitycomplex, classI,G CTSL |cathepsinL TAPBP |TAP bindingprotein B2M |beta−2−microglobulin TAP2 2,ATP |transporter bindingcassettesubfamily Bmember HLA−C |majorhistocompatibilitycomplex, classI,C TAP1 1,ATP |transporter bindingcassettesubfamily Bmember HLA−E |majorhistocompatibilitycomplex, classI,E HLA−F |majorhistocompatibilitycomplex, classI,F HLA−B |majorhistocompatibilitycomplex, classI,B hsa04612 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243
SLC Toll−like receptorsignalingpathway
SS available undera Immune system PIK3R2 | phosphoinositide−3−kinase regulatory subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory bindingprotein LBP |lipopolysaccharide IFNB1 |interferon beta1 MAPK13 |mitogen−activated proteinkinase13 IFNA21 |interferon alpha21 IFNA5 |interferon alpha5 IKBKE |inhibitorofnuclear factor kappaBkinasesubunit epsilon TLR9 |tolllike receptor9 1receptorassociatedkinase4 IRAK4 |interleukin MYD88 |myeloid response88 differentiation primary 12B IL12B |interleukin 12A IL12A |interleukin TIRAP |TIRdomaincontainingadaptorprotein TBK1 |TANK binding kinase1 MAPK12 |mitogen−activated proteinkinase12 MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 TLR8 |tolllike receptor8 TNF |tumornecrosisfactor TLR6 |tolllike receptor6 MAPK14 |mitogen−activated proteinkinase14 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha CD80 |molecule IFNAR1 |interferon alphaandbetareceptorsubunit 1 FADD |Fas associatedviadeathdomain MAPK1 |mitogen−activated proteinkinase1 TLR2 |tolllike receptor2 IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma TLR1 |tolllike receptor1 RAC1 |Racfamily smallGTPase 1 IRF3 |interferon factor regulatory 3 helix−loop−helixubiquitouskinase CHUK |conserved RELA |proto−oncogene, NF−kBsubunit CASP8 |caspase8 TICAM1 |tolllike receptoradaptormolecule1 MAP2K6 |mitogen−activated proteinkinase6 IFNAR2 |interferon alphaandbetareceptorsubunit 2 1beta IL1B |interleukin subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta kinase1 RIPK1 |receptorinteracting serine/threonine MAPK11 |mitogen−activated proteinkinase11 IRF7 |interferon factor regulatory 7 TLR3 |tolllike receptor3 NFKB1 |nuclear factor kappaBsubunit 1 SPP1 |secretedphosphoprotein1 CD14 |molecule PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta STAT1 |signaltransducer andactivator 1 oftranscription LY96 |lymphocyteantigen96 MAPK3 |mitogen−activated proteinkinase3 MAP3K8 |mitogen−activated proteinkinase8 NFKBIA |NFKBinhibitoralpha CTSK |cathepsinK CXCL9 |C−X−Cmotifchemokineligand9 hsa04620 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 15and Histogram Color Key 101 0 −1 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 RIG−I−like receptorsignalingpathway SLC
SS available undera Immune system IFNK |interferon kappa IFNB1 |interferon beta1 MAPK13 |mitogen−activated proteinkinase13 IFNW1 |interferon omega1 IFNA21 |interferon alpha21 IFNA5 |interferon alpha5 IKBKE |inhibitorofnuclear factor kappaBkinasesubunit epsilon 12B IL12B |interleukin IFNE |interferon epsilon 12A IL12A |interleukin TBK1 |TANK binding kinase1 MAPK12 |mitogen−activated proteinkinase12 MAVS antiviral signalingprotein |mitochondrial TNF |tumornecrosisfactor MAPK14 |mitogen−activated proteinkinase14 MAP3K1 |mitogen−activated proteinkinase 1 SIKE1 |suppressorofIKBKE1 OTUD5 |OTU deubiquitinase5 DDX3X |DEAD−box helicase3,X−linked FADD |Fas associated viadeathdomain IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma PIN1 |peptidylprolylcis/trans isomerase, NIMA−interacting 1 IRF3 |interferon factor regulatory 3 ATG12 |autophagyrelated12 helix−loop−helixubiquitouskinase CHUK |conserved fingerprotein125 RNF125 |ring RELA |proto−oncogene, NF−kBsubunit CASP8 |caspase8 TANK |TRAFfamily memberassociatedNFKBactivator NFKBIB |NFKBinhibitorbeta kinase1 RIPK1 |receptorinteracting serine/threonine MAPK11 |mitogen−activated proteinkinase11 IRF7 |interferon factor regulatory 7 NFKB1 |nuclear factor kappaBsubunit 1 motifcontaining25 TRIM25 |tripartite ISG15 |ubiquitin−like modifier CASP10 |caspase10 NFKBIA |NFKBinhibitoralpha TMEM173 |transmembrane protein173 hsa04622 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 6 and Histogram 1501 0 −1.5 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC Fc epsilonRIsignalingpathway
SS available undera Immune system RAC3 |Racfamily smallGTPase 3 subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory MAPK13 |mitogen−activated proteinkinase13 5 IL5 |interleukin 3 IL3 |interleukin KRAS |proto−oncogene, GTPase MAPK12 |mitogen−activated proteinkinase12 MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 PDPK1 |3−phosphoinositidedependentproteinkinase1 TNF |tumornecrosisfactor MAPK14 |mitogen−activated proteinkinase14 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha PRKCD |proteinkinaseCdelta SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 MAPK1 |mitogen−activated proteinkinase1 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit gamma RAC1 |Racfamily smallGTPase 1 MAP2K6 |mitogen−activated proteinkinase6 LYN |LYN proto−oncogene, Srcfamily tyrosinekinase subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory VAV1 |vav guaninenucleotide exchange factor 1 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta tyrosinekinase BTK |Bruton NRAS |proto−oncogene, GTPase SYK |spleenassociatedtyrosinekinase MAPK11 |mitogen−activated proteinkinase11 MS4A2 |membrane spanning4−domainsA2 LCP2 |lymphocytecytosolicprotein2 GAB2 |GRB2associatedbindingprotein2 PLCG2 |phospholipaseCgamma2 FCER1A |Fcfragment ofIgEreceptorIa GRB2 |growth factor receptorboundprotein2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta PLA2G4A |phospholipaseA2groupIVA INPP5D |inositolpolyphosphate−5−phosphataseD FCER1G |Fcfragment ofIgEreceptorIg MAPK3 |mitogen−activated proteinkinase3 PRKCB |proteinkinaseCbeta RAC2 |Racfamily smallGTPase 2 hsa04664 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 15and Histogram 1501 0 −1.5 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243
SLC Fc gammaR−mediatedphagocytosis
SS available undera Immune system SCIN |scinderin SPHK1 |sphingosinekinase1 subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory factorARF6 |ADPribosylation 6 MYO10 |myosin X proteinS6kinaseB2 RPS6KB2 |ribosomal FCGR2B |Fcfragment ofIgGreceptorIIb PRKCG |proteinkinaseCgamma INPPL1 |inositolpolyphosphatephosphataselike 1 WASF1 |WAS proteinfamily member1 WASL |Wiskott−Aldrich syndromelike MAP2K1 |mitogen−activated proteinkinase1 SPHK2 |sphingosinekinase2 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha PRKCD |proteinkinaseCdelta PIP5K1A |phosphatidylinositol−4−phosphate5−kinasetype1alpha FCGR1A |Fcfragment ofIgGreceptorIa PLD1 |phospholipaseD1 PLD2 |phospholipaseD2 LIMK1 |LIMdomainkinase1 ARPC2 |actinrelatedprotein2/3complex subunit 2 MAPK1 |mitogen−activated proteinkinase1 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit gamma RAC1 |Racfamily smallGTPase 1 DOCK2 |dedicatorofcytokinesis2 DNM2 |dynamin2 ARPC3 |actinrelatedprotein2/3complex subunit 3 CDC42 |celldivisioncycle42 CRK |proto−oncogene, adaptorprotein LYN |LYN proto−oncogene, Srcfamily tyrosinekinase subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory VAV1 |vav guaninenucleotide exchange factor 1 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta WAS |Wiskott−Aldrich syndrome WASF2 |WAS proteinfamily member2 SYK |spleenassociatedtyrosinekinase LIMK2 |LIMdomainkinase2 ARPC4 |actinrelatedprotein2/3complex subunit 4 CFL1 |cofilin1 ARPC1A |actinrelatedprotein2/3complex subunit 1A PAK1 |p21(RAC1) activated kinase1 GAB2 |GRB2associatedbindingprotein2 PLCG2 |phospholipaseCgamma2 MARCKS |myristoylated proteinkinaseCsubstrate alaninerich repeatandPHdomain1 ASAP1 |ArfGAPwithSH3domain,ankyrin HCK |proto−oncogene, Srcfamily tyrosinekinase CFL2 |cofilin2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta PLA2G4A |phospholipaseA2groupIVA INPP5D |inositolpolyphosphate−5−phosphataseD PIP5K1B |phosphatidylinositol−4−phosphate5−kinasetype1beta MAPK3 |mitogen−activated proteinkinase3 ARPC5 |actinrelatedprotein2/3complex subunit 5 PTPRC |proteintyrosinephosphatase, receptortypeC VASP |vasodilator stimulated phosphoprotein PRKCB |proteinkinaseCbeta ARPC1B |actinrelatedprotein2/3complex subunit 1B GSN |gelsolin RAC2 |Racfamily smallGTPase 2 hsa04666 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 8 and Histogram Color Key 101 0 −1 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243
SLC Bacterial invasion ofepithelialcells
SS available undera Infectious disease SEPT3 |septin3 MAD2L2 |mitoticarrestdeficient 2 like 2 ELMO3 |engulfmentandcellmotility3 subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory CLTCL1 heavy |clathrin chainlike 1 SEPT12 |septin12 CAV3 |caveolin 3 SEPT8 |septin8 ACTG1 |actingamma1 SHC4 |SHCadaptorprotein4 WASF1 |WAS proteinfamily member1 CLTA lightchainA |clathrin DNM3 |dynamin3 SHC2 |SHCadaptorprotein2 ARHGAP10 |RhoGTPase activating protein10 WASL |Wiskott−Aldrich syndromelike ELMO2 |engulfmentandcellmotility2 SHC3 |SHCadaptorprotein3 CTNNA1 |cateninalpha1 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha ARPC2 |actinrelatedprotein2/3complex subunit 2 CLTC heavy |clathrin chain CLTB lightchainB |clathrin CBL |Cbl proto−oncogene DNM1 |dynamin1 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit gamma RAC1 |Racfamily smallGTPase 1 RHOA |ras homologfamily memberA DNM2 |dynamin2 ARPC3 |actinrelatedprotein2/3complex subunit 3 SRC |proto−oncogene, non−receptortyrosinekinase CDC42 |celldivisioncycle42 GAB1 |GRB2associatedbindingprotein1 SEPT2 |septin2 MET |proto−oncogene, receptortyrosinekinase CRK |proto−oncogene, adaptorprotein BCAR1 |BCAR1,Casfamily scaffolding protein subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory HCLS1 |hematopoieticcell−specificLyn substrate 1 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta WAS |Wiskott−Aldrich syndrome WASF2 |WAS proteinfamily member2 ARPC4 |actinrelatedprotein2/3complex subunit 4 ACTB |actinbeta ARPC1A |actinrelatedprotein2/3complex subunit 1A DOCK1 |dedicatorofcytokinesis1 CTNNB1 |cateninbeta1 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta FN1 |fibronectin1 linkedILK |integrin kinase SHC1 |SHCadaptorprotein1 RHOG |ras homologfamily memberG ARPC5 |actinrelatedprotein2/3complex subunit 5 PXN |paxillin VCL |vinculin ARPC1B |actinrelatedprotein2/3complex subunit 1B CAV2 |caveolin 2 subunitITGA5 |integrin alpha5 hsa05100 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS Vibrio cholerae infection available undera Infectious disease ATP6V0E2 |ATPase V0 subunit e2 H+transporting ATP6V1C2 |ATPase V1subunit C2 H+transporting ERO1A |endoplasmicreticulumoxidoreductase 1alpha SEC61A2 |Sec61translocon alpha2 subunit ATP6V1F |ATPase V1subunit F H+transporting PRKACG |proteinkinasecAMP−activated catalyticsubunit gamma ATP6V1B1 |ATPase V1subunit B1 H+transporting PRKCG |proteinkinaseCgamma ACTG1 |actingamma1 ATP6V1H |ATPase V1subunit H H+transporting ATP6V1A |ATPase V1subunit A H+transporting SEC61A1 |Sec61translocon alpha1 subunit KDELR2 |KDELendoplasmicreticulumproteinretentionreceptor 2 PRKACB |proteinkinasecAMP−activated catalyticsubunit beta KDELR3 |KDELendoplasmicreticulumproteinretentionreceptor 3 factorARF1 |ADPribosylation 1 ATP6V0C |ATPase V0subunit c H+transporting ATP6AP1 |ATPase protein1 accessory H+transporting ATP6V0D1 |ATPase V0subunit d1 H+transporting ATP6V1B2 |ATPase V1subunit B2 H+transporting TJP2 |tightjunctionprotein2 ATP6V0E1 |ATPase V0subunit e1 H+transporting ATP6V0B |ATPase V0subunit b H+transporting ATP6V0A1 |ATPase V0subunit a1 H+transporting CFTR |cysticfibrosistransmembrane conductanceregulator KDELR1 |KDELendoplasmicreticulumproteinretentionreceptor1 ATP6V1E1 |ATPase V1subunit E1 H+transporting SEC61G |Sec61translocon gammasubunit ATP6V1C1 |ATPase V1subunit C1 H+transporting TCIRG1 |T−cellimmune regulator1,ATPase V0subunit a3 H+transporting ACTB |actinbeta PLCG2 |phospholipaseCgamma2 KCNQ1 |potassiumvoltage−gated channelsubfamily Qmember1 ADCY3 |adenylate cyclase3 PRKCB |proteinkinaseCbeta hsa05110 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 6 and Histogram Color Key 101 0 −1 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue Epithelial cellsignalinginHelicobacterpylori infection
CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Infectious disease ATP6V0E2 |ATPase V0 subunit e2 H+transporting ATP6V1C2 |ATPase V1subunit C2 H+transporting ATP6V1F |ATPase V1subunit F H+transporting MAPK13 |mitogen−activated proteinkinase13 ATP6V1B1 |ATPase V1subunit B1 H+transporting ATP6V1H |ATPase V1subunit H H+transporting ATP6V1A |ATPase V1subunit A H+transporting MAPK12 |mitogen−activated proteinkinase12 ATP6V0C |ATPase V0subunit c H+transporting ATP6AP1 |ATPase protein1 accessory H+transporting MAPK14 |mitogen−activated proteinkinase14 CXCR1 |C−X−Cmotifchemokinereceptor1 ATP6V0D1 |ATPase V0subunit d1 H+ transporting Srckinase CSK |C−terminal ADAM17 |ADAM metallopeptidasedomain17 ATP6V1B2 |ATPase V1subunit B2 H+transporting ATP6V0E1 |ATPase V0subunit e1 H+transporting IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma ATP6V0B |ATPase V0subunit b H+transporting ATP6V0A1 |ATPase V0subunit a1 H+transporting growth factorEGFR |epidermal receptor RAC1 |Racfamily smallGTPase 1 helix−loop−helixubiquitouskinase CHUK |conserved RELA |proto−oncogene, NF−kBsubunit SRC |proto−oncogene, non−receptortyrosinekinase CDC42 |celldivisioncycle42 ATP6V1E1 |ATPase V1subunit E1 H+transporting MET |proto−oncogene, receptortyrosinekinase LYN |LYN proto−oncogene, Srcfamily tyrosinekinase ATP6V1C1 |ATPase V1subunit C1 H+transporting TCIRG1 |T−cellimmune regulator1,ATPase V0subunit a3 H+transporting MAPK11 |mitogen−activated proteinkinase11 NFKB1 |nuclear factor kappaBsubunit 1 PAK1 |p21(RAC1) activated kinase1 F11R |F11receptor PLCG2 |phospholipaseCgamma2 ADAM10 |ADAM metallopeptidasedomain10 NFKBIA |NFKBinhibitoralpha CXCL1 |C−X−Cmotifchemokineligand1 hsa05120 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 8 and Histogram 1501 0 −1.5 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Infectious disease Salmonella infection PFN4 |profilinfamily member4 bindingprotein LBP |lipopolysaccharide MAPK13 |mitogen−activated proteinkinase13 1alpha IL1A |interleukin MYD88 |myeloid response88 differentiation primary DYNC1LI1 chain1 |dyneincytoplasmic1lightintermediate ACTG1 |actingamma1 WASF1 |WAS proteinfamily member1 WASL |Wiskott−Aldrich syndromelike MAPK12 |mitogen−activated proteinkinase12 NLRC4 |NLRfamily CARDdomaincontaining4 KLC1 |kinesinlightchain1 MAPK14 |mitogen−activated proteinkinase14 RILP |Rabinteracting lysosomalprotein ARPC2 |actinrelatedprotein2/3complex subunit 2 MAPK1 |mitogen−activated proteinkinase1 homologyandRUNPLEKHM2 |pleckstrin domaincontainingM2 DYNC2H1 |dyneincytoplasmic2heavy chain 1 RAC1 |Racfamily smallGTPase 1 oxideNOS2 |nitric synthase 2 RELA |proto−oncogene, NF−kBsubunit DYNC1H1 |dyneincytoplasmic1heavy chain 1 ARPC3 |actinrelatedprotein2/3complex subunit 3 CDC42 |celldivisioncycle42 IFNGR2 |interferon gammareceptor2 PKN1 |proteinkinaseN1 1beta IL1B |interleukin RAB7A |RAB7A,memberRASoncogenefamily DYNC1LI2 chain2 |dyneincytoplasmic1lightintermediate WAS |Wiskott−Aldrich syndrome WASF2 |WAS proteinfamily member2 ROCK1 |Rhoassociatedcoiled−coilcontainingproteinkinase1 FLNB |filaminB MAPK11 |mitogen−activated proteinkinase11 ARPC4 |actinrelatedprotein2/3complex subunit 4 RAB7B |RAB7B, memberRASoncogenefamily CXCL3 |C−X−Cmotifchemokineligand3 ACTB |actinbeta NFKB1 |nuclear factor kappaBsubunit 1 PKN2 |proteinkinaseN2 PFN1 |profilin1 ARPC1A |actinrelatedprotein2/3complex subunit 1A 18 IL18 |interleukin CD14 |molecule ROCK2 |Rhoassociatedcoiled−coilcontainingproteinkinase2 MYH9 |myosin heavy chain9 RHOG |ras homologfamily memberG MAPK3 |mitogen−activated proteinkinase3 PKN3 |proteinkinaseN3 ARPC5 |actinrelatedprotein2/3complex subunit 5 CASP1 |caspase1 MYH14 |myosin heavy chain14 ARPC1B |actinrelatedprotein2/3complex subunit 1B IFNGR1 |interferon gammareceptor1 CXCL1 |C−X−Cmotifchemokineligand1 PYCARD |PYDandCARDdomaincontaining FLNA |filaminA hsa05132 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 6 and Histogram Color Key 101 0 −1 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Infectious disease CALML3 |calmodulinlike 3 C4BPB |complementcomponent 4bindingproteinbeta MAPK13 |mitogen−activated proteinkinase13 1receptorassociatedkinase4 IRAK4 |interleukin 1alpha IL1A |interleukin MYD88 |myeloid response88 differentiation primary 12B IL12B |interleukin C4BPA |complementcomponent4bindingproteinalpha 12A IL12A |interleukin TIRAP |TIRdomaincontainingadaptorprotein MAPK12 |mitogen−activated proteinkinase12 GNAI3 |Gproteinsubunit alphai3 TNF |tumornecrosisfactor MAPK14 |mitogen−activated proteinkinase14 GNAI1 |Gproteinsubunit alphai1 MAPK1 |mitogen−activated proteinkinase1 IRF3 |interferon factor regulatory 3 RHOA |ras homologfamily memberA oxideNOS2 |nitric synthase 2 NLRP3 |NLRfamily pyrin domaincontaining3 RELA |proto−oncogene, NF−kBsubunit TICAM1 |tolllike receptoradaptormolecule 1 1beta IL1B |interleukin MAPK11 |mitogen−activated proteinkinase11 CFL1 |cofilin1 NFKB1 |nuclear factor kappaBsubunit 1 C1QC |complementC1qCchain subunitITGAM |integrin alphaM CD14 |molecule CXCL6 |C−X−Cmotifchemokineligand6 CFL2 |cofilin2 C1QB |complementC1qBchain C2 |complement LY96 |lymphocyteantigen96 IRF1 |interferon factor regulatory 1 subunitITGB2 |integrin beta2 C1R |complementC1r GNAI2 |Gproteinsubunit alphai2 C3 |complement MAPK3 |mitogen−activated proteinkinase3 C1QA |complementC1qAchain CASP1 |caspase1 C1S |complementC1s family Gmember1 SERPING1 |serpin PYCARD |PYDandCARDdomaincontaining subunitITGA5 |integrin alpha5 hsa05133 Pertussis ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 8 and Histogram Color Key 11 −1 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Infectious disease EEF1A2 | eukaryotic translationEEF1A2 |eukaryotic elongationfactor 1alpha2 BNIP3 |BCL2interacting protein3 HSPA6 |heatshockproteinfamily A(Hsp70) member6 HBS1L |HBS1like translational GTPase MYD88 |myeloid response 88 differentiation primary NAIP |NLRfamily protein apoptosisinhibitory 12B IL12B |interleukin 12A IL12A |interleukin BCL2L13 |BCL2like 13 SEC22B |SEC22homologB, vesicle trafficking protein (gene/pseudogene) NLRC4 |NLRfamily CARDdomaincontaining4 factorARF1 |ADPribosylation 1 VCP |valosin containingprotein HSPA1L |heatshockproteinfamily A(Hsp70) member1like TNF |tumornecrosisfactor RAB1B |RAB1B, memberRASoncogenefamily TLR2 |tolllike receptor2 SAR1A |secretionassociatedRasrelatedGTPase 1A factorHSF1 |heatshocktranscription 1 RELA |proto−oncogene, NF−kBsubunit RAB1A |RAB1A,memberRASoncogenefamily CASP8 |caspase8 APAF1 |apoptoticpeptidaseactivating factor 1 1beta IL1B |interleukin CXCL3 |C−X−Cmotifchemokineligand3 NFKB1 |nuclear factor kappaBsubunit 1 subunitITGAM |integrin alphaM 18 IL18 |interleukin CD14 |molecule subunitITGB2 |integrin beta2 NFKB2 |nuclear factor kappaBsubunit 2 C3 |complement CASP1 |caspase1 NFKBIA |NFKBinhibitoralpha CXCL1 |C−X−Cmotifchemokineligand1 PYCARD |PYDandCARDdomaincontaining Legionellosis hsa05134 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 15 and Histogram Color Key 11 −1 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue doi: CA Chagas disease(Americantrypanosomiasis) https://doi.org/10.1101/635243 SLC
SS available undera Infectious disease PPP2R2C | protein phosphatase 2 regulatory subunit Bgamma PPP2R2C |proteinphosphatase 2 regulatory GNA15 |Gproteinsubunit alpha15 subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory IFNB1 |interferon beta1 MAPK13 |mitogen−activated proteinkinase13 TLR9 |tolllike receptor9 1receptorassociatedkinase4 IRAK4 |interleukin MYD88 |myeloid response88 differentiation primary 12B IL12B |interleukin PLCB4 |phospholipaseCbeta4 12A IL12A |interleukin subunit Balpha PPP2R2A |proteinphosphatase2regulatory MAPK12 |mitogen−activated proteinkinase12 GNAI3 |Gproteinsubunit alphai3 TNF |tumornecrosisfactor CALR |calreticulin TLR6 |tolllike receptor6 MAPK14 |mitogen−activated proteinkinase14 GNAI1 |Gproteinsubunit alphai1 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha PPP2CA |proteinphosphatase2catalyticsubunit alpha FADD |Fas associatedviadeathdomain MAPK1 |mitogen−activated proteinkinase1 TLR2 |tolllike receptor2 IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit gamma helix−loop−helixubiquitouskinase CHUK |conserved oxideNOS2 |nitric synthase 2 RELA |proto−oncogene, NF−kBsubunit TGFBR1 |transforming growth factor betareceptor1 GNAQ |Gproteinsubunit alpha q CASP8 |caspase8 TICAM1 |tolllike receptoradaptormolecule1 PLCB2 |phospholipaseCbeta2 IFNGR2 |interferon gammareceptor2 1beta IL1B |interleukin TGFB3 |transforming growth factor beta3 PPP2CB |proteinphosphatase2catalyticsubunit beta subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta CFLAR |CASP8andFADD like apoptosisregulator FAS |Fas cellsurface deathreceptor TNFRSF1A |TNFreceptorsuperfamily member1A MAPK11 |mitogen−activated proteinkinase11 NFKB1 |nuclear factor kappaBsubunit 1 GNA11 |Gproteinsubunit alpha11 C1QC |complementC1qCchain TGFB2 |transforming growth factor beta2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta C1QB |complementC1qBchain GNAI2 |Gproteinsubunit alphai2 C3 |complement MAPK3 |mitogen−activated proteinkinase3 C1QA |complementC1qAchain ACE |angiotensinIconverting enzyme NFKBIA |NFKBinhibitoralpha IFNGR1 |interferon gammareceptor1 TGFBR2 |transforming growth factor betareceptor2 TGFB1 |transforming growth factor beta1 family Emember1 SERPINE1 |serpin hsa05142 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 30 and Histogram 302 0 −3 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Infectious disease COL2A1 |collagentypeIIalpha1 chain GNA15 |Gproteinsubunit alpha15 C8G |complementC8gammachain subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory LAMA1 |lamininsubunit alpha1 PRKACG |proteinkinasecAMP−activated catalyticsubunit gamma ACTN3 |actininalpha3(gene/pseudogene) RAB5A |RAB5A,memberRASoncogenefamily 12B IL12B |interleukin PRKCG |proteinkinaseCgamma PLCB4 |phospholipaseCbeta4 12A IL12A |interleukin COL24A1 |collagentypeXXIValpha1chain PRKACB |proteinkinasecAMP−activated catalyticsubunit beta TNF |tumornecrosisfactor PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha 1receptortype2 IL1R2 |interleukin TLR2 |tolllike receptor2 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit gamma oxideNOS2 |nitric synthase 2 RELA |proto−oncogene, NF−kBsubunit HSPB1 |heatshockproteinfamily B(small)member1 GNAQ |Gproteinsubunit alphaq PLCB2 |phospholipaseCbeta2 1beta IL1B |interleukin TGFB3 |transforming growth factor beta3 RAB7A |RAB7A,memberRASoncogenefamily subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit beta RAB7B |RAB7B, memberRASoncogenefamily NFKB1 |nuclear factor kappaBsubunit 1 GNA11 |Gproteinsubunit alpha11 family Bmember1 SERPINB1 |serpin COL5A1 |collagentypeValpha1chain COL5A2 |collagentypeValpha2chain subunitITGAM |integrin alphaM COL5A3 |collagentypeValpha3chain TGFB2 |transforming growth factor beta2 CD14 |molecule ACTN4 |actininalpha4 family Bmember6 SERPINB6 |serpin LAMC3 |lamininsubunit gamma3 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta RAB5C |RAB5C, memberRASoncogenefamily FN1 |fibronectin1 COL27A1 |collagentypeXXVIIalpha1chain subunitITGB2 |integrin beta2 LAMB1 |lamininsubunit beta1 VCL |vinculin PRKCB |proteinkinaseCbeta ACTN1 |actininalpha1 LAMC1 |lamininsubunit gamma1 CXCL1 |C−X−Cmotifchemokineligand1 COL3A1 |collagentypeIIIalpha1chain LAMB3 |lamininsubunit beta3 COL1A1 |collagentypeIalpha1chain TGFB1 |transforming growth factor beta1 COL1A2 |collagentypeIalpha2chain LAMA4 |lamininsubunit alpha4 LAMC2 |lamininsubunit gamma2 COL4A1 |collagentypeIValpha1chain LAMA3 |lamininsubunit alpha3 COL4A2 |collagentypeIValpha2chain Amoebiasis hsa05146 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 20 and Histogram Color Key 101 0 −1 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Infectious disease CALML3 |calmodulinlike 3 SPHK1 |sphingosinekinase1 domaincontaining2 NOD2 |nucleotide bindingoligomerization bindingprotein LBP |lipopolysaccharide IFNB1 |interferon beta1 MAPK13 |mitogen−activated proteinkinase13 IFNA21 |interferon alpha21 subunit B,PPP3R2 |proteinphosphatase3regulatory beta IFNA5 |interferon alpha5 TLR9 |tolllike receptor9 1receptorassociatedkinase4 IRAK4 |interleukin 1alpha IL1A |interleukin MYD88 |myeloid response88 differentiation primary RAB5A |RAB5A,memberRASoncogenefamily 12B IL12B |interleukin FCGR2B |Fcfragment ofIgGreceptorIIb ATP6V1H |ATPase V1subunit H H+transporting 12A IL12A |interleukin BID |BH3interacting domaindeathagonist TIRAP |TIRdomaincontainingadaptorprotein MAPK12 |mitogen−activated proteinkinase12 CAMP |cathelicidinantimicrobialpeptide NFYC |nuclear factor transcription Ysubunit gamma ATP6V0C |ATPase V0subunit c H+transporting CREBBP |CREBbindingprotein LAMP1 |lysosomalassociatedmembrane protein1 ATP6AP1 |ATPase protein1 accessory H+transporting TNF |tumornecrosisfactor factor containingprotein RFXANK |regulatory Xassociatedankyrin TLR6 |tolllike receptor6 LAMP2 |lysosomalassociatedmembrane protein2 MAPK14 |mitogen−activated proteinkinase14 SPHK2 |sphingosinekinase2 subunit B,PPP3R1 |proteinphosphatase3regulatory alpha CTSD |cathepsinD ATP6V0D1 |ATPase V0subunit d1 H+transporting ARHGEF12 |Rhoguaninenucleotide exchange factor 12 FCGR1A |Fcfragment ofIgGreceptorIa BAD |BCL2associatedagonistofcelldeath FADD |Fas associatedviadeathdomain MAPK1 |mitogen−activated proteinkinase1 TLR2 |tolllike receptor2 CEBPG |CCAAT/enhancer binding proteingamma ATP6V0B |ATPase V0subunit b H+transporting ATP6V0A1 |ATPase V0subunit a1 H+transporting FCGR3B |Fcfragment ofIgGreceptorIIIb TLR1 |tolllike receptor1 subunitITGAX |integrin alphaX RHOA |ras homologfamily memberA oxideNOS2 |nitric synthase2 EP300 |E1Abindingproteinp300 RELA |proto−oncogene, NF−kBsubunit VDR |vitaminDreceptor JAK2 |Janus kinase2 BCL10 |B−cellCLL/lymphoma10 CASP8 |caspase8 CLEC4E |C−typelectindomainfamily 4memberE 1receptorassociatedkinase2 IRAK2 |interleukin PPP3CA |proteinphosphatase3catalyticsubunit alpha SRC |proto−oncogene, non−receptortyrosinekinase APAF1 |apoptoticpeptidaseactivating factor 1 KSR1 |kinasesuppressorofras 1 IFNGR2 |interferon gammareceptor2 CLEC7A |C−typelectindomaincontaining7A 1beta IL1B |interleukin TGFB3 |transforming growth factor beta3 RAB7A |RAB7A,memberRASoncogenefamily 10receptorsubunitIL10RB |interleukin beta TCIRG1 |T−cellimmune regulator1,ATPase V0subunit a3 H+transporting JAK1 |Janus kinase1 TNFRSF1A |TNFreceptorsuperfamily member1A SYK |spleenassociatedtyrosinekinase MAPK11 |mitogen−activated proteinkinase11 BAX |BCL2associatedX,apoptosisregulator NFKB1 |nuclear factor kappaBsubunit 1 CAMK2G |calcium/calmodulindependentproteinkinaseIIgamma subunitITGAM |integrin alphaM 18 IL18 |interleukin TGFB2 |transforming growth factor beta2 CD14 |molecule CASP10 |caspase10 BCL2 |BCL2,apoptosisregulator RAB5C |RAB5C, memberRASoncogenefamily CORO1A |coronin 1A FCER1G |Fcfragment ofIgEreceptorIg STAT1 |signaltransducer andactivator 1 oftranscription LSP1 |lymphocyte−specificprotein1 subunitITGB2 |integrin beta2 PLK3 |pololike kinase3 C3 |complement MAPK3 |mitogen−activated proteinkinase3 CEBPB |CCAAT/enhancer bindingproteinbeta MRC1 |mannosereceptorC−type1 IFNGR1 |interferon gammareceptor1 TGFB1 |transforming growth factor beta1 Tuberculosis hsa05152 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 15 and Histogram 1501 0 −1.5 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Infectious disease CLDN9 |claudin9 subunit Bgamma PPP2R2C |proteinphosphatase2regulatory CLDN14 |claudin14 subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory translation initiationfactorEIF2AK1 |eukaryotic 2alphakinase1 CLDN1 |claudin1 BRAF |B−Rafproto−oncogene, kinase serine/threonine IFNB1 |interferon beta1 MAPK13 |mitogen−activated proteinkinase13 IFNA21 |interferon alpha21 IFNA5 |interferon alpha5 IKBKE |inhibitorofnuclear factor kappaBkinasesubunit epsilon KRAS |proto−oncogene, GTPase CLDN6 |claudin6 subunit Balpha PPP2R2A |proteinphosphatase2regulatory CLDN2 |claudin2 growth factorEGF |epidermal TBK1 |TANK bindingkinase 1 MAPK12 |mitogen−activated proteinkinase12 CLDN19 |claudin19 PPARA |peroxisome proliferator activated receptoralpha PDPK1 |3−phosphoinositidedependentproteinkinase1 CLDN18 |claudin18 GSK3B |glycogensynthasekinase3beta MAVS antiviral signalingprotein |mitochondrial TNF |tumornecrosisfactor MAPK14 |mitogen−activated proteinkinase14 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha PIAS1 |proteininhibitorofactivated STAT 1 BAD |BCL2associatedagonistofcelldeath SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 IFNAR1 |interferon alphaandbeta receptorsubunit 1 PPP2CA |proteinphosphatase2catalyticsubunit alpha L RNASEL |ribonuclease STAT3 |signaltransducer andactivator 3 oftranscription MAPK1 |mitogen−activated proteinkinase1 IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma OAS1 |2'−5'−oligoadenylate synthetase1 PSME3 |proteasomeactivator subunit 3 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma ARAF |A−Rafproto−oncogene, kinase serine/threonine TYK2 |tyrosinekinase2 growth factorEGFR |epidermal receptor factorIRF3 |interferon 3 regulatory helix−loop−helixubiquitouskinase CHUK |conserved translation initiationfactorEIF2AK2 |eukaryotic 2alphakinase RELA |proto−oncogene, NF−kBsubunit SCARB1 |scavenger receptorclassBmember1 CLDN3 |claudin3 TICAM1 |tolllike receptoradaptormolecule1 IFNAR2 |interferon alphaandbetareceptorsubunit 2 NR1H3 |nuclear receptorsubfamily 1groupHmember3 PPP2CB |proteinphosphatase2catalyticsubunit beta subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta CLDN23 |claudin23 kinase1 RIPK1 |receptorinteracting serine/threonine JAK1 |Janus kinase1 TNFRSF1A |TNFreceptorsuperfamily member1A NRAS |proto−oncogene, GTPase MAPK11 |mitogen−activated proteinkinase11 factorIRF7 |interferon 7 regulatory TLR3 |tolllike receptor3 NFKB1 |nuclear factor kappaBsubunit 1 CLDN15 |claudin15 GRB2 |growth factor receptorboundprotein2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta STAT1 |signaltransducer andactivator 1 oftranscription OAS3 |2'−5'−oligoadenylate synthetase3 factorIRF1 |interferon 1 regulatory MAPK3 |mitogen−activated proteinkinase3 NFKBIA |NFKBinhibitoralpha CLDN4 |claudin4 CLDN7 |claudin7 CLDN5 |claudin5 Hepatitis C hsa05160 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 20 and Histogram 302 0 −3 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Infectious disease PIK3R2 | phosphoinositide−3−kinase regulatory subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory IFNB1 |interferon beta1 IFNA21 |interferon alpha21 IFNA5 |interferon alpha5 IKBKE |inhibitorofnuclear factor kappaBkinasesubunit epsilon MYD88 |myeloid response88 differentiation primary KRAS |proto−oncogene, GTPase CCNE2 |cyclinE2 PRKCG |proteinkinaseCgamma CCNA1 |cyclinA1 TIRAP |TIRdomaincontainingadaptorprotein TBK1 |TANK bindingkinase 1 MAP2K2 |mitogen−activated proteinkinase2 LAMTOR5 |lateendosomal/lysosomaladaptor, MAPKandMTOR activator 5 MAP2K1 |mitogen−activated proteinkinase1 factorE2F3 |E2Ftranscription 3 CREBBP |CREBbindingprotein MAVS antiviral signalingprotein |mitochondrial factorE2F2 |E2Ftranscription 2 ATP6AP1 |ATPase protein1 accessory H+transporting TNF |tumornecrosisfactor SMAD4 |SMADfamily member 4 MAP3K1 |mitogen−activated proteinkinase1 CREB5 |cAMPresponsive elementbindingprotein5 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha CDK2 |cyclindependentkinase2 CCNE1 |cyclinE1 BAD |BCL2associatedagonistofcelldeath IFNAR1 |interferon alphaandbeta receptorsubunit 1 DDX3X |DEAD−box helicase3,X−linked STAT3 |signaltransducer andactivator 3 oftranscription FADD |Fas associatedviadeathdomain MAPK1 |mitogen−activated proteinkinase1 TLR2 |tolllike receptor2 IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma factorE2F1 |E2Ftranscription 1 PTEN |phosphataseandtensinhomolog PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma factorIRF3 |interferon 3 regulatory helix−loop−helixubiquitous kinase CHUK |conserved EP300 |E1Abindingproteinp300 RELA |proto−oncogene, NF−kBsubunit TGFBR1 |transforming growth factor betareceptor1 CREB3L2 |cAMPresponsive elementbindingprotein3like 2 CASP8 |caspase8 TICAM1 |tolllike receptoradaptormolecule1 SRC |proto−oncogene, non−receptortyrosinekinase APAF1 |apoptoticpeptidaseactivating factor 1 CREB3 |cAMPresponsive element bindingprotein3 YWHAZ |tyrosine3−monooxygenase/tryptophan 5−monooxygenase activation proteinzeta ATF6B |activating factor transcription 6beta TGFB3 |transforming growth factor beta3 BIRC5 |baculoviral IAPrepeatcontaining5 NFATC4 |nuclear factor ofactivated T−cells4 subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta FAS |Fas cellsurface deathreceptor PTK2B |proteintyrosinekinase2beta JAK1 |Janus kinase1 NRAS |proto−oncogene, GTPase factorIRF7 |interferon 7 regulatory TLR3 |tolllike receptor3 BAX |BCL2associatedX,apoptosisregulator STAT5B |signaltransducer andactivator 5B oftranscription NFKB1 |nuclear factor kappaBsubunit 1 STAT6 |signaltransducer andactivator 6 oftranscription corepressor1 RB1 |RBtranscriptional 5−monooxygenaseYWHAB |tyrosine3−monooxygenase/tryptophan activation proteinbeta TGFB2 |transforming growth factor beta2 GRB2 |growth factor receptorboundprotein2 CASP10 |caspase10 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta BCL2 |BCL2,apoptosisregulator CCNA2 |cyclinA2 STAT1 |signaltransducer andactivator 1 oftranscription STAT5A |signaltransducer andactivator 5A oftranscription MAPK3 |mitogen−activated proteinkinase3 PRKCB |proteinkinaseCbeta NFKBIA |NFKBinhibitoralpha metallopeptidase9 MMP9 |matrix growth response2 EGR2 |early TGFB1 |transforming growth factor beta1 Hepatitis B hsa05161 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 3 and Histogram Color Key 050.5 −0.5 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243
SLC andabsorption Vitamin digestion
SS available undera APOA4 |apolipoproteinA4 familySLC19A2 |solutecarrier 19 member2 MMACHC |methylmalonic (cobalamindeficiency)cb aciduria factor intrinsic GIF |gastric familySLC19A1 |solutecarrier 19 member1 CUBN |cubilin PLB1 |phospholipaseB1 familySLC52A3 |solutecarrier 52member3 familySLC46A1 |solutecarrier 46member1 SCARB1 |scavenger receptorclass Bmember1 TCN2 |transcobalamin 2 hsa04977 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 10 and Histogram 101 0 −1 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Morphine addiction GNG4 |Gproteinsubunit gamma4 GNG13 |Gproteinsubunit gamma13 GABBR2 |gamma−aminobutyric acidtypeBreceptorsubunit 2 GNB3 |Gproteinsubunit beta3 KCNJ9 |potassiumvoltage−gated channelsubfamily Jmember9 GABRG3 |gamma−aminobutyric acidtypeAreceptorgamma3subunit PRKACG |proteinkinasecAMP−activated catalyticsubunit gamma OPRM1 |opioidreceptormu 1 GABRG2 |gamma−aminobutyric acidtypeAreceptorgamma2subunit KCNJ6 |potassiumvoltage−gated channelsubfamily Jmember6 GABRB1 |gamma−aminobutyric acidtypeAreceptorbeta1subunit GABRR2 |gamma−aminobutyric acidtypeAreceptorrho2subunit PDE10A |phosphodiesterase 10A PRKCG |proteinkinaseCgamma ADORA1 |adenosineA1receptor GABRR1 |gamma−aminobutyric acidtypeAreceptorrho1subunit GABRQ |gamma−aminobutyric acidtypeAreceptorthetasubunit GABRA3 |gamma−aminobutyric acidtypeAreceptoralpha3subunit GNGT1 |Gproteinsubunit gammatransducin 1 PRKACB |proteinkinasecAMP−activated catalyticsubunit beta GNG7 |Gproteinsubunit gamma7 GABBR1 |gamma−aminobutyric acidtypeBreceptorsubunit 1 GNAI3 |Gproteinsubunit alphai3 GNAI1 |Gproteinsubunit alphai1 GNB2 |Gproteinsubunit beta2 GNG5 |Gproteinsubunit gamma5 GNG8 |Gproteinsubunit gamma8 PDE7B |phosphodiesterase 7B PDE3B |phosphodiesterase 3B GRK3 |Gprotein−coupledreceptorkinase3 GNB1 |Gproteinsubunit beta1 ADCY6 |adenylate cyclase6 GRK2 |Gprotein−coupledreceptorkinase2 ARRB2 |arrestinbeta2 GNB4 |Gproteinsubunit beta4 GABRD |gamma−aminobutyric acidtypeAreceptordeltasubunit GRK6 |Gprotein−coupledreceptorkinase6 ARRB1 |arrestinbeta1 GNG12 |Gproteinsubunit gamma12 PDE3A |phosphodiesterase 3A GNG2 |Gproteinsubunit gamma2 GNAI2 |Gproteinsubunit alphai2 ADCY3 |adenylate cyclase3 PRKCB |proteinkinaseCbeta ADCY4 |adenylate cyclase4 hsa05032 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243
SLC ineukaryotesRibosome biogenesis
SS available undera REXO2 |RNAexonuclease 2 GNL3L |Gproteinnucleolar 3like P/MRPsubunitPOP7 |homolog,ribonuclease CSNK2B |caseinkinase2beta CSNK2A1 |caseinkinase2alpha1 factorNXT2 |nuclear 2like transport factor export 2 translation initiationfactorEIF6 |eukaryotic 6 biogenesisfactorTCOF1 |treacleribosome 1 PandMRPsubunitRPP25 |ribonuclease p25 XRN2 |5'−3'exoribonuclease 2 NOP10 |ribonucleoprotein P/MRPsubunitPOP4 |homolog,ribonuclease HEATR1 |HEAT repeatcontaining1 XRN1 |5'−3'exoribonuclease 1 hsa03008 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 6 and Histogram Color Key 11 −1 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC
SS p53 signalingpathway available undera STEAP3 |metalloreductase 1 SESN1 |sestrin CCNB3 |cyclinB3 TSC2 |TSCcomplex subunit 2 3 SESN3 |sestrin SHISA5 |shisafamily member5 ZMAT3 3 |zincfingermatrin−type MDM4 |MDM4,p53regulator CCNE2 |cyclinE2 CCNG1 |cyclinG1 SFN |stratifin ADGRB1 |adhesionGprotein−coupledreceptorB1 BID |BH3interacting domaindeathagonist 2 SESN2 |sestrin fingerandCHYzincdomain containing1 RCHY1 |ring CHEK1 |checkpointkinase1 MDM2 |proto−oncogene CDK2 |cyclindependentkinase2 CCNE1 |cyclinE1 TP73 |tumorproteinp73 TP53I3 |tumorproteinp53inducible protein3 family Bmember5 SERPINB5 |serpin PTEN |phosphataseandtensinhomolog fingerandWDrepeatdomain2 RFWD2 |ring THBS1 |thrombospondin1 subunit M2 reductaseregulatory RRM2 |ribonucleotide CD82 |molecule CASP8 |caspase8 GTSE1 |G2andS−phaseexpressed 1 APAF1 |apoptoticpeptidaseactivating factor 1 CCNB1 |cyclinB1 PPM1D |proteinphosphatase, Mg2+/Mn2+dependent1D CDK1 |cyclindependentkinase1 CDKN2A |cyclindependentkinaseinhibitor2A FAS |Fas cellsurface deathreceptor BAX |BCL2associatedX,apoptosisregulator CCNB2 |cyclinB2 CCND3 |cyclinD3 CCND2 |cyclinD2 family Emember1 SERPINE1 |serpin hsa04115 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243
SLC Glycerophospholipid metabolism
SS available undera ETNK2 |ethanolaminekinase2 MBOAT2 |membrane boundO−acyltransferase domaincontaining2 LPIN2 |lipin2 PEMT |phosphatidylethanolamineN−methyltransferase LYPLA1 |lysophospholipase I PNPLA7 |patatinlike phospholipase domaincontaining7 PLA2G12A |phospholipaseA2groupXIIA LPIN1 |lipin1 CRLS1 |cardiolipinsynthase1 LPCAT3 |lysophosphatidylcholineacyltransferase 3 SELENOI |selenoproteinI AGPAT3 |1−acylglycerol−3−phosphateO−acyltransferase 3 GPAM |glycerol−3−phosphateacyltransferase, mitochondrial PLA2G2F |phospholipaseA2groupIIF MBOAT1 |membrane boundO−acyltransferase domaincontaining1 PCYT2 |phosphatecytidylyltransferase 2,ethanolamine PHOSPHO1 |phosphoethanolamine/phosphocholinephosphatase GPD1L |glycerol−3−phosphatedehydrogenase 1like PCYT1B |phosphatecytidylyltransferase 1,choline, beta DGKI |diacylglycerolkinaseiota LYPLA2 |lysophospholipase II ETNK1 |ethanolaminekinase1 MBOAT7 |membrane boundO−acyltransferase domaincontaining7 GPD2 |glycerol−3−phosphatedehydrogenase 2 DGKG |diacylglycerolkinasegamma GPAT4 |glycerol−3−phosphateacyltransferase 4 PLB1 |phospholipaseB1 CEPT1 |choline/ethanolaminephosphotransferase 1 synthase2 PTDSS2 |phosphatidylserine TAZ |tafazzin decarboxylasePISD |phosphatidylserine PLA2G15 |phospholipaseA2groupXV PLD1 |phospholipaseD1 PLD2 |phospholipaseD2 PLA2G12B |phospholipaseA2groupXIIB AGPAT1 |1−acylglycerol−3−phosphateO−acyltransferase 1 LPGAT1 |lysophosphatidylglycerolacyltransferase 1 DGKH |diacylglycerolkinaseeta CDS1 |CDP−diacylglycerolsynthase1 PCYT1A |phosphatecytidylyltransferase 1,choline, alpha GPCPD1 |glycerophosphocholinephosphodiesterase 1 PLA2G2D |phospholipaseA2groupIID CDS2 |CDP−diacylglycerolsynthase2 PGS1 |phosphatidylglycerophosphatesynthase1 PNPLA6 |patatinlike phospholipasedomaincontaining6 AGPAT4 |1−acylglycerol−3−phosphateO−acyltransferase 4 LPCAT2 |lysophosphatidylcholineacyltransferase 2 CHKA |cholinekinasealpha bloodACHE group) |acetylcholinesterase (Cartwright PLA2G4A |phospholipaseA2groupIVA hsa00564 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC Dorso−ventral axisformation SS available undera PIWIL1 |piwilike RNA−mediatedgenesilencing1 KRAS |proto−oncogene, GTPase PIWIL2 |piwilike RNA−mediatedgenesilencing2 MAP2K1 |mitogen−activated proteinkinase1 NOTCH2 |notch2 SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 MAPK1 |mitogen−activated proteinkinase1 SPIRE1 |spiretypeactinnucleation factor 1 ETV6 |ETSvariant 6 SPIRE2 |spiretypeactinnucleation factor 2 growth factorEGFR |epidermal receptor NOTCH3 |notch3 PIWIL4 |piwilike RNA−mediatedgenesilencing4 ETV7 |ETSvariant 7 NOTCH1 |notch1 GRB2 |growth factor receptorboundprotein2 MAPK3 |mitogen−activated proteinkinase3 factorETS2 |ETSproto−oncogene2,transcription NOTCH4 |notch4 hsa04320 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS Osteoclast differentiation available undera BLNK |B−celllinker TEC |tecproteintyrosinekinase subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory IFNB1 |interferon beta1 MAPK13 |mitogen−activated proteinkinase13 NOX3 |NADPHoxidase 3 subunit B,PPP3R2 |proteinphosphatase3regulatory beta 1alpha IL1A |interleukin FCGR2B |Fcfragment ofIgGreceptorIIb CALCR |calcitoninreceptor LILRA1 |leukocyte immunoglobulin like receptorA1 TNFSF11 |TNFsuperfamily member11 MAPK12 |mitogen−activated proteinkinase12 LILRA6 |leukocyte immunoglobulin like receptorA6 MAP2K1 |mitogen−activated proteinkinase1 proteinbeta1 SIRPB1 |signalregulatory NOX1 |NADPHoxidase 1 TNF |tumornecrosisfactor MAPK14 |mitogen−activated proteinkinase14 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha subunit B,PPP3R1 |proteinphosphatase3regulatory alpha FCGR1A |Fcfragment ofIgGreceptorIa LILRA5 |leukocyte immunoglobulin like receptorA5 OSCAR |osteoclastassociated,immunoglobulin−like receptor IFNAR1 |interferon alphaandbeta receptorsubunit 1 MAPK1 |mitogen−activated proteinkinase1 IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma LILRB2 |leukocyte immunoglobulin like receptorB2 LILRB1 |leukocyte immunoglobulin like receptorB1 FCGR3B |Fcfragment ofIgGreceptorIIIb PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma TYK2 |tyrosinekinase2 RAC1 |Racfamily smallGTPase 1 FOSL2 |FOSlike factor 2,AP−1transcription subunit helix−loop−helixubiquitous kinase CHUK |conserved RELA |proto−oncogene, NF−kBsubunit TGFBR1 |transforming growth factor betareceptor1 PPP3CA |proteinphosphatase3catalyticsubunit alpha SQSTM1 |sequestosome1 MAP2K6 |mitogen−activated proteinkinase6 IFNGR2 |interferon gammareceptor2 IFNAR2 |interferon alphaandbetareceptorsubunit 2 subunitITGB3 |integrin beta3 1beta IL1B |interleukin subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory FHL2 |four andahalfLIMdomains2 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta tyrosinekinase BTK |Bruton LILRB4 |leukocyte immunoglobulin like receptorB4 JAK1 |Janus kinase1 TNFRSF1A |TNFreceptorsuperfamily member1A SYK |spleenassociatedtyrosinekinase MAPK11 |mitogen−activated proteinkinase11 TYROBP |TYRO proteintyrosinekinasebinding NFKB1 |nuclear factor kappaBsubunit 1 LCP2 |lymphocytecytosolicprotein2 SOCS1 |suppressorofcytokinesignaling1 GAB2 |GRB2associatedbindingprotein2 SPI1 |Spi−1proto−oncogene PLCG2 |phospholipaseCgamma2 TGFB2 |transforming growth factor beta2 RELB |proto−oncogene, NF−kBsubunit GRB2 |growth factor receptorboundprotein2 NCF2 |neutrophilcytosolicfactor 2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta NCF4 |neutrophilcytosolicfactor 4 TNFRSF11A |TNFreceptorsuperfamily member11a FOSL1 |FOSlike factor 1,AP−1transcription subunit STAT1 |signaltransducer andactivator 1 oftranscription PPARG |peroxisome proliferator activated receptorgamma NFKB2 |nuclear factor kappaBsubunit 2 MAPK3 |mitogen−activated proteinkinase3 CYBB |cytochromeb−245betachain CSF1 |colony stimulating factor 1 receptorexpressed onmyeloidTREM2 |triggering cells2 CYBA |cytochromeb−245alphachain NFKBIA |NFKBinhibitoralpha CTSK |cathepsinK IFNGR1 |interferon gammareceptor1 TGFBR2 |transforming growth factor betareceptor2 TGFB1 |transforming growth factor beta1 SIRPA proteinalpha |signalregulatory hsa04380 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Focal adhesion RAC3 |Racfamily smallGTPase 3 COL2A1 |collagentypeIIalpha1chain DIAPH1 |diaphanousrelatedformin 1 subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory LAMA1 |lamininsubunit alpha1 MYLK2 |myosin lightchainkinase2 BRAF |B−Rafproto−oncogene, kinase serine/threonine MYL10 |myosin lightchain10 MYL7 |myosin lightchain7 ACTN3 |actininalpha3(gene/pseudogene) CAV3 |caveolin 3 RASGRF1 |Rasproteinspecificguaninenucleotide releasingfactor 1 MYL2 |myosin lightchain2 PRKCG |proteinkinaseCgamma ERBB2 |erb−b2receptortyrosinekinase2 ACTG1 |actingamma1 SHC4 |SHCadaptorprotein4 COL24A1 |collagentypeXXIValpha1chain PDGFC |plateletderived growth factor C subunitITGA2 |integrin alpha2 SHC2 |SHCadaptorprotein2 growth factorEGF |epidermal MYLK4 |myosin lightchainkinasefamily member4 subunitITGB8 |integrin beta8 MAP2K1 |mitogen−activated proteinkinase1 SHC3 |SHCadaptorprotein3 CAPN2 |calpain2 PDPK1 |3−phosphoinositidedependentproteinkinase1 GSK3B |glycogensynthasekinase3beta PAK3 |p21(RAC1) activated kinase3 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha BAD |BCL2associatedagonistofcelldeath SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 subunitITGA11 |integrin alpha11 subunitITGA10 |integrin alpha10 bindingsialoprotein IBSP |integrin MAPK1 |mitogen−activated proteinkinase1 THBS3 |thrombospondin3 PARVG gamma |parvin PTEN |phosphataseandtensinhomolog PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma PAK2 |p21(RAC1) activated kinase2 growth factorEGFR |epidermal receptor RAC1 |Racfamily smallGTPase 1 THBS1 |thrombospondin1 RHOA |ras homologfamily memberA PPP1CA |proteinphosphatase1catalyticsubunit alpha SRC |proto−oncogene, non−receptortyrosinekinase CDC42 |celldivisioncycle42 PARVB beta |parvin XIAP |X−linked inhibitorofapoptosis subunitITGB3 |integrin beta3 MET |proto−oncogene, receptortyrosinekinase CRK |proto−oncogene, adaptorprotein BCAR1 |BCAR1,Casfamily scaffolding protein subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory MYL12A |myosin lightchain12A VAV1 |vav guaninenucleotide exchange factor 1 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta subunit 12A PPP1R12A |proteinphosphatase1regulatory ROCK1 |Rhoassociatedcoiled−coilcontainingproteinkinase1 FLNB |filaminB subunitITGB5 |integrin beta5 TNC |tenascinC ACTB |actinbeta COL5A1 |collagentypeValpha1chain COL5A2 |collagentypeValpha2chain VEGFA |vascular endothelialgrowth factor A THBS2 |thrombospondin2 PAK1 |p21(RAC1) activated kinase1 SPP1 |secretedphosphoprotein1 subunit 12C PPP1R12C |proteinphosphatase1regulatory COL5A3 |collagentypeValpha3chain RAP1A |RAP1A,memberofRASoncogenefamily DOCK1 |dedicatorofcytokinesis1 ACTN4 |actininalpha4 MYL12B |myosin lightchain12B GRB2 |growth factor receptorboundprotein2 CTNNB1 |cateninbeta1 LAMC3 |lamininsubunit gamma3 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta BCL2 |BCL2,apoptosisregulator ROCK2 |Rhoassociated coiled−coilcontainingproteinkinase2 subunitITGA7 |integrin alpha7 subunitITGA1 |integrin alpha1 TLN2 |talin2 FN1 |fibronectin1 COL27A1 |collagentypeXXVIIalpha1chain linkedILK |integrin kinase CCND3 |cyclinD3 LAMB1 |lamininsubunit beta1 SHC1 |SHCadaptorprotein1 MAPK3 |mitogen−activated proteinkinase3 PXN |paxillin VCL |vinculin VASP |vasodilator stimulated phosphoprotein PRKCB |proteinkinaseCbeta domainreceptor KDR |kinaseinsert ACTN1 |actininalpha1 VEGFC |vascular endothelialgrowth factor C FLT1 |fmsrelated tyrosinekinase1 PDGFB |plateletderived growth factor subunit B PGF |placentalgrowth factor TLN1 |talin1 LAMC1 |lamininsubunit gamma1 COL3A1 |collagentypeIIIalpha1chain LAMB3 |lamininsubunit beta3 COL1A1 |collagentypeIalpha1chain COL6A3 |collagentypeVIalpha3chain TNXB |tenascinXB CCND2 |cyclinD2 VWF |von Willebrand factor COL1A2 |collagentypeIalpha2chain ZYX |zyxin LAMA4 |lamininsubunit alpha4 subunitITGA3 |integrin alpha3 LAMC2 |lamininsubunit gamma2 CAV2 |caveolin 2 COL4A1 |collagentypeIValpha1chain FLNA |filaminA subunitITGA5 |integrin alpha5 LAMA3 |lamininsubunit alpha3 RAC2 |Racfamily smallGTPase 2 MYL9 |myosin lightchain9 COL4A2 |collagentypeIValpha2chain hsa04510 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS available undera Adherens junction NECTIN4 |nectincelladhesionmolecule 4 RAC3 |Racfamily smallGTPase 3 BAIAP2 |BAI1associatedprotein2 ACTN3 |actininalpha3(gene/pseudogene) ERBB2 |erb−b2receptortyrosinekinase2 ACTG1 |actingamma1 WASF1 |WAS proteinfamily member1 WASL |Wiskott−Aldrich syndromelike LMO7 |LIMdomain7 CREBBP |CREBbindingprotein CSNK2B |caseinkinase2beta CTNNA1 |cateninalpha1 SMAD4 |SMADfamily member4 PARD3 |par−3family regulator cellpolarity CSNK2A1 |caseinkinase2alpha1 PTPRJ |proteintyrosinephosphatase, receptortypeJ FARP2 domainprotein2 |FERM,ARH/RhoGEFandpleckstrin MAPK1 |mitogen−activated proteinkinase1 growth factorEGFR |epidermal receptor RAC1 |Racfamily smallGTPase 1 RHOA |ras homologfamily memberA EP300 |E1Abindingproteinp300 TGFBR1 |transforming growth factor betareceptor1 INSR |insulinreceptor SRC |proto−oncogene, non−receptortyrosinekinase CDC42 |celldivisioncycle42 PTPRF |proteintyrosinephosphatase, receptortypeF MET |proto−oncogene, receptortyrosinekinase IQGAP1 |IQmotifcontainingGTPase activating protein1 NECTIN2 |nectincelladhesionmolecule2 WAS |Wiskott−Aldrich syndrome WASF2 |WAS proteinfamily member2 PTPN1 |proteintyrosinephosphatase, non−receptortype1 ACTB |actinbeta PTPN6 |proteintyrosinephosphatase, non−receptortype6 factorTCF7L2 |transcription 7like 2 ACTN4 |actininalpha4 CTNNB1 |cateninbeta1 SNAI2 |snailfamily repressor2 transcriptional MAPK3 |mitogen−activated proteinkinase3 VCL |vinculin ACTN1 |actininalpha1 SNAI1 |snailfamily repressor1 transcriptional factorTCF7L1 |transcription 7like 1 TGFBR2 |transforming growth factor betareceptor2 RAC2 |Racfamily smallGTPase 2 hsa04520 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC
SS Synaptic vesicle cycle available undera ATP6V0E2 |ATPase V0 subunit e2 H+transporting ATP6V1C2 |ATPase V1subunit C2 H+ transporting familySLC18A3 |solutecarrier 18memberA3 UNC13A |unc−13homologA ATP6V1F |ATPase V1subunit F H+transporting CLTCL1 heavy |clathrin chainlike 1 RIMS1 |regulatingsynapticmembrane exocytosis 1 NSF |N−ethylmaleimide sensitive factor, vesicle fusingATPase familySLC17A6 |solutecarrier 17member6 ATP6V1B1 |ATPase V1subunit B1 H+transporting STX1B |syntaxin1B familySLC18A1 |solutecarrier 18memberA1 ATP6V1H |ATPase V1subunit H H+transporting ATP6V1A |ATPase V1subunit A H+transporting CLTA lightchainA |clathrin STX3 |syntaxin3 DNM3 |dynamin3 ATP6V0C |ATPase V0subunit c H+transporting AP2S1 |adaptorrelatedproteincomplex 2sigma1subunit SNAP25 |synaptosomeassociatedprotein25 STX1A |syntaxin1A ATP6V0D1 |ATPase V0subunit d1 H+transporting NAPA |NSFattachmentproteinalpha ATP6V1B2 |ATPase V1subunit B2 H+transporting ATP6V0E1 |ATPase V0subunit e1 H+transporting AP2A1 |adaptorrelatedproteincomplex 2alpha1subunit CLTC heavy |clathrin chain CLTB lightchainB |clathrin DNM1 |dynamin1 ATP6V0B |ATPase V0subunit b H+transporting ATP6V0A1 |ATPase V0subunit a1 H+transporting AP2A2 |adaptorrelatedproteincomplex 2alphasubunit SYT1 |synaptotagmin1 DNM2 |dynamin2 AP2M1 |adaptorrelatedproteincomplex 2mu 1subunit CPLX1 |complexin 1 ATP6V1E1 |ATPase V1subunit E1 H+transporting ATP6V1C1 |ATPase V1subunit C1 H+transporting TCIRG1 |T−cellimmune regulator1,ATPase V0subunit a3 H+transporting AP2B1 |adaptorrelatedproteincomplex 2beta1subunit VAMP2 |vesicle associatedmembrane protein2 hsa04721 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC Regulation ofactincytoskeleton
SS available undera SCIN |scinderin RAC3 |Racfamily smallGTPase 3 CYFIP2 |cytoplasmicFMR1interacting protein2 BAIAP2 |BAI1associatedprotein2 IQGAP3 |IQmotifcontainingGTPase activating protein3 FGD1 |FYVE,RhoGEFandPHdomaincontaining1 DIAPH1 |diaphanousrelatedformin 1 subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory PFN4 |profilinfamily member4 TIAM1 |T−celllymphomainvasion andmetastasis1 MYLK2 |myosin lightchainkinase2 SSH3 |slingshotproteinphosphatase3 FGF5 |fibroblast growth factor 5 BRAF |B−Rafproto−oncogene, kinase serine/threonine TMSB4Y |thymosin beta4,Y−linked FGF4 |fibroblast growth factor 4 FGF6 |fibroblast growth factor 6 5 CHRM5 |cholinergicreceptormuscarinic MYL10 |myosin lightchain10 FGF17 |fibroblast growth factor 17 MYL7 |myosin lightchain7 ACTN3 |actininalpha3(gene/pseudogene) FGF20 |fibroblast growth factor 20 FGF22 |fibroblast growth factor 22 4 CHRM4 |cholinergicreceptormuscarinic FGF14 |fibroblast growth factor 14 MYL2 |myosin lightchain2 KRAS |proto−oncogene, GTPase FGF19 |fibroblast growth factor 19 FGF11 |fibroblast growth factor 11 ACTG1 |actingamma1 PDGFC |plateletderived growth factor C WASF1 |WAS proteinfamily member1 subunitITGA2 |integrin alpha2 DIAPH3 |diaphanousrelatedformin 3 DIAPH2 |diaphanousrelatedformin 2 BDKRB1 |bradykinin receptorB1 WASL |Wiskott−Aldrich syndromelike growth factorEGF |epidermal MYLK4 |myosin lightchainkinasefamily member4 FGF12 |fibroblast growth factor 12 subunitITGB8 |integrin beta8 BRK1 |BRICK1,SCAR/WAVE actinnucleating complex subunit MAP2K2 |mitogen−activated proteinkinase2 NCKAP1 |NCKassociatedprotein1 MAP2K1 |mitogen−activated proteinkinase1 FGF9 |fibroblast growth factor 9 FGF1 |fibroblast growth factor 1 PAK3 |p21(RAC1) activated kinase3 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha ARHGEF12 |Rhoguaninenucleotide exchange factor 12 PIP5K1A |phosphatidylinositol−4−phosphate5−kinasetype1alpha SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 LIMK1 |LIMdomainkinase1 subunitITGA11 |integrin alpha11 PIP4K2A |phosphatidylinositol−5−phosphate4−kinasetype2alpha ARPC2 |actinrelatedprotein2/3complex subunit 2 subunitITGA10 |integrin alpha10 FGFR3 |fibroblast growth factor receptor3 CYFIP1 |cytoplasmicFMR1interacting protein 1 MAPK1 |mitogen−activated proteinkinase1 FGD3 |FYVE,RhoGEFandPHdomaincontaining3 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma ARAF |A−Rafproto−oncogene, kinase serine/threonine PAK2 |p21(RAC1) activated kinase2 subunitITGAX |integrin alphaX growth factorEGFR |epidermal receptor RAC1 |Racfamily smallGTPase 1 APC |APC, WNTsignalingpathway regulator RHOA |ras homologfamily memberA ENAH |ENAH,actinregulator PPP1CA |proteinphosphatase1catalyticsubunit alpha SSH2 |slingshotproteinphosphatase2 ARHGEF7 |Rhoguaninenucleotide exchange factor 7 ARPC3 |actinrelatedprotein2/3complex subunit 3 PIP4K2C |phosphatidylinositol−5−phosphate4−kinasetype2gamma SRC |proto−oncogene, non−receptortyrosinekinase CDC42 |celldivisioncycle42 familySLC9A1 |solutecarrier 9memberA1 ARHGEF4 |Rhoguaninenucleotide exchange factor 4 subunitITGB3 |integrin beta3 SSH1 |slingshotproteinphosphatase1 CRK |proto−oncogene, adaptorprotein BCAR1 |BCAR1,Casfamily scaffolding protein subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory IQGAP1 |IQmotifcontainingGTPase activating protein1 MYL12A |myosin lightchain12A VAV1 |vav guaninenucleotide exchange factor 1 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta subunit 12A PPP1R12A |proteinphosphatase1regulatory WAS |Wiskott−Aldrich syndrome WASF2 |WAS proteinfamily member2 NRAS |proto−oncogene, GTPase ROCK1 |Rhoassociated coiled−coilcontainingproteinkinase1 LIMK2 |LIMdomainkinase2 ARPC4 |actinrelatedprotein2/3complex subunit 4 subunitITGB5 |integrin beta5 NCKAP1L |NCKassociatedprotein1like F2R |coagulationfactor IIthrombinreceptor CFL1 |cofilin1 ACTB |actinbeta PFN1 |profilin1 ARPC1A |actinrelatedprotein2/3complex subunit 1A PAK1 |p21(RAC1) activated kinase1 GNG12 |Gproteinsubunit gamma12 subunitITGAM |integrin alphaM subunit 12C PPP1R12C |proteinphosphatase1regulatory CD14 |molecule DOCK1 |dedicatorofcytokinesis1 ACTN4 |actininalpha4 MYL12B |myosin lightchain12B CFL2 |cofilin2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta ROCK2 |Rhoassociated coiled−coilcontainingproteinkinase2 MYH9 |myosin heavy chain9 subunitITGA7 |integrin alpha7 subunitITGA1 |integrin alpha1 GNA13 |Gproteinsubunit alpha13 FN1 |fibronectin1 subunitITGB2 |integrin beta2 PIP5K1B |phosphatidylinositol−4−phosphate5−kinasetype1beta MAPK3 |mitogen−activated proteinkinase3 ARPC5 |actinrelatedprotein2/3complex subunit 5 PXN |paxillin VCL |vinculin ACTN1 |actininalpha1 MYH14 |myosin heavy chain14 PDGFB |plateletderived growth factor subunit B ARPC1B |actinrelatedprotein2/3complex subunit 1B GSN |gelsolin FGFR4 |fibrobla hsa04810 ; this versionpostedFebruary19,2020. 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CA doi: https://doi.org/10.1101/635243
SLC Amyotrophic lateralsclerosis (ALS)
SS available undera SOD1 |superoxide dismutase 1 GRIN2C |glutamateionotropicreceptorNMDA typesubunit 2C MAPK13 |mitogen−activated proteinkinase13 MAP3K5 |mitogen−activated proteinkinase5 subunit B,PPP3R2 |proteinphosphatase3regulatory beta TOMM40L membrane |translocase 40like ofoutermitochondrial RAB5A |RAB5A,memberRASoncogenefamily GRIA1 |glutamateionotropicreceptorAMPA typesubunit 1 BID |BH3interacting domaindeath agonist MAPK12 |mitogen−activated proteinkinase12 GRIN2A |glutamateionotropicreceptorNMDA typesubunit 2A TNF |tumornecrosisfactor MAPK14 |mitogen−activated proteinkinase14 subunit B,PPP3R1 |proteinphosphatase3regulatory alpha BAD |BCL2associatedagonistofcelldeath DAXX |deathdomainassociatedprotein 1 DERL1 |derlin BCL2L1 |BCL2like 1 RAC1 |Racfamily smallGTPase 1 GRIN2D |glutamateionotropicreceptorNMDA typesubunit 2D PPP3CA |proteinphosphatase3catalyticsubunit alpha APAF1 |apoptotic peptidaseactivating factor 1 MAP2K6 |mitogen−activated proteinkinase6 TNFRSF1A |TNFreceptorsuperfamily member 1A MAPK11 |mitogen−activated proteinkinase11 BAX |BCL2associatedX,apoptosisregulator BCL2 |BCL2,apoptosisregulator CASP1 |caspase1 TNFRSF1B |TNFreceptorsuperfamily member 1B hsa05014 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 25 and Histogram 1501 0 −1.5 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC
SS available undera CALML3 |calmodulinlike 3 HIST3H2A |histonecluster3H2A GNG4 |Gproteinsubunit gamma4 H2AFY2 |H2Ahistonefamily memberY2 TH |tyrosinehydroxylase HIST1H2AM |histonecluster1H2Afamily memberm HIST1H2BL |histonecluster1H2Bfamily memberl HIST1H2AJ |histonecluster1H2Afamily memberj GNG13 |Gproteinsubunit gamma13 DRD2 |dopaminereceptorD2 GNB3 |Gproteinsubunit beta3 HIST1H3E |histonecluster1H3family membere HIST1H2AB |histonecluster1H2Afamily memberb DDC |dopadecarboxylase HIST3H3 |histonecluster3H3 GRIN2C |glutamateionotropicreceptorNMDA typesubunit 2C HIST1H2BB |histonecluster1H2Bfamily memberb BRAF |B−Rafproto−oncogene, kinase serine/threonine HIST2H2AA3 |histonecluster2H2Afamily membera3 H2AFJ |H2Ahistonefamily memberJ familySLC18A1 |solutecarrier 18memberA1 PKIA |cAMP−dependentproteinkinaseinhibitoralpha HIST1H2BM |histonecluster1H2Bfamily memberm KRAS |proto−oncogene, GTPase ADORA2A |adenosineA2areceptor HIST1H2BO |histonecluster1H2Bfamily membero HIST1H2BN |histonecluster1H2Bfamily membern familySLC6A3 |solutecarrier 6member3 GRIN3B |glutamateionotropicreceptorNMDA typesubunit 3B SHC4 |SHCadaptorprotein4 GRIN3A |glutamateionotropicreceptorNMDA typesubunit 3A HDAC8 |histonedeacetylase8 SHC2 |SHCadaptorprotein2 HIST1H2BC |histonecluster1H2Bfamily memberc HIST1H3H |histonecluster1H3family memberh GNGT1 |Gproteinsubunit gammatransducin 1 MAP2K1 |mitogen−activated proteinkinase1 GRIN2A |glutamateionotropicreceptorNMDA typesubunit 2A H2AFY |H2Ahistonefamily memberY H3F3A |H3histonefamily member3A GNG7 |Gproteinsubunit gamma7 SHC3 |SHCadaptorprotein3 H2AFZ |H2Ahistonefamily memberZ GNAI3 |Gproteinsubunit alphai3 HDAC11 |histonedeacetylase11 GNAI1 |Gproteinsubunit alphai1 CREB5 |cAMPresponsive element bindingprotein5 GNB2 |Gproteinsubunit beta2 SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 CAMKK1 |calcium/calmodulindependentproteinkinase1 GNG5 |Gproteinsubunit gamma5 GNG8 |Gproteinsubunit gamma8 MAPK1 |mitogen−activated proteinkinase1 HIST2H2BE |histonecluster2H2Bfamily membere HIST1H2BH |histonecluster1H2Bfamily memberh HIST1H2BD |histonecluster1H2Bfamily memberd HDAC5 |histonedeacetylase5 H2AFV |H2Ahistonefamily memberV ARAF |A−Rafproto−oncogene, kinase serine/threonine HIST1H2BJ |histonecluster1H2Bfamily memberj GRIN2D |glutamateionotropicreceptorNMDA typesubunit 2D CREB3L2 |cAMPresponsive elementbindingprotein3like 2 PPP1CA |proteinphosphatase1catalyticsubunit alpha GNB1 |Gproteinsubunit beta1 CREB3 |cAMPresponsive element bindingprotein3 ATF6B |activating factor transcription 6beta GNB4 |Gproteinsubunit beta4 H2AFX |H2Ahistonefamily memberX NRAS |proto−oncogene, GTPase CAMKK2 |calcium/calmodulindependentproteinkinase2 HIST1H2BK |histonecluster1H2Bfamily memberk ADORA2B |adenosineA2breceptor GNG12 |Gproteinsubunit gamma12 HDAC7 |histonedeacetylase7 GRB2 |growth factor receptorboundprotein2 GNG2 |Gproteinsubunit gamma2 GNAI2 |Gproteinsubunit alphai2 SHC1 |SHCadaptorprotein1 MAPK3 |mitogen−activated proteinkinase3 inhibitorsubunit 1B PPP1R1B |proteinphosphatase1regulatory Alcoholism hsa05034 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 4 and Histogram 1501 0 −1.5 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC
SS immunodeficiencyPrimary available undera BLNK |B−celllinker RAG2 |recombinationactivating 2 AICDA |activation inducedcytidinedeaminase TNFRSF13B |TNFreceptorsuperfamily member13B DCLRE1C |DNAcross−linkrepair1C factor containing protein Xassociatedankyrin RFXANK |regulatory IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma tyrosinekinase BTK |Bruton JAK3 |Janus kinase3 TAP2 2,ATP |transporter bindingcassettesubfamily Bmember PTPRC |proteintyrosinephosphatase, receptortypeC TAP1 1,ATP |transporter bindingcassettesubfamily Bmember 2receptorsubunitIL2RG |interleukin gamma hsa05340 ; this versionpostedFebruary19,2020. Other CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 60 and Histogram 302 0 −3 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC MAPK signalingpathway
Signal transduction SS available undera MAPKAPK3 |mitogen−activated proteinkinase−activated proteinkinase3 RAC3 |Racfamily smallGTPase 3 DUSP5 |dualspecificityphosphatase 5 HSPA6 |heatshockproteinfamily A(Hsp70)member6 CACNA2D2 subunit |calciumvoltage−gated alpha2delta2 channelauxiliary CACNA2D3 subunit |calciumvoltage−gated alpha2delta3 channelauxiliary CACNB3 subunit |calciumvoltage−gated beta3 channelauxiliary FGF5 |fibroblast growth factor 5 CACNG7 subunit |calciumvoltage−gated gamma7 channelauxiliary BRAF |B−Rafproto−oncogene, kinase serine/threonine FGF4 |fibroblast growth factor 4 CACNB4 subunit |calciumvoltage−gated beta4 channelauxiliary PRKACG |proteinkinasecAMP−activated catalyticsubunit gamma NTF3 |neurotrophin3 MAPK13 |mitogen−activated proteinkinase13 MAP3K5 |mitogen−activated proteinkinase5 FGF6 |fibroblast growth factor 6 subunit B,PPP3R2 |proteinphosphatase3regulatory beta CACNG2 subunit |calciumvoltage−gated gamma2 channelauxiliary CACNA1E |calciumvoltage−gated channelsubunit alpha1E CACNG1 subunit |calciumvoltage−gated gamma1 channelauxiliary NTF4 |neurotrophin4 FGF17 |fibroblast growth factor 17 FGF20 |fibroblast growth factor 20 1alpha IL1A |interleukin FGF22 |fibroblast growth factor 22 CACNG8 subunit |calciumvoltage−gated gamma8 channelauxiliary CACNG5 subunit |calciumvoltage−gated gamma5 channelauxiliary FGF14 |fibroblast growth factor 14 RASGRF1 |Rasproteinspecificguaninenucleotide releasingfactor 1 KRAS |proto−oncogene, GTPase FGF19 |fibroblast growth factor 19 CACNG6 subunit |calciumvoltage−gated gamma6 channelauxiliary PRKCG |proteinkinaseCgamma FGF11 |fibroblast growth factor 11 CACNA1F |calciumvoltage−gated channelsubunit alpha1F CACNA1D |calciumvoltage−gated channelsubunit alpha1D proteinS6kinaseA5 RPS6KA5 |ribosomal MAX |MYCassociatedfactor X growth factorEGF |epidermal MAP2K5 |mitogen−activated proteinkinase5 FGF12 |fibroblast growth factor 12 MAPK12 |mitogen−activated proteinkinase12 MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 FGF9 |fibroblast growth factor 9 PRKACB |proteinkinasecAMP−activated catalyticsubunit beta FGF1 |fibroblast growth factor 1 HSPA1L |heatshockproteinfamily A(Hsp70)member1like TNF |tumornecrosisfactor proteinS6kinaseA3 RPS6KA3 |ribosomal MAPK14 |mitogen−activated proteinkinase14 PPP5C |proteinphosphatase5catalyticsubunit MAP3K1 |mitogen−activated proteinkinase1 RASA2 |RASp21proteinactivator 2 subunit B,PPP3R1 |proteinphosphatase3regulatory alpha RASGRP4 |RASguanyl releasingprotein4 DDIT3 |DNAdamageinducible 3 transcript 1receptortype2 IL1R2 |interleukin SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 kinase3 STK3 |serine/threonine MAPKAPK2 |mitogen−activated proteinkinase−activated proteinkinase2 DUSP6 |dualspecificityphosphatase6 FGFR3 |fibroblast growth factor receptor3 MAPK1 |mitogen−activated proteinkinase1 CACNB1 subunit |calciumvoltage−gated beta1 channelauxiliary TAOK1 |TAO kinase1 RAPGEF2 |Rapguaninenucleotide exchange factor 2 IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma DAXX |deathdomainassociatedprotein PAK2 |p21(RAC1) activated kinase2 growth factorEGFR |epidermal receptor NF1 |neurofibromin1 MAPK7 |mitogen−activated proteinkinase7 RAC1 |Racfamily smallGTPase 1 MAP3K2 |mitogen−activated proteinkinase2 helix−loop−helixubiquitouskinase CHUK |conserved RELA |proto−oncogene, NF−kBsubunit MAP3K6 |mitogen−activated proteinkinase6 TGFBR1 |transforming growth factor betareceptor1 HSPB1 |heatshockproteinfamily B(small)member1 MAP3K13 |mitogen−activated proteinkinase13 PPP3CA |proteinphosphatase3catalyticsubunit alpha CDC42 |celldivisioncycle42 kinase1 MKNK1 |MAPkinaseinteracting serine/threonine MAP2K6 |mitogen−activated proteinkinase6 MAP4K4 |mitogen−activated proteinkinase4 TAOK2 |TAO kinase2 1beta IL1B |interleukin TGFB3 |transforming growth factor beta3 ARRB2 |arrestinbeta2 CRK |proto−oncogene, adaptorprotein TAOK3 |TAO kinase3 kinase4 STK4 |serine/threonine MAP3K3 |mitogen−activated proteinkinase3 FAS |Fas cellsurface deathreceptor TNFRSF1A |TNFreceptorsuperfamily member1A NRAS |proto−oncogene, GTPase FLNB |filaminB MAPK11 |mitogen−activated proteinkinase11 PTPN7 |proteintyrosinephosphatase, non−receptortype7 ARRB1 |arrestinbeta1 NFKB1 |nuclear factor kappaBsubunit 1 PAK1 |p21(RAC1) activated kinase1 MAP3K11 |mitogen−activated proteinkinase11 proteinS6kinaseA1 RPS6KA1 |ribosomal GNG12 |Gproteinsubunit gamma12 RASGRP2 |RASguanyl releasingprotein2 RAP1A |RAP1A,memberofRASoncogenefamily TGFB2 |transforming growth factor beta2 CD14 |molecule RELB |proto−oncogene, NF−kBsubunit GRB2 |growth factor receptorboundprotein2 MAP3K20 |mitogen−activated proteinkinase20 PLA2G4A |phospholipaseA2groupIVA response factorSRF |serum NFKB2 |nuclear factor kappaBsubunit 2 MAPK3 |mitogen−activated proteinkinase3 MAP3K8 |mitogen−activated proteinkinase8 PRKCB |proteinkinaseCbeta PDGFB |plateletderived growth hsa04010 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 6 and Histogram 101 0 −1 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC ErbB signalingpathway
Signal transduction SS available undera EIF4EBP1 | eukaryotic translation initiationfactorEIF4EBP1 |eukaryotic 4Ebindingprotein1 BTC |betacellulin subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory EREG |epiregulin kinase BRAF |B−Rafproto−oncogene, serine/threonine proteinS6kinaseB2 RPS6KB2 |ribosomal KRAS |proto−oncogene, GTPase PRKCG |proteinkinaseCgamma ERBB2 |erb−b2receptortyrosinekinase2 SHC4 |SHCadaptorprotein4 SHC2 |SHCadaptorprotein2 growth factorEGF |epidermal MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 NRG2 |neuregulin2 SHC3 |SHCadaptorprotein3 GSK3B |glycogensynthasekinase3beta PAK3 |p21(RAC1) activated kinase3 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha NRG1 |neuregulin1 ABL2 |ABLproto−oncogene2,non−receptortyrosinekinase BAD |BCL2associatedagonistofcelldeath SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 MAPK1 |mitogen−activated proteinkinase1 CBL |Cbl proto−oncogene PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma kinase ARAF |A−Rafproto−oncogene, serine/threonine PAK2 |p21(RAC1) activated kinase2 growth factorEGFR |epidermal receptor SRC |proto−oncogene, non−receptortyrosinekinase GAB1 |GRB2associatedbindingprotein1 CRK |proto−oncogene, adaptorprotein subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta NRAS |proto−oncogene, GTPase STAT5B |signaltransducer andactivator 5B oftranscription PAK1 |p21(RAC1) activated kinase1 CAMK2G |calcium/calmodulindependentproteinkinaseIIgamma PLCG2 |phospholipaseCgamma2 GRB2 |growth factor receptorboundprotein2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta TGFA |transforming growth factor alpha SHC1 |SHCadaptorprotein1 STAT5A |signaltransducer andactivator 5A oftranscription MAPK3 |mitogen−activated proteinkinase3 PRKCB |proteinkinaseCbeta AREG |amphiregulin hsa04012 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 30 and Histogram 1501 0 −1.5 Color Key V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC Rap1 signalingpathway
Signal transduction SS available undera CALML3 |calmodulinlike 3 RAC3 |Racfamily smallGTPase 3 SKAP1 |srckinaseassociatedphosphoprotein 1 subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory PFN4 |profilinfamily member4 TIAM1 |T−celllymphomainvasion andmetastasis1 DRD2 |dopaminereceptorD2 FGF5 |fibroblast growth factor 5 A2 EFNA2 |ephrin BRAF |B−Rafproto−oncogene, kinase serine/threonine FGF4 |fibroblast growth factor 4 MAPK13 |mitogen−activated proteinkinase13 LPAR3 |lysophosphatidicacidreceptor3 FGF6 |fibroblast growth factor 6 LPAR2 |lysophosphatidicacidreceptor2 FGF17 |fibroblast growth factor 17 FGF20 |fibroblast growth factor 20 FGF22 |fibroblast growth factor 22 FGF14 |fibroblast growth factor 14 LPAR4 |lysophosphatidicacidreceptor4 KRAS |proto−oncogene, GTPase FGF19 |fibroblast growth factor 19 ADORA2A |adenosineA2areceptor PRKCG |proteinkinaseCgamma FGF11 |fibroblast growth factor 11 ACTG1 |actingamma1 PLCB4 |phospholipaseCbeta4 PDGFC |plateletderived growth factor C RGS14 |regulatorofGproteinsignaling14 growth factorEGF |epidermal FGF12 |fibroblast growth factor 12 MAPK12 |mitogen−activated proteinkinase12 MAP2K2 |mitogen−activated proteinkinase2 growthNGFR |nerve factor receptor MAP2K1 |mitogen−activated proteinkinase1 FGF9 |fibroblast growth factor 9 GRIN2A |glutamateionotropicreceptorNMDA typesubunit 2A ANGPT4 |angiopoietin4 GNAI3 |Gproteinsubunit alphai3 FGF1 |fibroblast growth factor 1 MAPK14 |mitogen−activated proteinkinase14 PARD3 |par−3family regulator cellpolarity GNAI1 |Gproteinsubunit alphai1 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha KIT |proto−oncogenereceptortyrosinekinase PLCE1 |phospholipaseCepsilon1 FGFR3 |fibroblast growth factor receptor3 FARP2 domainprotein2 |FERM,ARH/RhoGEFandpleckstrin DOCK4 |dedicatorofcytokinesis4 RAP1GAP |RAP1GTPase activating protein MAPK1 |mitogen−activated proteinkinase1 RAPGEF2 |Rapguaninenucleotide exchange factor 2 PARD6A |par−6family regulatoralpha cellpolarity SIPA1L2 |signalinducedproliferation associated1like 2 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma growth factorEGFR |epidermal receptor RAC1 |Racfamily smallGTPase 1 THBS1 |thrombospondin1 RHOA |ras homologfamily memberA GNAQ |Gproteinsubunit alphaq INSR |insulinreceptor ADCY6 |adenylate cyclase6 SRC |proto−oncogene, non−receptortyrosinekinase CDC42 |celldivisioncycle42 FPR1 |formyl peptide receptor1 PLCB2 |phospholipaseCbeta2 MAP2K6 |mitogen−activated proteinkinase6 RASSF5 |Rasassociationdomainfamily member5 subunitITGB3 |integrin beta3 MET |proto−oncogene, receptortyrosinekinase CRK |proto−oncogene, adaptorprotein BCAR1 |BCAR1,Casfamily scaffolding protein subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta RAPGEF3 |Rapguaninenucleotide exchange factor 3 ANGPT2 |angiopoietin2 NRAS |proto−oncogene, GTPase MAPK11 |mitogen−activated proteinkinase11 F2R |coagulationfactor IIthrombinreceptor ACTB |actinbeta ADORA2B |adenosineA2breceptor receptor3 F2RL3 |F2Rlike thrombinortrypsin PFN1 |profilin1 VEGFA |vascular endothelialgrowth factor A SIPA1 |signal−inducedproliferation−associated 1 LCP2 |lymphocytecytosolicprotein2 RALB |RASlike proto−oncogene B RASGRP2 |RASguanyl releasingprotein2 subunitITGAM |integrin alphaM RAP1A |RAP1A,memberofRASoncogenefamily CTNNB1 |cateninbeta1 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta FYB1 |FYNbindingprotein1 TLN2 |talin2 RAPGEF5 |Rapguaninenucleotide exchange factor 5 ANGPT1 |angiopoietin1 KITLG |KITligand subunitITGB2 |integrin beta2 GNAI2 |Gproteinsubunit alphai2 MAPK3 |mitogen−activated proteinkinase3 ADCY3 |adenylate cyclase3 CSF1 |colony stimulating factor 1 VASP |vasodilator stimulated phosphoprotein PRKCB |proteinkinaseCbeta domainreceptor KDR |kinaseinsert VEGFC |vascular endothelialgrowth factor C FLT1 |fmsrelated tyrosinekinase1 PDGFB |plateletderived growth factor subunit B PGF |placentalgrowth factor TLN1 |talin1 APBB1IP |amyloid betaprecursorproteinbindingfamily Bmember1interacting protein FGFR4 |fibroblast growth factor receptor4 ADCY4 |adenylate cyclase4 repeat andPHdomain3 ARAP3 |ArfGAPwithRhoGAPdomain,ankyrin RRAS |RASrelated RAC2 |Racfamily smallGTPase 2 hsa04015 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 15 and Histogram Color Key 11 −1 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC HIF−1 signalingpathway
Signal transduction SS available undera ENO3 |enolase3 translation initiationfactorEIF4EBP1 |eukaryotic 4Ebindingprotein1 PDHB |pyruvate dehydrogenase E1betasubunit PDHA1 |pyruvate dehydrogenase E1alpha1subunit subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory ELOB |elonginB ELOC |elonginC NOX3 |NADPHoxidase 3 proteinS6kinaseB2 RPS6KB2 |ribosomal NPPA peptideA |natriuretic EPO |erythropoietin LDHA |lactatedehydrogenase A PRKCG |proteinkinaseCgamma ERBB2 |erb−b2receptortyrosinekinase2 growth factorEGF |epidermal VHL |von Hippel−Lindautumorsuppressor MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 ANGPT4 |angiopoietin4 NOX1 |NADPHoxidase 1 CREBBP |CREBbindingprotein PGK1 |phosphoglycerate kinase1 ALDOA |aldolase, A fructose−bisphosphate PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha RBX1 |ring−box 1 ENO1 |enolase1 HK3 |hexokinase 3 EGLN1 |egl−9family hypoxia inducible factor 1 GAPDH |glyceraldehyde−3−phosphate dehydrogenase STAT3 |signaltransducer andactivator 3 oftranscription MAPK1 |mitogen−activated proteinkinase1 LTBR |lymphotoxin betareceptor PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma hydrocarbonARNT |aryl receptornuclear translocator growth factorEGFR |epidermal receptor translationEIF4E2 |eukaryotic initiationfactor 4Efamily member2 oxideNOS2 |nitric synthase2 EP300 |E1Abindingproteinp300 RELA |proto−oncogene, NF−kBsubunit INSR |insulinreceptor kinase1 MKNK1 |MAPkinaseinteracting serine/threonine IFNGR2 |interferon gammareceptor2 EGLN3 |egl−9family hypoxia inducible factor 3 EGLN2 |egl−9family hypoxia inducible factor 2 subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory HK2 |hexokinase 2 familySLC2A1 |solutecarrier 2member1 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta ANGPT2 |angiopoietin2 NFKB1 |nuclear factor kappaBsubunit 1 VEGFA |vascular endothelialgrowth factor A CAMK2G |calcium/calmodulindependentproteinkinaseIIgamma HIF1A |hypoxia inducible factor 1alphasubunit PLCG2 |phospholipaseCgamma2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta BCL2 |BCL2,apoptosisregulator 3 PFKFB3 |6−phosphofructo−2−kinase/fructose−2,6−biphosphatase TFRC |transferrin receptor ANGPT1 |angiopoietin1 MAPK3 |mitogen−activated proteinkinase3 CYBB |cytochromeb−245betachain TIMP1 |TIMPmetallopeptidaseinhibitor1 PRKCB |proteinkinaseCbeta FLT1 |fmsrelated tyrosinekinase1 HKDC1 |hexokinase domaincontaining1 IFNGR1 |interferon gammareceptor1 6receptor IL6R |interleukin EDN1 |endothelin1 family Emember1 SERPINE1 |serpin hsa04066 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 15 and Histogram Color Key 11 −1 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC FoxO signalingpathway
Signal transduction SS available undera BNIP3 |BCL2interacting protein3 subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory kinase2 SGK2 |SGK2,serine/threonine IRS2 |insulinreceptorsubstrate 2 FOXG1 |forkhead box G1 IRS4 |insulinreceptorsubstrate 4 BRAF |B−Rafproto−oncogene, kinase serine/threonine RAG2 |recombinationactivating 2 MAPK13 |mitogen−activated proteinkinase13 kinase11 STK11 |serine/threonine CCNB3 |cyclinB3 GRM1 |glutamatemetabotropicreceptor1 PRKAB2 |proteinkinaseAMP−activated non−catalyticsubunit beta2 PRKAG2 |proteinkinaseAMP−activated non−catalyticsubunit gamma2 KRAS |proto−oncogene, GTPase PRKAB1 |proteinkinaseAMP−activated non−catalyticsubunit beta1 PRKAG1 |proteinkinaseAMP−activated non−catalyticsubunit gamma1 HOMER3 |homerscaffolding protein3 USP7 |ubiquitinspecificpeptidase7 FBXO25 |F−box protein25 growth factorEGF |epidermal MAPK12 |mitogen−activated proteinkinase12 MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 CREBBP |CREBbindingprotein corepressor likeRBL2 |RBtranscriptional 2 PDPK1 |3−phosphoinositidedependentproteinkinase1 MDM2 |proto−oncogene SMAD4 |SMADfamily member 4 MAPK14 |mitogen−activated proteinkinase14 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha CDK2 |cyclindependentkinase2 SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 BCL6 |B−cellCLL/lymphoma6 FOXO3 |forkhead box O3 STAT3 |signaltransducer andactivator 3 oftranscription MAPK1 |mitogen−activated proteinkinase1 FOXO1 |forkhead box O1 AGAP2 |ArfGAPwithGTPase repeatandPHdomain2 domain,ankyrin PLK4 |pololike kinase4 PTEN |phosphataseandtensinhomolog PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma ARAF |A−Rafproto−oncogene, kinase serine/threonine GABARAPL2 |GABAtypeAreceptorassociatedproteinlike 2 growth factorEGFR |epidermal receptor G6PC3 |glucose−6−phosphatasecatalyticsubunit 3 ATG12 |autophagyrelated12 helix−loop−helixubiquitouskinase CHUK |conserved PLK1 |pololike kinase1 EP300 |E1Abindingproteinp300 TGFBR1 |transforming growth factor betareceptor1 INSR |insulinreceptor CCNB1 |cyclinB1 TGFB3 |transforming growth factor beta3 kinase4 STK4 |serine/threonine subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory BCL2L11 |BCL2like 11 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta CDKN2D |cyclindependentkinaseinhibitor2D GABARAP |GABAtypeAreceptor−associatedprotein NRAS |proto−oncogene, GTPase MAPK11 |mitogen−activated proteinkinase11 regulatedkinase1 SGK1 |serum/glucocorticoid PRKAA1 |proteinkinaseAMP−activated catalyticsubunit alpha1 CCNB2 |cyclinB2 TGFB2 |transforming growth factor beta2 GRB2 |growth factor receptorboundprotein2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta S1PR4 |sphingosine−1−phosphatereceptor4 TNFSF10 |TNFsuperfamily member10 PLK3 |pololike kinase3 MAPK3 |mitogen−activated proteinkinase3 CDKN2B |cyclindependentkinaseinhibitor2B likeKLF2 |Kruppel factor 2 CCND2 |cyclinD2 TGFBR2 |transforming growth factor betareceptor2 TGFB1 |transforming growth factor beta1 S1PR1 |sphingosine−1−phosphatereceptor1 hsa04068 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 80 and Histogram Color Key 202 0 −2 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC PI3K−Akt signalingpathway
Signal transduction SS available undera GYS2 |glycogensynthase2 GNG4 |Gproteinsubunit gamma4 translation initiationfactorEIF4EBP1 |eukaryotic 4Ebindingprotein1 PRLR |prolactinreceptor subunit Bgamma PPP2R2C |proteinphosphatase2regulatory COL2A1 |collagentypeIIalpha1chain receptor GHR |growth hormone subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory receptor EPOR |erythropoietin LAMA1 |lamininsubunit alpha1 GNG13 |Gproteinsubunit gamma13 kinase2 SGK2 |SGK2,serine/threonine GNB3 |Gproteinsubunit beta3 FGF5 |fibroblast growth factor 5 A2 EFNA2 |ephrin 2 somatomammotropinhormone CSH2 |chorionic FGF4 |fibroblast growth factor 4 IFNB1 |interferon beta1 LPAR3 |lysophosphatidicacidreceptor3 FGF6 |fibroblast growth factor 6 kinase11 STK11 |serine/threonine IFNA21 |interferon alpha21 3 IL3 |interleukin IFNA5 |interferon alpha5 LPAR2 |lysophosphatidicacidreceptor2 TSC2 |TSCcomplex subunit 2 FGF17 |fibroblast growth factor 17 proteinS6kinaseB2 RPS6KB2 |ribosomal 1 GH1 |growth hormone FGF20 |fibroblast growth factor 20 FGF22 |fibroblast growth factor 22 FGF14 |fibroblast growth factor 14 LPAR4 |lysophosphatidicacidreceptor4 EPO |erythropoietin KRAS |proto−oncogene, GTPase FGF19 |fibroblast growth factor 19 CCNE2 |cyclinE2 MLST8 |MTOR associatedprotein,LST8homolog FGF11 |fibroblast growth factor 11 COL24A1 |collagentypeXXIValpha1chain PDGFC |plateletderived growth factor C subunitITGA2 |integrin alpha2 BRCA1 |BRCA1,DNArepairassociated subunit Balpha PPP2R2A |proteinphosphatase2regulatory growth factorEGF |epidermal FGF12 |fibroblast growth factor 12 GNGT1 |Gproteinsubunit gammatransducin 1 subunitITGB8 |integrin beta8 MAP2K2 |mitogen−activated proteinkinase2 CSF3R |colony stimulating factor 3receptor growthNGFR |nerve factor receptor MAP2K1 |mitogen−activated proteinkinase1 FGF9 |fibroblast growth factor 9 ANGPT4 |angiopoietin4 GNG7 |Gproteinsubunit gamma7 corepressorlikeRBL2 |RBtranscriptional 2 PDPK1 |3−phosphoinositidedependentproteinkinase1 GSK3B |glycogensynthasekinase3beta MDM2 |proto−oncogene FGF1 |fibroblast growth factor 1 YWHAE |tyrosine3−monooxygenase/tryptophan 5−monooxygenase activation proteinepsilon CREB5 |cAMPresponsive elementbindingprotein5 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha CDK2 |cyclindependentkinase2 KIT |proto−oncogenereceptortyrosinekinase CCNE1 |cyclinE1 GNB2 |Gproteinsubunit beta2 BAD |BCL2associatedagonistofcelldeath SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 IFNAR1 |interferon alphaandbetareceptorsubunit 1 subunitITGA11 |integrin alpha11 PPP2CA |proteinphosphatase2catalyticsubunit alpha subunitITGA10 |integrin alpha10 YWHAG |tyrosine 3−monooxygenase/tryptophan5−monooxygenase activation proteingamma OSM |oncostatinM FGFR3 |fibroblast growth factor receptor3 FOXO3 |forkhead box O3 GNG5 |Gproteinsubunit gamma5 GNG8 |Gproteinsubunit gamma8 bindingsialoprotein IBSP |integrin MAPK1 |mitogen−activated proteinkinase1 TLR2 |tolllike receptor2 GYS1 |glycogensynthase1 IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma THBS3 |thrombospondin3 PTEN |phosphataseandtensinhomolog PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma BCL2L1 |BCL2like 1 subunit B''gammaPPP2R3C |proteinphosphatase2regulatory growth factorEGFR |epidermal receptor RAC1 |Racfamily smallGTPase 1 G6PC3 |glucose−6−phosphatasecatalyticsubunit 3 RHEB |Rashomolog,mTORC1 binding THBS1 |thrombospondin1 translation initiationfactorEIF4E2 |eukaryotic 4Efamily member2 helix−loop−helixubiquitouskinase CHUK |conserved subunit B'deltaPPP2R5D |proteinphosphatase2regulatory RELA |proto−oncogene, NF−kBsubunit CREB3L2 |cAMPresponsive elementbindingprotein3like 2 GNB1 |Gproteinsubunit beta1 INSR |insulinreceptor JAK2 |Janus kinase2 CRTC2 coactivator |CREBregulatedtranscription 2 MCL1 |MCL1,BCL2family apoptosisregulator CREB3 |cAMPresponsive elementbindingprotein3 PKN1 |proteinkinaseN1 IFNAR2 |interferon alphaandbetareceptorsubunit 2 subunitITGB3 |integrin beta3 5−monooxygenaseYWHAZ |tyrosine3−monooxygenase/tryptophan activation proteinzeta ATF6B |activating factor transcription 6beta MET |proto−oncogene, receptortyrosinekinase PPP2CB |proteinphosphatase2catalyticsubunit beta subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory CDC37 |celldivisioncycle37 BCL2L11 |BCL2like 11 PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta GNB4 |Gproteinsubunit beta4 JAK1 |Janus kinase1 ANGPT2 |angiopoietin2 NRAS |proto−oncogene, GTPase SYK |spleenassociatedtyrosinekinase subunitITGB5 |integrin beta5 regulatedkinase1 SGK1 |serum/glucocorticoid F2R |coagulationfactor IIthrombinreceptor subunit B'beta PPP2R5B |proteinphosphatase2regulatory TNC |tenascinC NFKB1 |nuclear factor kappaBsubunit 1 PKN2 |proteinkinaseN2 PRKAA1 |proteinkinaseAMP−activated catalyticsubunit alpha1 COL5A1 |collagentypeValpha1chain COL5A2 |collagentypeValpha2chain VEGF hsa04151 ; this versionpostedFebruary19,2020. 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CA doi: https://doi.org/10.1101/635243 SLC AMPK signalingpathway
Signal transduction SS available undera SCD |stearoyl−CoA desaturase GYS2 |glycogensynthase2 translation initiationfactorEIF4EBP1 |eukaryotic 4Ebindingprotein1 MLYCD |malonyl−CoA decarboxylase subunit Bgamma PPP2R2C |proteinphosphatase2regulatory STRADB |STE20−relatedkinaseadaptorbeta RAB10 |RAB10,memberRASoncogenefamily subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory 4 PFKFB4 |6−phosphofructo−2−kinase/fructose−2,6−biphosphatase IRS2 |insulinreceptorsubstrate 2 IRS4 |insulinreceptorsubstrate 4 kinase11 STK11 |serine/threonine TSC2 |TSCcomplex subunit 2 ADRA1A |adrenoceptoralpha1A PRKAB2 |proteinkinaseAMP−activated non−catalyticsubunit beta2 proteinS6kinaseB2 RPS6KB2 |ribosomal PRKAG2 |proteinkinaseAMP−activated non−catalyticsubunit gamma2 PRKAB1 |proteinkinaseAMP−activated non−catalyticsubunit beta1 CCNA1 |cyclinA1 PRKAG1 |proteinkinaseAMP−activated non−catalyticsubunit gamma1 musclePFKM |phosphofructokinase, AKT1S1 |AKT1substrate 1 palmitoyltransferaseCPT1C |carnitine 1C ACACA |acetyl−CoAcarboxylase alpha subunit Balpha PPP2R2A |proteinphosphatase2regulatory SCD5 |stearoyl−CoA desaturase 5 STRADA |STE20−relatedkinaseadaptoralpha ULK1 |unc−51like autophagyactivating kinase1 PDPK1 |3−phosphoinositidedependentproteinkinase1 ACACB |acetyl−CoAcarboxylase beta CREB5 |cAMPresponsive elementbindingprotein5 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha RAB2A |RAB2A,memberRASoncogenefamily RAB11B |RAB11B, memberRASoncogenefamily HNF4A |hepatocytenuclear factor 4alpha PPP2CA |proteinphosphatase2catalyticsubunit alpha CAMKK1 |calcium/calmodulindependentproteinkinase1 FOXO3 |forkhead box O3 FOXO1 |forkhead box O1 GYS1 |glycogensynthase1 sensitive type LIPE |lipaseE,hormone PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma subunit B''gammaPPP2R3C |proteinphosphatase2regulatory G6PC3 |glucose−6−phosphatasecatalyticsubunit 3 RAB8A |RAB8A,memberRASoncogenefamily RHEB |Rashomolog,mTORC1 binding CFTR |cysticfibrosistransmembrane conductanceregulator subunit B'deltaPPP2R5D |proteinphosphatase2regulatory CREB3L2 |cAMPresponsive elementbindingprotein3like 2 RAB14 |RAB14,memberRASoncogenefamily INSR |insulinreceptor CRTC2 coactivator |CREBregulatedtranscription 2 CREB3 |cAMPresponsive element bindingprotein3 CAB39 |calciumbindingprotein39 PPP2CB |proteinphosphatase2catalyticsubunit beta subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta CAMKK2 |calcium/calmodulindependentproteinkinase2 subunit B'beta PPP2R5B |proteinphosphatase2regulatory PRKAA1 |proteinkinaseAMP−activated catalyticsubunit alpha1 2 PFKFB2 |6−phosphofructo−2−kinase/fructose−2,6−biphosphatase PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta palmitoyltransferaseCPT1A |carnitine 1A CCNA2 |cyclinA2 3 PFKFB3 |6−phosphofructo−2−kinase/fructose−2,6−biphosphatase PPARG |peroxisome proliferator activated receptorgamma TBC1D1 |TBC1domainfamily member1 hsa04152 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC VEGF signalingpathway
Signal transduction SS available undera MAPKAPK3 |mitogen−activated proteinkinase−activated proteinkinase3 RAC3 |Racfamily smallGTPase 3 SPHK1 |sphingosinekinase1 subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory MAPK13 |mitogen−activated proteinkinase13 subunit B,PPP3R2 |proteinphosphatase3regulatory beta KRAS |proto−oncogene, GTPase PRKCG |proteinkinaseCgamma SHC2 |SHCadaptorprotein2 MAPK12 |mitogen−activated proteinkinase12 MAP2K2 |mitogen−activated proteinkinase2 MAP2K1 |mitogen−activated proteinkinase1 MAPK14 |mitogen−activated proteinkinase14 SPHK2 |sphingosinekinase2 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha subunit B,PPP3R1 |proteinphosphatase3regulatory alpha BAD |BCL2associatedagonistofcelldeath MAPKAPK2 |mitogen−activated proteinkinase−activated proteinkinase2 MAPK1 |mitogen−activated proteinkinase1 PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma RAC1 |Racfamily smallGTPase 1 HSPB1 |heatshockproteinfamily B(small)member1 PPP3CA |proteinphosphatase3catalyticsubunit alpha SRC |proto−oncogene, non−receptortyrosinekinase CDC42 |celldivisioncycle42 subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta NRAS |proto−oncogene, GTPase MAPK11 |mitogen−activated proteinkinase11 VEGFA | vascular endothelialgrowth factor A PLCG2 |phospholipaseCgamma2 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta PLA2G4A |phospholipaseA2groupIVA MAPK3 |mitogen−activated proteinkinase3 PXN |paxillin PRKCB |proteinkinaseCbeta domainreceptor KDR |kinaseinsert RAC2 |Racfamily smallGTPase 2 hsa04370 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC Jak−STAT signalingpathway
Signal transduction SS available undera PRLR |prolactinreceptor receptor GHR |growth hormone 13 receptorsubunitIL13RA1 |interleukin alpha1 subunit 2 PIK3R2 |phosphoinositide−3−kinaseregulatory receptor EPOR |erythropoietin 20receptorsubunitIL20RB |interleukin beta IFNK |interferon kappa 2 somatomammotropinhormone CSH2 |chorionic IFNB1 |interferon beta1 IFNW1 |interferon omega 1 IFNA21 |interferon alpha21 5 IL5 |interleukin SPRED3 |sproutyrelatedEVH1domaincontaining3 3 IL3 |interleukin IFNA5 |interferon alpha5 22 IL22 |interleukin IFNL2 |interferon lambda2 1 GH1 |growth hormone IFNL1 |interferon lambda1 12B IL12B |interleukin 22receptorsubunitIL22RA2 |interleukin alpha2 20 IL20 |interleukin EPO |erythropoietin IFNE |interferon epsilon 5receptorsubunitIL5RA |interleukin alpha CRLF2 |cytokinereceptorlike factor 2 12A IL12A |interleukin 9receptor IL9R |interleukin neurotrophicfactor CNTF |ciliary STAM |signaltransducing adaptormolecule CSF3R |colony stimulating factor 3receptor CREBBP |CREBbindingprotein PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit alpha PIAS1 |proteininhibitorofactivated STAT 1 SOS1 |SOSRas/Racguaninenucleotide exchange factor 1 IFNAR1 |interferon alphaandbeta receptorsubunit 1 OSM |oncostatinM STAT3 |signaltransducer andactivator 3 oftranscription PIAS4 |proteininhibitorofactivated STAT 4 CBL |Cbl proto−oncogene PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit gamma BCL2L1 |BCL2like 1 TYK2 |tyrosinekinase2 11receptorsubunitIL11RA |interleukin alpha EP300 |E1Abindingproteinp300 11 IL11 |interleukin JAK2 |Janus kinase2 IFNGR2 |interferon gammareceptor2 SOCS5 |suppressorofcytokinesignaling5 IFNAR2 |interferon alphaandbetareceptorsubunit 2 subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory SPRED2 |sproutyrelatedEVH1domaincontaining2 10receptorsubunitIL10RB |interleukin beta PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta JAK1 |Janus kinase1 22receptorsubunitIL22RA1 |interleukin alpha1 STAT5B |signaltransducer andactivator 5B oftranscription STAT6 |signaltransducer andactivator 6 oftranscription PTPN6 |proteintyrosinephosphatase, non−receptortype6 SOCS1 |suppressorofcytokinesignaling1 CSF2RB |colony stimulating factor 2receptorbetacommonsubunit GRB2 |growth factor receptorboundprotein2 CSF2RA |colony stimulating factor 2receptoralphasubunit PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta STAT1 |signaltransducer andactivator 1 oftranscription SOCS2 |suppressorofcytokinesignaling2 JAK3 |Janus kinase3 LIF |LIF, 6family interleukin cytokine CCND3 |cyclinD3 OSMR |oncostatinMreceptor STAT5A |signaltransducer andactivator 5A oftranscription 15receptorsubunitIL15RA |interleukin alpha 4receptor IL4R |interleukin IFNGR1 |interferon gammareceptor1 6receptor IL6R |interleukin CCND2 |cyclinD2 SPRY4 |sproutyRTK signalingantagonist4 3receptorsubunitIL3RA |interleukin alpha 2receptorsubunitIL2RG |interleukin gamma hsa04630 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC Signal transduction SS TNF signalingpathway available undera TAB3 |TGF−betaactivated kinase1and MAP3K7bindingprotein3 subunit 2 PIK3R2 |phosphoinositide−3−kinase regulatory PGAM5 |PGAMfamily proteinphosphatase serine/threonine member5,mitochondrial domaincontaining2 NOD2 |nucleotide bindingoligomerization ITCH |itchy E3ubiquitinproteinligase MAPK13 |mitogen−activated proteinkinase13 MAP3K5 |mitogen−activated proteinkinase 5 proteinS6kinaseA5 RPS6KA5 |ribosomal MAPK12 |mitogen−activated proteinkinase12 BAG4 |BCL2associatedathanogene4 MAP2K1 |mitogen−activated proteinkinase1 TNF |tumornecrosisfactor MAPK14 |mitogen−activated proteinkinase14 CREB5 |cAMPresponsive elementbindingprotein5 PIK3CA |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit alpha DNM1L |dynamin1like FADD |Fas associatedviadeathdomain MAPK1 |mitogen−activated proteinkinase1 IKBKG |inhibitorofnuclear factor kappaBkinasesubunit gamma PIK3CG |phosphatidylinositol−4,5−bisphosphate3−kinasecatalytic subunit gamma helix−loop−helixubiquitouskinase CHUK |conserved RELA |proto−oncogene, NF−kBsubunit CREB3L2 |cAMPresponsive elementbindingprotein3like 2 CASP8 |caspase8 metallopeptidase3 MMP3 |matrix 18receptor1 IL18R1 |interleukin CREB3 |cAMPresponsive elementbindingprotein3 MAP2K6 |mitogen−activated proteinkinase6 BCL3 |B−cellCLL/lymphoma3 ATF6B |activating factor transcription 6beta 1beta IL1B |interleukin subunit 5 PIK3R5 |phosphoinositide−3−kinaseregulatory kinase3 RIPK3 |receptorinteracting serine/threonine PIK3CB |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit beta CFLAR |CASP8andFADD like apoptosisregulator FAS |Fas cellsurface deathreceptor kinase1 RIPK1 |receptorinteracting serine/threonine TNFRSF1A |TNFreceptorsuperfamily member1A metallopeptidase14 MMP14 |matrix MAPK11 |mitogen−activated proteinkinase11 CXCL3 |C−X−Cmotifchemokineligand3 NFKB1 |nuclear factor kappaBsubunit 1 MLKL |mixed lineagekinasedomainlike pseudokinase CASP10 |caspase10 PIK3CD |phosphatidylinositol−4,5−bisphosphate3−kinasecatalyticsubunit delta LIF |LIF, 6family interleukin cytokine VCAM1 |vascular celladhesionmolecule1 MAPK3 |mitogen−activated proteinkinase3 CEBPB |CCAAT/enhancer bindingproteinbeta CSF1 |colony stimulating factor 1 MAP3K8 |mitogen−activated proteinkinase8 VEGFC |vascular endothelialgrowth factor C NFKBIA |NFKBinhibitoralpha TNFRSF1B |TNFreceptorsuperfamily member1B metallopeptidase9 MMP9 |matrix ICAM1 |intercellularadhesionmolecule1 CXCL1 |C−X−Cmotifchemokineligand1 JAG1 |jagged1 EDN1 |endothelin1 CCL20 |C−Cmotifchemokineligand20 TNFAIP3 |TNFalphainducedprotein 3 hsa04668 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
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CA doi: https://doi.org/10.1101/635243 SLC Transport andcatabolism SS available undera CLTCL1 heavy |clathrin chainlike 1 AP1G2 |adaptorrelatedproteincomplex 1gamma2subunit diphosphohydrolaseENTPD4 |ectonucleoside triphosphate 4 DNASE2B |deoxyribonuclease 2beta ACP2 |acidphosphatase 2, lysosomal CTSF |cathepsinF AP3B2 |adaptorrelatedproteincomplex 3beta2subunit SUMF1 |sulfatase modifyingfactor 1 SGSH |N−sulfoglucosamine sulfohydrolase ATP6V1H |ATPase V1subunit H H+transporting AP1S1 |adaptorrelatedproteincomplex 1sigmasubunit CLTA lightchainA |clathrin AP3B1 |adaptorrelatedproteincomplex 3beta1subunit AP3D1 |adaptorrelatedproteincomplex 3delta1subunit peptidase NAPSA |napsinAaspartic CTSB |cathepsinB LAPTM4B |lysosomalproteintransmembrane 4beta familySLC11A2 |solutecarrier 11member2 AP1G1 |adaptorrelatedproteincomplex 1gammasubunit ATP6V0C |ATPase V0subunit c H+transporting GGA3 |golgiassociated,gammaadaptinearcontaining,ARFbindingprotein 3 GNPTG |N−acetylglucosamine−1−phosphatetransferase gammasubunit LAMP1 |lysosomalassociatedmembrane protein1 GGA1 |golgiassociated,gammaadaptinearcontaining,ARFbindingprotein 1 ATP6AP1 |ATPase protein1 accessory H+transporting familySLC11A1 |solutecarrier 11member1 LAMP2 |lysosomalassociatedmembrane protein2 ABCA2 |ATP bindingcassettesubfamily Amember2 CTSD |cathepsinD ATP6V0D1 |ATPase V0subunit d1 H+transporting PLA2G15 |phospholipaseA2groupXV SCARB2 |scavenger receptorclassB member2 AP4M1 |adaptorrelatedproteincomplex 4mu 1subunit GLB1 |galactosidasebeta1 CD164 |molecule AP4B1 |adaptorrelatedproteincomplex 4beta1subunit NAGA |alpha−N−acetylgalactosaminidase 1 SORT1 |sortilin CLTC heavy |clathrin chain GUSB |glucuronidasebeta NEU1 |neuraminidase 1 ARSA |arylsulfatase A CLTB lightchainB |clathrin ATP6V0B |ATPase V0subunit b H+transporting MCOLN1 |mucolipin 1 ATP6V0A1 |ATPase V0subunit a1 H+transporting GALNS |galactosamine(N−acetyl)−6−sulfatase CTSE |cathepsinE CLN5 |CLN5,intracellular trafficking protein AP1M2 |adaptorrelatedproteincomplex 1mu 2subunit ARSB |arylsulfatase B IGF2R |insulinlike growth factor 2receptor CD68 |molecule MANBA |mannosidasebeta LAPTM4A |lysosomalproteintransmembrane 4alpha AP1M1 |adaptorrelatedproteincomplex 1mu 1subunit CTSH |cathepsinH HEXB |hexosaminidase subunit beta ASAH1 |N−acylsphingosineamidohydrolase 1 AP3S1 |adaptorrelatedproteincomplex 3sigma1subunit familySLC17A5 |solutecarrier 17member5 IDS |iduronate2−sulfatase CTNS |cystinosin,lysosomalcystinetransporter GAA |glucosidasealpha,acid CTSO |cathepsinO CTSV |cathepsinV TCIRG1 |T−cellimmune regulator1,ATPase V0subunit a3 H+transporting PSAP |prosaposin GLA |galactosidasealpha PPT1 |palmitoyl−protein thioesterase 1 CTSA |cathepsinA DNASE2 |deoxyribonuclease 2,lysosomal CTSL |cathepsinL GM2A |GM2gangliosideactivator 2 NPC2 |NPCintracellular cholesteroltransporter peptidase1 TPP1 |tripeptidyl GNS |glucosamine(N−acetyl)−6−sulfatase LITAF inducedTNFfactor |lipopolysaccharide CD63 |molecule LAMP3 |lysosomalassociatedmembrane protein3 GALC |galactosylceramidase CTSZ |cathepsinZ CTSK |cathepsinK LAPTM5 |lysosomalproteintransmembrane 5 CTSC |cathepsinC Lysosome hsa04142 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which . Count
0 20 and Histogram Color Key 11 −1 V bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade alue
CA doi: https://doi.org/10.1101/635243 SLC Transport andcatabolism SS available undera ATP6V0E2 |ATPase V0subunit e2 H+transporting TUBB3 |tubulin beta3class III ATP6V1C2 |ATPase V1subunit C2 H+transporting TUBB4A |tubulin beta4AclassIVa SEC61A2 |Sec61translocon alpha2subunit ATP6V1F |ATPase V1subunit F H+transporting ATP6V1B1 |ATPase V1subunit B1 H+transporting NOX3 |NADPHoxidase 3 TUBA8 |tubulin alpha8 TUBA1C |tubulin alpha1c RAB5A |RAB5A,memberRASoncogenefamily FCGR2B |Fcfragment ofIgGreceptorIIb DYNC1LI1 chain1 |dyneincytoplasmic1lightintermediate FCAR |Fcfragment ofIgAreceptor TUBAL3 |tubulin alphalike 3 HGS |hepatocytegrowth factor−regulated tyrosinekinasesubstrate ACTG1 |actingamma1 ATP6V1H |ATPase V1subunit H H+transporting subunitITGA2 |integrin alpha2 ATP6V1A |ATPase V1subunit A H+transporting SEC22B |SEC22homologB, vesicle trafficking protein(gene/pseudogene) STX18 |syntaxin18 SEC61A1 |Sec61translocon alpha1subunit NOX1 |NADPHoxidase 1 ATP6V0C |ATPase V0subunit c H+transporting LAMP1 |lysosomalassociatedmembrane protein1 ATP6AP1 |ATPase protein1 accessory H+transporting CALR |calreticulin TLR6 |tolllike receptor6 LAMP2 |lysosomalassociatedmembrane protein2 RILP |Rabinteracting lysosomalprotein ATP6V0D1 |ATPase V0subunit d1 H+transporting FCGR1A |Fcfragment ofIgGreceptorIa ATP6V1B2 |ATPase V1subunit B2 H+transporting ATP6V0E1 |ATPase V0subunit e1 H+transporting OLR1 |oxidized low densitylipoproteinreceptor1 CANX |calnexin TLR2 |tolllike receptor2 THBS3 |thrombospondin3 ATP6V0B |ATPase V0subunit b H+transporting ATP6V0A1 |ATPase V0subunit a1 H+transporting FCGR3B |Fcfragment ofIgGreceptorIIIb DYNC2H1 |dyneincytoplasmic2heavy chain1 RAC1 |Racfamily smallGTPase 1 TUBB2A |tubulin beta2AclassIIa HLA−G |majorhistocompatibilitycomplex, classI,G THBS1 |thrombospondin1 MSR1 |macrophagescavenger receptor1 DYNC1H1 |dyneincytoplasmic1heavy chain1 SCARB1 |scavenger receptorclassBmember1 TUBB4B |tubulin beta4BclassIVb ATP6V1E1 |ATPase V1subunit E1 H+transporting subunitITGB3 |integrin beta3 CLEC7A |C−typelectindomaincontaining7A SEC61G |Sec61translocon gammasubunit RAB7A |RAB7A,memberRASoncogenefamily DYNC1LI2 chain2 |dyneincytoplasmic1lightintermediate STX7 |syntaxin7 ATP6V1C1 |ATPase V1subunit C1 H+transporting TCIRG1 |T−cellimmune regulator1,ATPase V0subunit a3 H+transporting VAMP3 |vesicle associatedmembrane protein3 subunitITGB5 |integrin beta5 RAB7B |RAB7B, memberRASoncogenefamily TUBA4A |tubulin alpha4a CTSL |cathepsinL ACTB |actinbeta MARCO |macrophagereceptorwithcollagenousstructure THBS2 |thrombospondin2 subunitITGAM |integrin alphaM CD14 |molecule NCF2 |neutrophilcytosolicfactor 2 NCF4 |neutrophilcytosolicfactor 4 TUBA1B |tubulin alpha1b RAB5C |RAB5C, memberRASoncogenefamily CORO1A |coronin 1A TFRC |transferrin receptor subunitITGB2 |integrin beta2 C1R |complementC1r TAP2 2,ATP |transporter bindingcassettesubfamily Bmember HLA−C |majorhistocompatibilitycomplex, classI,C C3 |complement CYBB |cytochromeb−245betachain CYBA |cytochromeb−245alphachain MRC1 |mannosereceptorC−type1 TAP1 1,ATP |transporter bindingcassettesubfamily Bmember COLEC12 |collectinsubfamily member12 HLA−E |majorhistocompatibilitycomplex, classI,E HLA−F |majorhistocompatibilitycomplex, classI,F HLA−B |majorhistocompatibilitycomplex, classI,B TUBA1A |tubulin alpha1a subunitITGA5 |integrin alpha5 Phagosome hsa04145 ; this versionpostedFebruary19,2020. CC-BY-NC-ND 4.0Internationallicense The copyrightholderforthispreprint(which .