Changes in the human transcriptome upon vitamin D supplementation

Accepted Manuscript Title: CHANGES IN THE HUMAN TRANSCRIPTOME UPON VITAMIN D SUPPLEMENTATION Authors: Yvonne Pasing, Christopher Graham Fenton, Rolf Jorde, Ruth Hracky Paulssen PII: DOI: Reference:

S0960-0760(17)30081-X http://dx.doi.org/doi:10.1016/j.jsbmb.2017.03.016 SBMB 4916

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Journal of Steroid Biochemistry & Molecular Biology

Received date: Revised date: Accepted date:

22-8-2016 25-2-2017 18-3-2017

Please cite this article as: Yvonne Pasing, Christopher Graham Fenton, Rolf Jorde, Ruth Hracky Paulssen, CHANGES IN THE HUMAN TRANSCRIPTOME UPON VITAMIN D SUPPLEMENTATION, Journal of Steroid Biochemistry and Molecular Biologyhttp://dx.doi.org/10.1016/j.jsbmb.2017.03.016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

CHANGES IN THE HUMAN TRANSCRIPTOME UPON VITAMIN D SUPPLEMENTATION Yvonne Pasing1,2, Christopher Graham Fenton3,4, Rolf Jorde1,2 and Ruth Hracky Paulssen3,4 1

Tromsø Endocrine Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT – The Arctic University of Norway, Tromsø, Norway 9037 2

Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway

3

Genomics Support Center Tromsø (GSCT), Department of Clinical Medicine, Faculty of Health Sciences, UiT – The Arctic University of Norway, Tromsø, Norway 9037 4

Gastroenterology and Nutrition Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT – The Arctiv University of Norway, Tromsø, Norway 9037 Corresponding author: Yvonne Pasing, Department of Clinical Medicine, Faculty of Health Sciences, UiT – The Arctic University of Norway, NO-9037 Tromsø, Norway, E-Mail: [email protected],25(OH)2D - 1,25dihydroxyvitamin D 25(OH)D - 25-hydroxyvitamin D PANTHER - Protein Analysis through Evolutionary Relationships PCA - Principal component analysis PLS - Partial least square regression analysis RCT - Randomized controlled trial VDR - Vitamin D receptor Highlights: -

Gene expression analysis of 94 subject after long term RCT Stronger effect of supplementation on the gene expression in women Connection between vitamin D level and gene regulation Influence of vitamin D on immune system, oxidative stress, apoptosis and reproduction 72 novel genes influenced by vitamin D were identified

Abstract Vitamin D is hydroxylated in the liver and kidneys to its active form, which can bind to the vitamin D receptor (VDR). The VDR is present in a wide variety of different cells types and tissues and acts as a transcription factor. Although activation of the VDR is estimated to regulate expression of up to 5 % of the human genome, our study is the first analysing gene expression after supplementation in more than 10 subjects.

Abbreviations: GSEA - Gene Set Enrichment Analysis

Keywords: Apoptosis; ; ; ; ; , gene expression, fertility, immune system, oxidative stress, vitamin D Subjects of a randomized controlled trial (RCT) received either vitamin D3 (n = 47) in a weekly dose of 20,000 IU or placebo (n = 47) for a period of three to five years. For this study, blood samples for preparation of RNA were drawn from the subjects and mRNA gene expression in blood was determined using microarray analysis. The two study groups were similar regarding gender, age, BMI and duration of supplementation, whereas the mean serum 25-hydroxyvitamin D (25(OH)D) level as expected was significantly higher in the vitamin D group (119 versus 63 nmol/L). When analysing all subjects, nearly no significant differences in gene expression between the two groups were found. However, when analysing men and women separately, significant effects on gene expression were observed for women. Furthermore, when only including subjects with the highest and lowest serum 25(OH)D levels, additional vitamin D regulated genes were disclosed. Thus, a total of 99 genes (p<0.05, log2 fold change≥|0.2|) were found to be regulated, of which 72 have not been published before as influenced by vitamin D. These genes were particularly involved in the interleukin signalling pathway, oxidative stress response, apoptosis signalling pathway and gonadotropin releasing hormone receptor pathway. Thus, our results open the possibility for many future studies.

1. Introduction Vitamin D is fat-soluble and generated in the skin upon UV-radiation, but can also be obtained through the diet. It is well established that vitamin D plays a major role in calcium homeostasis and bone mineralization, and that insufficient vitamin D intake can lead to skeletal diseases like rickets in children and osteomalacia in adults [1]. Several cross-sectional studies have found correlations between vitamin D deficiency and autoimmune diseases, different cancer types, infections, cardiovascular diseases, depression, mortality and obesity [2-7]. Nevertheless, the role and functions of vitamin D in the human body are not yet fully understood [8]. Vitamin D insufficiency or deficiency is estimated to be a widespread pandemic [9] affecting approximately 40% of the European population [10]. However, these data are of very variable quality hence estimations might by highly biased [11]. After generation in the skin upon UV-radiation, vitamin D is hydroxylated in the liver to 25hydroxyvitamin D (25(OH)D), which is the storage form of vitamin D and target for analyzing a person’s vitamin D status. Next to diet and sun exposure, adiposity, age, skin colour, genetic and epigenetic factors account for differences in 25(OH)D levels [12]. 25(OH)D is further hydroxylated in the kidneys to its active form 1,25-dihydroxyvitamin D (1,25(OH)2D), which can bind to the vitamin D receptor (VDR). Due to its lipophilic character, 1,25(OH)2D is able to pass through biological membranes, hence gene regulation by vitamin D does not require additional signal transduction steps as those known for hydrophilic signalling molecules, such as peptide hormones, growth factors and cytokines [13]. The VDR is present in a wide variety of different cells types and tissues, and is a member of the nuclear receptor superfamily, known to modulate gene expression by oscillating between on and off states. VDR acts as a transcription factor and its activation is estimated to regulate expression of up to 5 % of the human genome [14], with more than 200 genes estimated to be primary vitamin D targets [15]. Depending on the presence or absence of its ligand, the VDR does not only activate but can also repress gene transcription [16]. Effects of the VDR actions on cell cycling, regulation of growth, proliferation, differentiation, apoptosis, immune system and signalling processes [17] have been reported. Antiproliferative effects of 1,25(OH)2D have been demonstrated in a wide variety of cancer cell lines, including those from prostate, breast, and colon [18]. Furthermore, several studies using chromatin immunoprecipitation combined with high throughput sequencing (ChIP Seq) have reported more than 20,000 genomic VDR binding sites in different human cell lines [19-22]. Many of these are not overlapping, indicating a cell type specific effect of vitamin D. Those studies enable an insight into the diversity and impact of vitamin D on the human transcriptome. Despite the limited knowledge about the effect of vitamin D on the transcriptome, studies analyzing the gene expression in humans in intervention studies are sparse. To our knowledge there is so far only one pilot study, an RCT including eight subjects where the effects of supplementation with vitamin D 400 IU versus 2,000 IU daily for 2 months during the winter were compared on transcriptomic level [23].

The objective of our study was therefore to determine the effect of vitamin D supplementation on the global transcriptomic profile in a larger number of study participants who had received weekly supplementation with 20,000 IU vitamin D3 or placebo over a long period.

2. Material and Methods 2.1 Design of the study The subjects included in the present study all participated in the RCT ”Prevention of type 2 diabetes with vitamin D supplementation in subjects with reduced glucose tolerance” that was performed from March 2008 till May 2015. The design of the main study has been described in detail before [24, 25]. In short, subjects with impaired fasting glucose (IFG) (serum glucose 6.0 – 6.9 mmol/L) and/or impaired glucose tolerance (IGT) (fasting serum glucose <7.0 mmol/L and 2-hour value 7.8 – 11.0 mmol/L at oral glucose tolerance test (OGTT) with 75 g glucose) were included. Subjects with primary hyperparathyroidism, granulomatous disease, history of urolithiasis, cancer diagnosed in the past five years, unstable angina pectoris, myocardial infarction or stroke in the past year were excluded. Pregnant or lactating women, or women of fertile age with no use of contraception, were not included. All visits were performed at the Clinical Research Unit at the University Hospital of North Norway. Fasting blood samples and OGTT were performed annually for a period of five years. Height and weight were measured wearing light clothing. At the first visit the subjects were randomized (non-stratified) in a 1:1 ratio to one capsule vitamin D (cholecalciferol 20,000 IU (Dekristol; Mibe, Jena, Germany)) per week or an identical looking placebo capsule containing arachis oil (Hasco-Lek, Wroclaw, Poland). New medication was supplied every sixth month and unused capsules returned and counted. The subjects were not allowed to take vitamin D supplements (including cod liver oil) exceeding 400 IU per day. If at the annual OGTT the fasting blood glucose was >6.9 mmol/L and/or the 2-h value >11.0 mmol/L the subject was considered to have T2DM, thus ending their participation in the study, and thereafter retested (if necessary) and followed by their general practitioner. From November 2012 HbA1c ≥6.5 % was also included as an additional/alternative diagnostic criterion in accordance with the WHO report from 2011. In addition, if diagnosed elsewhere with T2DM between visits in the study, participation was terminated. As part of the safety monitoring, serum calcium levels were checked at each six months visit. Subjects who developed persistent hypercalcemia (serum calcium >2.55 mmol/L), and subjects who developed renal stones, or symptoms compatible with renal stones were excluded from the study. One subject in the vitamin D group had a serum calcium levels of 2.63 and 2.64 mmol/L at two time points and was therefore excluded from the study. Two subjects in the vitamin D group and one in the placebo group had serum calcium values in the range 2.56 – 2.61 mmol/L that normalized at second testing, hence the subjects continued in the study. In the initial protocol, subjects who during the study were diagnosed with cancer, coronary infarction, unstable angina pectoris, or stroke, were excluded from the study too. From October 2011 this was changed to exclusion of subjects who during the study developed serious disease making it difficult or impossible to attend scheduled visits.

For the present study, subjects who were to come to an annual visit were informed by letter about the sub-study with the consent form enclosed. At the visit they were asked if they wanted to participate, and if so, signed the consent form. In addition, fasting blood samples were drawn in PAXgene Blood RNA tubes (PreAnalytiX), which provide immediate stabilization of intracellular RNA, for later determination of RNA expression. The samples were stored at -70 ̊C until RNA isolation and analysis at the end of the present sub-study. To keep all investigators blinded, all data were sent directly to the Hospital’s Research Department were the data files were merged and coupled to the randomization code. The Research Department then sent the final file without person identification to the principal investigator (R.J.). The study was approved by the Norwegian Medicines Agency (EUDRACTNR – 2007-002167-27) and by the Regional Committee for Medical Research Ethics (REK NORD 2012/626). The trial is registered at ClinicalTrials.gov (NCT01771380). 2.2 Analysis Serum samples for determination of 25(OH)D were frozen until analyzed in batch by an in-house LCMS/MS at the Department of Medical Biochemistry, University Hospital of North Norway [24]. 2.3 RNA preparations Total RNA was isolated from whole blood using the PAXgene Blood RNA Isolation system (Qiagen), and according to the manufacturer's protocol (Qiagen). RNA quantity and purity was assessed by using the NanoDrop ND-1000 spectrophotometer (ThermoFisher Scientific, Wilmington, Delaware, USA). The Experion automated electrophoresis system (BioRad, Hercules, CA, USA) and the RNA StdSens Analysis Kit was used to evaluate RNA integrity, according to the instruction manual. RNA samples were kept at −70°C until further use. RNA samples with RIN >1.8 were used for further analysis. 2.4 Gene Expression Analysis mRNA gene expression was analyzed at a certified Illumina platform at NTNU Genomics Core Facility, Trondheim, Norway. Briefly, RNA was amplified with Ambion`s Illumina® TotalPrep RNA amplification kit (Cat #AMIL 1791) using 150 ng of total RNA as input material. Incorporation of biotin-labeled nucleotides was performed overnight (14 hours) at 37 ˚C in vitro transcription (IVT) amplification that. cRNA was quantified using the NanoDrop ND-1000 (NanoDrop, Wilmington, USA), and cRNA integrity was determined by electrophoresis using the Experion Bioanalyzer (BioRad). A total of 750 ng of biotin-labeled cRNA was hybridized to IlluminaHumanHT-12 v.4 expression bead chip (Illumina®). Beadchips were scanned with Illumina BeadArray Reader. Numerical results were extracted with Bead Studio v3.0.19.0 without any normalization or background subtraction. 2.5 Statistics and Data evaluation Comparisons between the groups were performed with Student´s t-test or chi-square test (p<0.05).

Microarray data analysis was performed using the freely available software R (r-project.org). Raw files where quantile normalized including variance stabilization and background correction using the Bioconductor lumi package (Bioconductor.org). Probes were mapped to gene symbol and genome position

using

the

Bioconductor

illuminaHumanv4.db

package

(http://bioconductor.org/packages/release/data/annotation/html/illuminaHumanv4.db.html).

Probes

with a log2 expression below 7 were removed from the dataset, as the expression level was considered too low to discriminate from background. Descriptive statistics using STATA MP13, were used for comparison of participant groups. Gene expression differences between comparison groups were analyzed using the Limma package (Bioconductor.org). Differentially expressed genes were tested for over-represented

pathways

with

the

GO

hyperGTest

algorithm

in

Kegg

(“http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html”). The data are deposited and accepted

in

GEO

under

accession

number

GSE94138

(https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94138). Enriched genesets were created using Limma differentially regulated probes as input to the Bioconductor GOstats hyperGTest function. Enriched genesets with a p<0.05 were kept. Principal component analysis (PCA) and Partial least squares regression (PLS) [26] were applied on the data in order to visualize the data structure and look for potential outlier samples (https://cran.rproject.org/web/packages/mixOmics/index.html). Gene Set Enrichment Analysis (GSEA) was performed using the R statistical package (http://www.broad.mit.edu/gsea/). Gene Set Enrichment Analysis (GSEA) is a computational method that determines whether an defined set of genes shows statistically significant, concordant differences between two biological states [27]. PANTHER (Protein Analysis through Evolutionary Relationships) Classification System version 10.0 (http://pantherdb.org/) was used for pathway analysis and to classify regulated genes according to their biological function (p<0.05 was considered statistically significant). PANTHER is designed to classify proteins and their genes in order to facilitate high-throughput analysis [28].

3. Results and discussion 3.1 Background variables For the present sub-study, 115 subjects were invited and 94 accepted the invitation, 47 in the vitamin D group and 47 in the placebo group. The two groups did not differ significantly in terms of gender, age, BMI and duration of intervention. There were more smokers among the vitamin D group, but the difference was not statistically significant. At inclusion in the main study the mean serum 25(OH)D levels were similar and as expected, at inclusion in the present sub-study the mean serum 25(OH)D levels were significantly higher in the vitamin D group than the placebo group (119.4 ± 29.1 nmol/L versus 63.4 ± 18.6 nmol/L (p<0.001) (Table 1). 3.2 Gene expression levels in the two study groups The clinical trial included pre-diabetic subjects, but there was no effect on the gene expression in terms of different HbA1c levels of the patients (data not shown). This goes along with the previously published results of the main study, which did not show a protective effect of vitamin D supplementation on the onset of type 2 diabetes [24, 25]. Multivariate data analysis were performed in order to quality assure the gene expression data, and to evaluate if the data were able to separate between subjects receiving vitamin D and those receiving placebo. In a principal component analysis (PCA) women and men could be separated upon their gene expression but no major grouping of the two study groups (vitamin D and placebo) was visible. A partial least square regression analysis (PLS) using serum 25(OH)D levels revealed no further separation between the two groups (data not shown). Although no clear grouping effects were seen, when looking at individual genes, 141 were found to be regulated by vitamin D (p<0.05) with log2 fold changes between |0.04| and |0.40|. In order to quality assure the data we filtered for genes with a log2 fold change of minimum |0.2|, which resulted in five downregulated genes: Formyl peptide receptor 2 (FPR2), CD52 molecule (CD52), interleukin 1 receptor type 2 (IL1R2), G protein subunit gamma 10 (GNG10) and folate receptor 3 gamma (FOLR3). Ribosomal protein S26 (RPS26) was the only upregulated gene. Out of these six genes significantly changed between the vitamin D and the placebo group, only two are to our knowledge published previously as regulated in context with vitamin D (GNG10 [29, 30] and RPS26 [31]). All other regulated genes we found had a log2 fold change of less than |0.2|. Nevertheless could also small changes in gene expression have profound physiological effects. One explanation for the low number of regulated genes could be the high baseline serum 25(OH)D levels in both study groups (~ 61 nmol/L), which indicated that the subjects at inclusion already had a sufficient serum 25(OH)D level, hence a benefit of additional supplementation might be rather unlikely. Furthermore, we were comparing the mRNA levels of two study groups with each other and not the personal change of each subject due to vitamin D supplementation since we just had one sample of each person after long time intervention and not at baseline. This could yield reduced statistical power and leave individual changes undetected. Another explanation could be the long

intervention time, which could reduce the prominence of the gene expression response to vitamin D supplementation. Additionally, detecting small changes in the mRNA is challenging with microarrays, and might be especially so in blood, as its composition is underlying very fast changes and is sensitive to all kind of environmental changes [32]. 3.2.1 Effect of gender Next, we analyzed women and men separately in order to explore if gender could influence the effect of vitamin D on global gene expression. Male participants of both study groups did not separate in either PCA or PLS (Figure 1A and 1B), but there was a grouping for female participants in PCA (Figure 1C) which became more obvious when looking at the corresponding PLS (Figure 1D). For the PLS plots the serum 25(OH)D levels were used as the scoring criteria. The plots indicated an effect of the 25(OH)D level for both men and women, as participants with lower 25(OH)D levels often grouped together with the placebo group, while participants with high 25(OH)D levels grouped separately. It is important to mention, that the female or male vitamin D group did not differ significantly from the corresponding placebo group in terms of physiological characteristics other than serum 25(OH)D level at inclusion in the sub-study (Table 1).

In sum, 58 genes were regulated in men but 3.2 times more (n=185) in women (p<0.05) (supplementary information). After filtering with a log2 fold change of minimum |0.2|, one gene remained regulated in men (interleukin 1 receptor, type II) while 51 remained regulated in women (Tables S2 and S3, supplementary information). Hereby, we could detect for the first time a stronger effect of vitamin D supplementation on gene expression in women when compared to men. An explanation for the differences between women and men might be the in general different serum DBP level between the genders [33], caused most probably by an estrogen-dependent DBP synthesis [34]. Hence, women have higher DBP concentrations and higher serum 25(OH)D concentrations [35] and when embracing also our findings, we assume a possible more important role of vitamin D or more complex regulation mechanisms in women than in men. In order to investigate the regulated genes closer, we performed both pathway analysis and Gene Set Enrichment Analysis (GSEA). Pathway analysis and analysis of biological processes of the 51 regulated genes in women revealed an influence of vitamin D on the interleukin signaling pathway and on genes involved in regulation of sequence-specific DNA binding transcription factor activity, hemopoiesis, B cell mediated immunity and regulation of translation (Table 2). The GSEA of the female data set indicated a major effect of vitamin D supplementation on the immune system, but also on the establishment and/or maintenance of the chromatin architecture, transcription coactivator activity, microtubule cytoskeleton and phosphatidylinositol signaling system (Table S3, supplementary information).

In sum, 51 vitamin D dependent regulated genes in women could be identified (p<0.05, log2 fold change≥|0.2|) of which 38 have to our knowledge not been reported before as regulated upon vitamin D supplementation and thus are interesting for further research on the effect of vitamin D in the human body. For example, the Fas apoptotic inhibitory molecule 3 (FAIM3) was upregulated upon vitamin D supplementation in women. FAIM3 is playing an important role in inflammatory autoimmune responses and protects against death receptor-induced apoptosis by modulating the receptors function [36]. Another example is the observed downregulation of Charcot-Leyden crystal galectin (CLC). This gene is expressed in a variety of tissues and body fluids and is a known marker for allergic inflammation in asthma and allergic rhinitis. However, the role and function of CLC is not entirely understood [37]. 3.2.2 Effect of serum 25(OH)D level for detection of vitamin D dependent changes In another sub-analysis we wanted to investigate if focusing on the subjects with the lowest versus subjects with the highest serum 25(OH)D levels would reveal further effects on the gene expression. For this analysis we included the 20 participants with the lowest (“Bottom 20”, serum 25(OH)D 27 - 59 nmol/L) and the 20 participants with the highest (“Top 20”, serum 25(OH)D 122 – 204 nmol/L) serum 25(OH)D level at inclusion in this sub-study. This number was chosen, as all subjects in the Bottom 20 group received placebo and the group’s average 25(OH)D level is insufficient according to the Institute of Medicine [38], while all subjects in the Top 20 group received vitamin D. Analysis of the background data revealed no significant differences between the study groups except their serum 25(OH)D levels at inclusion in the present sub-study (Table 3).

Interestingly, the expression of 198 mRNAs was differently regulated between these two groups (p<0.05) (supplementary information). This nearly seven times increase compared to the analysis of all 94 subjects supports the hypothesis that a vitamin D threshold exists, above which additional supplementation may not have a major effect [38]. PLS analysis showed clustering of the two study groups (Figure 2), which could not be observed previously when considering all 94 patients (as mentioned in 3.2).

For further evaluation, we filtered the data with a log2 fold change of minimum |0.2| and used the resulting 41 genes (Figure S4 and S5, supplementary information) for analysis of pathways and biological processes (Table 4). To our knowledge, 30 of these genes have not been published before in gene expression studies after vitamin D intervention. As an example, ornithine decarboxylase antizyme 1 (OAZ1) was upregulated in participants with high serum 25(OH)D levels. It has been recently reported that OAZ1 display tumor suppressor activities and has anti-proliferative effects, and influences on cell differentiation and apoptosis [26]. As another example, Granzyme H (GZMH) was downregulated in

those with high serum 25(OH)D. Granzymes have different proteolytic specificities and are potentially able to initiate cell death in tumor and virally infected cells, but so far the biologic functions of GZMH in immune defense cells is hardly understood. In recent studies a high level of GZMH has been found in natural killer cells [39]. Functional analysis of the regulated genes could reveal an influence of vitamin D on three different pathways: oxidative stress response, apoptosis signaling pathway and gonadotropin releasing hormone receptor. Oxidative stress and defective apoptotic processes have been related to several severe diseases in humans like cancer, autoimmune and inflammatory diseases. An influence of vitamin D on both pathways has been implied [40-43], but its role is not fully understood. Gonadotropin releasing hormone receptor plays a major role in controlling the follicular growth, ovulation, corpus luteum maintenance and spermatogenesis, and has been found in cancers of the reproduction system like breast, ovary, endometrium and prostate [44]. In that context it is interesting to note that vitamin D has been suggested to have an influence on fertility and reproduction as VDR and vitamin D metabolizing enzymes were found in reproductive tissues of both women and men [45]. The list of biological processes, which were affected differently in the two study groups, furthermore confirmed the results of our analysis in women, which showed a major effect of vitamin D on the immune system: In summary, we performed gene expression analysis of whole blood samples from 94 participants with prediabetes after supplementation with vitamin D or placebo. The method of testing transcriptomic differences in whole blood does not take tissue specific actions of vitamin D into account, but has the advantage of using peripheral blood as an easily accessible surrogate tissue. The method thereby is of importance to detect and analyze the effects of vitamin D on pathways and biological processes, and could be used to develop and apply a biomarker detection platform. The samples were drawn during a five years lasting RCT with the main goal to evaluate the influence of vitamin D on glucose metabolism and development of type 2 diabetes. At the time of publication, these results were by far the largest RCT on vitamin D supplementation in individuals with prediabetes [24, 25], and also our gene expression analysis is as of today the largest conducted after vitamin D supplementation in humans. We could not separate the vitamin D receiving group form the placebo group with PCA and PLS analysis when all 94 study participants were taken into consideration. Indeed, there were just five mRNAs downregulated and one up-regulated in the vitamin D group compared to the placebo group (p<0.05, log2 fold change ≥|0.2|). However, sub-group analysis could reveal an effect of vitamin D on the gene expression in humans, which was stronger in women than in men, and also more evident when separately evaluating the subjects with the lowest versus the highest serum 25(OH)D levels. A total number of 99 gene (p<0.05, log2 fold change≥|0.2|) were found to be regulated by vitamin D, out of which 72 have

not been published before. However, since these effects were only seen in sub-group analysis of the prediabetic study population, they will be subjects for future studies. In particular, vitamin D showed an influence on the interleukin signaling pathway, oxidative stress response, apoptosis signaling pathway and gonadotropin releasing hormone receptor pathway. In addition, on genes involved in regulation of sequence-specific DNA binding transcription factor activity, hemopoiesis, B cell mediated immunity and regulation of translation, as well as the immune system, establishment and/or maintenance of the chromatin architecture, transcription coactivator activity, microtubule cytoskeleton and phosphatidylinositol signaling system.

Funding This study was supported by grants from The North Norway Regional Health Authority, The Norwegian Diabetes Association, The University of Tromsø, The Research Council of Norway, and The Novo Nordisk foundation. The authors have declared no conflict of interests.

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34. 35. 36. 37. 38.

39. 40. 41. 42. 43. 44. 45.

Sollid, S.T., et al., No effect of high-dose vitamin D supplementation on glycemic status or cardiovascular risk factors in subjects with prediabetes. Diabetes Care, 2014. 37(8): p. 212331. Tenenhaus, M., La régression PLS : théorie et pratique. 1998, Paris: Editions Technip. x, 254 p. Subramanian, A., et al., Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A, 2005. 102(43): p. 15545-50. Thomas, P.D., et al., PANTHER: a library of protein families and subfamilies indexed by function. Genome Res, 2003. 13(9): p. 2129-41. Baeke, F., et al., The vitamin D analog, TX527, promotes a human CD4+CD25highCD127low regulatory T cell profile and induces a migratory signature specific for homing to sites of inflammation. J Immunol, 2011. 186(1): p. 132-42. Stuckey, A., et al., Integrated genomics of ovarian xenograft tumor progression and chemotherapy response. BMC Cancer, 2011. 11: p. 308. Riek, A.E., J. Oh, and C. Bernal-Mizrachi, Vitamin D regulates macrophage cholesterol metabolism in diabetes. J Steroid Biochem Mol Biol, 2010. 121(1-2): p. 430-3. Dumeaux, V., et al., Deciphering normal blood gene expression variation--The NOWAC postgenome study. PLoS Genet, 2010. 6(3): p. e1000873. Bolland, M.J., et al., Age-, gender-, and weight-related effects on levels of 25-hydroxyvitamin D are not mediated by vitamin D binding protein. Clin Endocrinol (Oxf), 2007. 67(2): p. 25964. Speeckaert, M., et al., Biological and clinical aspects of the vitamin D binding protein (Gcglobulin) and its polymorphism. Clin Chim Acta, 2006. 372(1-2): p. 33-42. Hagenau, T., et al., Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos Int, 2009. 20(1): p. 133-40. Planells-Ferrer, L., et al., FAIMs: more than death-receptor antagonists in the nervous system. J Neurochem, 2016. 139(1): p. 11-21. Lin, T.A., et al., The mRNA level of Charcot-Leyden crystal protein/galectin-10 is a marker for CRTH2 activation in human whole blood in vitro. Biomarkers, 2010. 15(7): p. 646-54. Ross, A.C., et al., The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab, 2011. 96(1): p. 53-8. Fellows, E., et al., Natural killer cell-derived human granzyme H induces an alternative, caspase-independent cell-death program. Blood, 2007. 110(2): p. 544-52. Haas, M.J., et al., Inhibition of endoplasmic reticulum stress and oxidative stress by vitamin D in endothelial cells. Free Radic Biol Med, 2016. 99: p. 1-10. Gabr, S.A., et al., Correlation between vitamin D levels and apoptosis in geriatric patients infected with hepatitis C virus genotype 4. Clin Interv Aging, 2016. 11: p. 523-33. Ke, C.Y., et al., Vitamin D3 Reduces Tissue Damage and Oxidative Stress Caused by Exhaustive Exercise. Int J Med Sci, 2016. 13(2): p. 147-53. Tohari, A.M., X. Zhou, and X. Shu, Protection against oxidative stress by vitamin D in cone cells. Cell Biochem Funct, 2016. 34(2): p. 82-94. McArdle, C.A., Gonadotropin-releasing hormone receptor signaling: biased and unbiased. Mini Rev Med Chem, 2012. 12(9): p. 841-50. Lerchbaum, E. and B. Obermayer-Pietsch, Vitamin D and fertility: a systematic review. Eur J Endocrinol, 2012. 166(5): p. 765-78.

Figure Caption

Figure 1: Multivariate data analysis of microarray data from subject after vitamin D (red) or placebo (blue) supplementation. The size of the data spots correlates with the 25(OH)D level. (A) PCA women, (B) PCA men, (C) PLS regression women, and (D) PLS regression men. 25(OH)D level was used as the scoring vector for PLS analysis. In both female and male PCA, principle component 1 (PC1) accounted for more than 90% of explained variance.

Figure 2: Partial-least-square regression analysis of the gene expression data of the 20 subject with the highest 25(OH)D level after vitamin D supplementation (red) and the 20 subject with the lowest 25(OH)D level after placebo supplementation (blue). The size of the data spots correlates with the 25(OH)D level. Circles represent female participants and squares male participants. Serum 25(OH)D level was used as the PLS scoring vector.

Table 1: Background data of the study participants (n=94)

Vitamin D group

Placebo group

All

Men

Women

All

Men

Women

n = 47

n = 29

n = 18

n = 47

n = 35

n = 12

Women/Men [%]

38.3/61.7

0/100

100/0

25.5/74.5

0/100

100/0

Age at inclusion in present

61.0

61.0

61.1

62.3

61.0

65.8

sub-study [years]

(± 8.5)

(± 7.7)

(± 9.9)

(± 8.6)

(± 8.1)

(± 9.4)

BMI at inclusion in present

29.0

28.8

29.3

28.90

29.5

27.1

sub-study [kg/m2]

(± 3.8)

(± 3.8)

(± 3.9)

(± 3.9)

(± 3.0)

(± 5.4)

Duration of intervention

50.6

49.1

52.9

49.8

47.4

56.7

[month]

(± 8.4)

(± 9.5)

(± 5.9)

(± 9.7)

(± 9.8)

(±5.5)

Serum 25(OH)D at inclusion

61.4

61.4

61.5

61.9

59.4

69.1

in main study [nmol/L]

(± 27.4)

(± 31.3)

(± 20.4)

(± 19.2)

(± 16.3)

(± 25.3)

Serum 25(OH)D at inclusion

119.5*

119.6**

119.3***

63.4*

62.6**

65.7***

in present sub-study [nmol/L]

(± 29.1)

(± 28.7)

(± 30.6)

(± 18.6)

(± 19.9)

(± 14.8)

Smoking status at inclusion in

21.3

20.7

22.2

8.5

5.7

16.7

present sub-study [%] *,**, *** Student´s t-test (p<0.01)

Table 2: Panther analysis of the 51 regulated genes in women (n=30) Hits Expected (48) Hits PANTHER Pathways Interleukin signaling pathway (P00036) 2 0.22 PANTHER GO-Slim Biological Process Regulation of sequence-specific DNA binding 1 0.03 transcription factor activity (GO:0051090) Hemopoiesis (GO:0030097) 2 0.26 B cell mediated immunity (GO:0019724) 2 0.33 Regulation of translation (GO:0006417) 2 0.34

Fold Enrichment

P-value

>5

2.13E-02

>5

3.40E-02

>5 >5 >5

2.77E-02 4.21E-02 4.60E-02

Table 3: Background data of the study participants (n=40) with Bottom 20 and Top 20 serum 25(OH)D levels Bottom 20 Top 20

Women/Men [%]

15/85

40/60

Age at inclusion in present sub-study [years]

61 (± 10)

63 (± 9.2)

BMI at inclusion in present sub-study [kg/m2]

34.3 (± 2.7)

36.1 (± 4.7)

Duration of intervention [month]

50.6 (± 9.6)

51.5 (± 7.8)

Serum 25(OH)D at inclusion in main study

54.4 (± 14.3)

67.9 (± 36.6)

47.4 (± 10.6)*

145.4 (± 22.1)*

10

30

[nmol/L] Serum 25(OH)D at inclusion in present sub-study [nmol/L] Smoking at inclusion in present sub-study [%] * Student´s t-test (p<0.01)

Table 4: Panther analysis of the 41 regulates genes between the Bottom 20 and Top 20 group (n=40) Hits Expected Fold Hits Enrichment PANTHER Pathways Oxidative stress response (P00046) 1 0.05 >5 Apoptosis signaling pathway (P00006) 2 0.21 >5 Gonadotropin releasing hormone receptor pathway 3 0.41 >5 (P06664) PANTHER GO-Slim Biological Process Protein methylation (GO:0006479) 1 0.03 >5 Negative regulation of apoptotic process 2 0.17 >5 (GO:0043066) Natural killer cell activation (GO:0030101) 2 0.18 >5 B cell mediated immunity (GO:0019724) 2 0.26 >5 Regulation of phosphate metabolic process 2 0.32 >5 (GO:0019220) Immune response (GO:0006955) 5 0.95 >5 Translation (GO:0006412) 4 0.79 >5 Immune system process (GO:0002376) 11 2.54 4.33 Apoptotic process (GO:0006915) 4 1 4 Cell death (GO:0008219) 4 1.03 3.9 Death (GO:0016265) 4 1.03 3.87 Response to stimulus (GO:0050896) 12 3.96 3.03 Protein metabolic process (GO:0019538) 11 4.91 2.24 Regulation of biological process (GO:0050789) 10 5.2 1.92

ILMN_2217935 ILMN_2366790 ILMN_1776963 ILMN_2087528 ILMN_1667716 ILMN_2385688 ILMN_1673962 ILMN_1764043 ILMN_3199647 ILMN_1746457 ILMN_3236244 ILMN_2352609 ILMN_1767651 ILMN_1675612 ILMN_1798288 ILMN_1794825 ILMN_1661594 ILMN_1708143

P-value

4.81E-02 1.88E-02 8.04E-03

2.52E-02 1.31E-02 1.42E-02 2.75E-02 4.20E-02 2.42E-03 7.99E-03 2.62E-05 1.74E-02 1.89E-02 1.93E-02 3.29E-04 7.11E-03 2.83E-02

logFC AveExpr t P.Value adj.P.Val B name symbol -0.04133856006 8.1515435 -2.124330 0.0362310 0.0497372 -3.692546 replicatio RFC1 -0.04832125383 8.3606079 -2.183417 0.0314605 0.0497372 -3.585801 DEAD-box DDX52 0.049298448132 8.2662464 2.0552422 0.0425918 0.0497372 -3.814018 lectin, ma LMAN2 -0.05015810177 8.9530944 -2.031473 0.0449916 0.0497372 -3.854970 cleavage CPSF3 -0.05090265932 8.5944643 -1.988995 0.0495691 0.0499766 -3.927078 transmem TMEM101 -0.05265512075 8.2965260 -2.101042 0.0382766 0.0497372 -3.733896 RAB, me RABL2B -0.05267177973 8.4854731 -2.118888 0.0367004 0.0497372 -3.702246 nucleopor NUP205 0.052802174354 8.2697725 2.1272896 0.0359780 0.0497372 -3.687263 tubulin ty TTL 0.053451697531 8.3779295 2.0215016 0.0460324 0.0497372 -3.872021 chromobo CBX1 -0.05429847594 9.0694468 -2.116398 0.0369169 0.0497372 -3.706676 general tr GTF3C2 0.054351642563 8.7071443 2.5185244 0.0134508 0.0497372 -2.931769 chromoso C1orf174 0.054442210558 8.0291873 2.3014130 0.0235470 0.0497372 -3.364851 8-oxogua OGG1 -0.05475051990 8.0685256 -2.018440 0.0463559 0.0497372 -3.877240 tectonin b TECPR1 -0.05491506260 8.1967310 -2.236764 0.0276334 0.0497372 -3.487185 bladder c BLCAP 0.055268303095 9.1526636 2.0378209 0.0443397 0.0497372 -3.844075 MOB kina MOB3C -0.05581366955 8.3143574 -2.285782 0.0244829 0.0497372 -3.394711 aldehyde ALDH3A2 -0.05583440717 8.3941699 -2.386019 0.0190087 0.0497372 -3.200126 chromoso C2orf42 -0.05593834344 8.4027326 -2.013004 0.0469354 0.0497372 -3.886492 family wit FAM127A

ILMN_2066348 ILMN_1843932 ILMN_1673252 ILMN_1723177 ILMN_2208495 ILMN_3222974 ILMN_1811574 ILMN_1688629 ILMN_2151441 ILMN_1660199 ILMN_1697420 ILMN_2076250 ILMN_1768391 ILMN_2212354 ILMN_1798659 ILMN_1732300 ILMN_2356031 ILMN_1703866 ILMN_1664956 ILMN_1759341 ILMN_2326997 ILMN_1812856 ILMN_1696065 ILMN_3246900 ILMN_3228639 ILMN_2391355 ILMN_1719656 ILMN_1804610 ILMN_1665982 ILMN_2363668 ILMN_3201517 ILMN_3244434 ILMN_1815733 ILMN_1708081 ILMN_1755589 ILMN_1742577 ILMN_2082810 ILMN_1751871 ILMN_1756860 ILMN_1810559 ILMN_1671494 ILMN_1730824 ILMN_1795474 ILMN_1838313 ILMN_1765326

-0.05659217389 8.3658286 -2.041471 0.0439684 0.0497372 -3.837797 HERPUD f HERPUD2 0.057095900940 8.1916187 2.4393353 0.0165647 0.0497372 -3.093658 SAP30-lik SAP30L 0.057516198209 8.9061092 2.0128044 0.0469568 0.0497372 -3.886831 aminoacyl AIMP2 -0.05761569231 9.6379018 -2.222733 0.0285983 0.0497372 -3.513329 anaphase ANAPC5 0.058006753382 8.2595157 2.1824091 0.0315372 0.0497372 -3.587645 ceramide CERS5 0.058807485919 8.1296113 2.1225757 0.0363818 0.0497372 -3.695676 protein ki PRKCB -0.06026305880 8.7385665 -2.067930 0.0413564 0.0497372 -3.791981 mitogen- MAPK8IP3 0.060524195944 8.4748035 2.1530387 0.0338402 0.0497372 -3.641011 zinc finge ZNF274 -0.06105080688 8.5996358 -2.077434 0.0404514 0.0497372 -3.775395 family wit FAM103A1 -0.06184455583 8.3154818 -2.413998 0.0176888 0.0497372 -3.144508 acetyl-Co ACAA2 0.062367519862 10.125959 2.4447544 0.0163327 0.0497372 -3.082722 TERF1 (TR TINF2 -0.06240175129 8.1267543 -2.298070 0.0237444 0.0497372 -3.371252 GC-rich pr GPBP1L1 0.062512494587 8.1192004 2.1895442 0.0309987 0.0497372 -3.574584 ADP ribos ARL4C -0.06271099795 8.0124995 -2.413959 0.0176906 0.0497372 -3.144587 WD repea WDR46 0.063230559877 9.4621202 2.3008347 0.0235810 0.0497372 -3.365959 coiled-coi CCDC28A -0.06337211132 8.0751316 -2.762496 0.0068838 0.0497372 -2.405430 polymera POLR2C -0.06358189484 8.0613430 -2.613143 0.0104259 0.0497372 -2.732531 ring finge RNF121 -0.06378170376 8.1378636 -1.989710 0.0494889 0.0499766 -3.925875 SPT5 hom SUPT5H -0.06406550841 10.560606 -2.189164 0.0310272 0.0497372 -3.575279 SSU72 ho SSU72 -0.06408782865 8.2291936 -2.184174 0.0314032 0.0497372 -3.584417 mannosid MAN2B1 -0.06444547981 9.4920319 -2.231916 0.0279635 0.0497372 -3.496234 deoxyhyp DHPS -0.06483255935 8.4818908 -2.105893 0.0378424 0.0497372 -3.725315 zinc finge ZSWIM1 -0.06523831207 8.4460925 -2.557635 0.0121159 0.0497372 -2.850174 stromal c SDF4 -0.06534685888 8.0336363 -2.109712 0.0375037 0.0497372 -3.718549 long inter LINC01278 0.065470904450 8.6799686 2.0312213 0.0450177 0.0497372 -3.855401 NA NA 0.065782636799 8.1158217 2.6576838 0.0092271 0.0497372 -2.636584 STAM bin STAMBP -0.06635614349 8.1460404 -2.089916 0.0392886 0.0497372 -3.753506 mitochon MRPL38 -0.06635617457 8.7268713 -2.195142 0.0305819 0.0497372 -3.564308 nuclear tr NFX1 -0.06687598658 8.0295644 -2.204077 0.0299268 0.0497372 -3.547862 AKT inter AKTIP -0.06713039271 8.9504885 -2.062051 0.0419249 0.0497372 -3.802207 Yip1 inter YIF1B -0.06716132734 13.297021 -2.160148 0.0332697 0.0497372 -3.628151 ribosomal RPL23AP64 0.067416986103 8.0355304 2.5324173 0.0129622 0.0497372 -2.902909 ArfGAP wi ARAP2 0.067858601335 8.6280101 2.1983150 0.0303479 0.0497372 -3.558476 eukaryoti EIF5 -0.06818580867 8.1937230 -2.001789 0.0481504 0.0499766 -3.905505 lysocardio LCLAT1 0.068553631773 8.1943366 2.0519200 0.0429205 0.0497372 -3.819768 disco inte DIP2B -0.06881197167 9.1140432 -2.074522 0.0407268 0.0497372 -3.780483 GTP bindi GTPBP4 -0.06989222445 8.6456826 -2.215635 0.0290975 0.0497372 -3.526497 bromodo BRD7 -0.06999920842 8.0190388 -2.047152 0.0433959 0.0497372 -3.828003 serine/thr STK11 -0.07051949437 8.2750853 -2.039682 0.0441500 0.0497372 -3.840875 thioredox TXNL1 0.070926657370 9.9936864 2.1612901 0.0331788 0.0497372 -3.626083 ras homol RHOQ -0.07131193055 8.5169378 -2.072120 0.0409553 0.0497372 -3.784677 ubiquitin USP5 -0.07143569562 8.8597062 -2.119172 0.0366757 0.0497372 -3.701740 zinc finge ZNF512 -0.07150436811 8.8294576 -2.294765 0.0239411 0.0497372 -3.377573 chaperoni CCT8 0.072172806306 8.0988340 2.1493026 0.0341433 0.0497372 -3.647752 leucine-ri LRRC8B -0.07224013951 8.7130509 -2.353023 0.0206770 0.0497372 -3.264987 diacylglyc DGKD

ILMN_1661264 ILMN_1718706 ILMN_1663512 ILMN_1760922 ILMN_1769027 ILMN_1720819 ILMN_2311537 ILMN_1867439 ILMN_1775074 ILMN_2408645 ILMN_2278433 ILMN_2415189 ILMN_2073157 ILMN_1748625 ILMN_1713752 ILMN_1772876 ILMN_1780382 ILMN_3248403 ILMN_1728684 ILMN_1674941 ILMN_1753112 ILMN_1699991 ILMN_1753468 ILMN_1663489 ILMN_1768719 ILMN_1668743 ILMN_2374164 ILMN_1720542 ILMN_1658995 ILMN_3240586 ILMN_2376205 ILMN_1675156 ILMN_1783226 ILMN_1756204 ILMN_1751656 ILMN_1808395 ILMN_1795400 ILMN_1763147 ILMN_1731001 ILMN_1675848 ILMN_1917290 ILMN_2366634 ILMN_1686626 ILMN_1758823 ILMN_2091412

-0.07237900443 9.1570803 -2.013974 0.0468315 0.0497372 -3.884842 serine hy SHMT2 -0.07277365028 8.4580315 -2.226249 0.0283538 0.0497372 -3.506791 Era-like 1 ERAL1 0.074142602246 10.851040 2.3303646 0.0218965 0.0497372 -3.309071 cytochro COX5B 0.074553172608 8.1513444 2.3968605 0.0184872 0.0497372 -3.178643 G protein- GIT2 -0.07572647090 8.4304654 -1.993512 0.0490643 0.0499766 -3.919476 CDC42 sm CDC42SE1 0.076160482181 9.9259256 2.6045818 0.0106718 0.0497372 -2.750817 NA NA -0.07648211151 8.4240185 -2.216831 0.0290129 0.0497372 -3.524281 high mobi HMGA1 0.076878404059 8.0384181 2.5297750 0.0130539 0.0497372 -2.908408 NA NA -0.07733478874 8.2931048 -2.579354 0.0114273 0.0497372 -2.804399 tubulin ga TUBGCP2 0.078347790755 8.4877733 2.1763463 0.0320011 0.0497372 -3.598714 NA NA 0.078660985776 8.9693586 2.0741257 0.0407645 0.0497372 -3.781176 anaphase LOC285074 -0.07874633522 9.8785891 -2.129817 0.0357631 0.0497372 -3.682744 ATPase N ATP1A1 -0.07895720192 8.0182757 -2.079354 0.0402706 0.0497372 -3.772035 amylase, AMY2B -0.07937224448 8.3675192 -2.562354 0.0119632 0.0497372 -2.840257 transcripti TCEAL4 -0.07986232282 8.0188379 -2.758831 0.0069556 0.0497372 -2.413640 serine inc SERINC3 -0.08039876910 8.5665405 -2.465424 0.0154742 0.0497372 -3.040817 zinc finge ZNF395 0.080953113731 8.7627484 2.3766795 0.0194683 0.0497372 -3.218566 signal pep SPCS2P4 0.080988239899 8.4271294 2.5861403 0.0112194 0.0497372 -2.790030 succinate SDHC -0.08112557565 8.2570470 -2.331800 0.0218174 0.0497372 -3.306288 proline, gl PELP1 0.081200306238 8.3255910 2.2832617 0.0246368 0.0497372 -3.399510 anoctami ANO6 -0.08331698884 8.1142363 -2.022469 0.0459304 0.0497372 -3.870369 CD5 mole CD5 -0.08408495643 8.1818982 -2.254645 0.0264452 0.0497372 -3.453658 LCK proto LCK 0.084272255599 9.7551519 2.1804901 0.0316834 0.0497372 -3.591152 CD63 mol CD63 0.084417841412 8.9130395 2.1468413 0.0343444 0.0497372 -3.652188 ubiquitin UBR2 -0.08542648347 9.7171592 -2.937763 0.0041458 0.0497372 -2.002409 retinol de RDH11 0.086886926343 9.3619404 2.3626795 0.0201758 0.0497372 -3.246088 Rab intera RILPL2 0.088220529629 9.5038490 2.4498943 0.0161154 0.0497372 -3.072330 homocyst HERPUD1 -0.08859400971 8.0532538 -2.490279 0.0144955 0.0497372 -2.990022 polymera POLR2I 0.088755325213 8.2670209 2.4456176 0.0162960 0.0497372 -3.080978 acyl-CoA t ACOT9 -0.08886917360 8.0509358 -2.104618 0.0379561 0.0497372 -3.727573 phospholi PLD6 -0.09051556604 12.185408 -2.067915 0.0413578 0.0497372 -3.792007 lymphoto LTB 0.090555926214 8.0395609 2.2242221 0.0284946 0.0497372 -3.510561 cell divisi CDC42 0.090641575449 9.4542764 2.1592679 0.0333399 0.0497372 -3.629746 signal seq SSR2 -0.09090038714 8.5987405 -2.873377 0.0050070 0.0497372 -2.152826 ribosomal RPS6KA4 0.091044745893 8.4968991 2.3443011 0.0211391 0.0497372 -3.282001 Kruppel-li KLF11 -0.09122915382 8.8758214 -2.178905 0.0318045 0.0497372 -3.594045 ArfGAP wi ACAP1 -0.09157685144 8.6328206 -2.114196 0.0371092 0.0497372 -3.710590 tubulin fo TBCD 0.091758927205 9.0545354 2.3499226 0.0208403 0.0497372 -3.271042 NADH:ubi NDUFB6 0.091998964627 8.4992431 2.4457910 0.0162887 0.0497372 -3.080627 glutamate ERICH1 -0.09246828452 12.087984 -2.094360 0.0388816 0.0497372 -3.745684 myosin lig MYL12A 0.093086516453 8.1926617 2.4438280 0.0163722 0.0497372 -3.084593 lysosomal LAMP2 -0.09338644755 8.9057440 -2.092571 0.0390450 0.0497372 -3.748834 pyruvate PKM -0.09586947662 10.259660 -2.108944 0.0375716 0.0497372 -3.719911 NA NA -0.09940908170 8.3404257 -2.457812 0.0157856 0.0497372 -3.056284 SWI/SNF r SMARCB1 -0.10077971002 8.3791122 -2.103941 0.0380166 0.0497372 -3.728770 fms relate FLT3LG

ILMN_1700432 ILMN_1733311 ILMN_1803988 ILMN_1712944 ILMN_3308936 ILMN_1803676 ILMN_1813240 ILMN_1678490 ILMN_2377240 ILMN_2371590 ILMN_2333594 ILMN_1712305 ILMN_2349138 ILMN_3228294 ILMN_1793990 ILMN_1746436 ILMN_2376204 ILMN_2232478 ILMN_2359945 ILMN_1776515 ILMN_3246910 ILMN_1657129 ILMN_2384181 ILMN_3214893 ILMN_3248324 ILMN_3306672 ILMN_1805377 ILMN_1688231 ILMN_1785424 ILMN_1781285 ILMN_1679268 ILMN_2276952 ILMN_1675939 ILMN_1768505 ILMN_1844464 ILMN_1692956 ILMN_1760347 ILMN_2376403 ILMN_1760374 ILMN_1795243 ILMN_1740875 ILMN_1778444 ILMN_2392569 ILMN_2208903 ILMN_1772131

-0.10133173546 8.6392986 -2.281988 0.0247149 0.0497372 -3.401932 inositol-tr ITPKB 0.101464597361 8.5046510 2.0846204 0.0397784 0.0497372 -3.762807 phosphati PIGB 0.102518640316 11.245825 2.2672498 0.0256348 0.0497372 -3.429882 myeloid c MCL1 -0.10324398497 10.246553 -2.038181 0.0443029 0.0497372 -3.843456 amino-ter AES 0.103447602136 8.1056297 2.6025344 0.0107314 0.0497372 -2.755182 microRNA MIR223 -0.10396632693 8.0386437 -2.285086 0.0245253 0.0497372 -3.396037 enolase s ENOSF1 -0.10665229767 8.3052043 -2.288420 0.0243227 0.0497372 -3.389684 eukaryoti EIF1AX 0.106863625386 9.0334365 2.5583316 0.0120933 0.0497372 -2.848712 Rab intera RILPL2 -0.10901716669 8.7939496 -2.704512 0.0081028 0.0497372 -2.534234 AKT inter AKTIP -0.10986031724 10.684115 -2.290466 0.0241990 0.0497372 -3.385782 DEAD-box DDX17 0.112677404351 9.6099177 2.0835229 0.0398805 0.0497372 -3.764732 small ubi SUMO2 0.113397308583 8.3376749 2.1863088 0.0312419 0.0497372 -3.580511 cytochro CYBRD1 -0.11471214621 9.7620491 -2.129346 0.0358030 0.0497372 -3.683586 CDC42 sm CDC42SE1 -0.11647131927 11.041643 -2.453057 0.0159829 0.0497372 -3.065924 ribosomal RPL28 0.116679221142 9.2493036 2.3407525 0.0213298 0.0497372 -3.288907 inhibitor ID2 0.118932518149 9.0938315 2.0353158 0.0445960 0.0497372 -3.848378 HLA comp HCG27 -0.12081812090 10.230282 -2.283791 0.0246044 0.0497372 -3.398501 lymphoto LTB 0.122370749861 8.8127785 2.4612800 0.0156430 0.0497372 -3.049243 apolipopr APOBEC3G 0.123452435672 8.0304286 1.9992129 0.0484333 0.0499766 -3.909860 carboxyle CES1 0.124867729567 8.9190338 2.7517159 0.0070969 0.0497372 -2.429551 metallop MPPE1 -0.12826738886 9.5970525 -1.985379 0.0499766 0.0499766 -3.933153 uncharact LOC100190986 0.128698025609 9.0634700 2.1285478 0.0358709 0.0497372 -3.685014 src kinase SKAP2 0.130844395684 8.4388758 2.0431713 0.0437964 0.0497372 -3.834869 dehydrog DHRS9 0.132681875938 8.6202919 2.2363107 0.0276642 0.0497372 -3.488033 NA NA 0.137352761157 8.5164603 2.7727601 0.0066863 0.0497372 -2.382394 NA NA 0.143784463788 8.2902521 2.4422180 0.0164409 0.0497372 -3.087843 protein as PATL2 -0.14563979252 8.3894644 -2.220984 0.0287206 0.0497372 -3.516576 NA NA 0.149579622801 8.1995457 2.5758588 0.0115357 0.0497372 -2.811789 triggering TREM1 -0.15003865876 9.6574539 -2.120039 0.0366006 0.0497372 -3.700195 actin bind ABLIM1 0.150651345084 11.440622 2.1093481 0.0375359 0.0497372 -3.719195 dual speci DUSP1 0.150944647302 9.0817363 2.0468293 0.0434283 0.0497372 -3.828562 pellino E3 PELI1 0.152496818279 8.2874222 2.4078248 0.0179728 0.0497372 -3.156829 TSC22 do TSC22D3 0.153498871299 10.396988 1.9872547 0.0497649 0.0499766 -3.930004 interfero IFNGR1 0.155906465999 10.355329 2.4381361 0.0166164 0.0497372 -3.096075 interleuki IL13RA1 -0.16528155036 11.574590 -2.162947 0.0330474 0.0497372 -3.623080 NA NA -0.16532889547 10.295782 -2.129720 0.0357713 0.0497372 -3.682917 ribosomal RPLP2 0.167464857195 12.596629 2.0090209 0.0473639 0.0498405 -3.893256 serglycin SRGN 0.169486788559 10.989053 2.6011119 0.0107730 0.0497372 -2.758213 TSC22 do TSC22D3 0.171146996654 8.1109009 2.7357753 0.0074231 0.0497372 -2.465071 CD8a mol CD8A -0.17920481536 11.761120 -2.364554 0.0200798 0.0497372 -3.242410 ribosomal RPS4X 0.192136489951 9.6035627 2.0829466 0.0399342 0.0497372 -3.765742 formyl pe FPR2 0.195712655450 10.111035 2.9510425 0.0039861 0.0497372 -1.971050 FK506 bin FKBP5 0.201489948462 8.8693663 2.1321524 0.0355655 0.0497372 -3.678566 formyl pe FPR2 0.214457269494 10.557455 2.0911360 0.0391765 0.0497372 -3.751361 CD52 mol CD52 0.224267756857 9.7462693 2.8425247 0.0054755 0.0497372 -2.223936 interleuki IL1R2

ILMN_1757074 ILMN_3291511 ILMN_1657950 ILMN_1695585 ILMN_3248833 ILMN_1730454 ILMN_3242288 ILMN_3285153

0.226776096780 9.0343000 2.0915113 0.0391421 0.0497372 -3.750700 G protein GNG10 -0.23163581841 8.4166927 -2.014893 0.0467333 0.0497372 -3.883278 ribosomal RPS26 -0.23913718974 8.2057506 -2.032809 0.0448538 0.0497372 -3.852680 ribosomal RPS26 -0.37267875909 11.557208 -1.988942 0.0495752 0.0499766 -3.927168 ribosomal RPS26 -0.37685736366 9.8334352 -2.072853 0.0408854 0.0497372 -3.783397 ribosomal RPS26 0.399742949547 9.8994990 2.0679286 0.0413566 0.0497372 -3.791984 folate rec FOLR3 -0.42171455474 10.772433 -2.285950 0.0244727 0.0497372 -3.394392 NA NA -0.42631416920 10.662176 -2.245779 0.0270286 0.0497372 -3.470311 NA NA

Probe

logFC

abs(logFC) AveExpr

t

P.Value

B

symbol

name

ILMN_179 0.7092918 0.7092918 9.1023111 3.1300760 0.0037798 -2.353241 CHURC1

churchill domain containing 1

ILMN_226 0.5563773 0.5563773 8.6970519 2.3369610 0.0260410 -3.461458 NA

NA

ILMN_175 0.4724604 0.4724604 8.9412102 2.5260697 0.0168283 -3.211730 GNG10

guanine nucleotide binding pr

ILMN_165 0.4541157 0.4541157 10.111769 2.4081279 0.0221382 -3.368766 CLC

Charcot-Leyden crystal galec

ILMN_172 -0.449323 0.4493232 8.1719300 -2.888775 0.0069773 -2.705593 NA

NA

ILMN_170 0.4236132 0.4236132 9.0608154 2.4160831 0.0217368 -3.358306 IFIT3

interferon-induced protein wit

ILMN_173 0.4116549 0.4116549 9.3093849 2.6314530 0.0131026 -3.068060 DHRS9

dehydrogenase/reductase (SD

ILMN_177 0.4023494 0.4023494 10.096216 2.9449223 0.0060607 -2.624570 FKBP5

FK506 binding protein 5

ILMN_166 0.3925929 0.3925929 8.0474184 2.4411232 0.0205163 -3.325253 IFIT3

interferon-induced protein wit

ILMN_324 0.3790948 0.3790948 8.2022227 2.0676283 0.0470636 -3.796588 FCGR1C

Fc fragment of IgG, high affin

ILMN_223 0.3623863 0.3623863 8.6001417 2.1334926 0.0408622 -3.717061 IFIT3

interferon-induced protein wit

ILMN_237 -0.348644 0.3486447 9.9508693 -2.135560 0.0406798 -3.714538 GRINA

glutamate receptor, ionotropic

ILMN_216 0.3299820 0.3299820 12.868901 2.1880440 0.0362871 -3.649967 SRGN

serglycin

ILMN_168 0.3197895 0.3197895 9.2539908 2.2465463 0.0318945 -3.576822 LAP3

leucine aminopeptidase 3

ILMN_176 0.3179768 0.3179768 12.485173 2.2190780 0.0338938 -3.611316 SRGN

serglycin

ILMN_180 0.3112103 0.3112103 9.3407347 2.7451301 0.0099507 -2.909844 VAMP5

vesicle-associated membrane

ILMN_206 0.3085673 0.3085673 8.5668109 2.3285285 0.0265426 -3.472333 FAM26F

family with sequence similarit

ILMN_176 0.3027297 0.3027297 8.0787221 2.2209172 0.0337565 -3.609015 TCN1

transcobalamin I (vitamin B12

ILMN_178 0.2995241 0.2995241 9.0349633 2.1002375 0.0438964 -3.757421 TNFAIP6

tumor necrosis factor, alpha-i

ILMN_168 0.2974007 0.2974007 9.4862321 2.3054219 0.0279622 -3.502012 TXN

thioredoxin

ILMN_238 0.2954768 0.2954768 8.5485505 2.5669289 0.0152809 -3.156386 DHRS9

dehydrogenase/reductase (SD

ILMN_170 0.2823915 0.2823915 9.9912609 2.6421445 0.0127707 -3.053318 AIF1

allograft inflammatory factor 1

ILMN_172 0.2773379 0.2773379 8.5763865 2.1448310 0.0398711 -3.703206 GK

glycerol kinase

ILMN_166 0.2753990 0.2753990 8.2662869 2.4572596 0.0197634 -3.303852 P2RY13

purinergic receptor P2Y, G-pr

ILMN_177 -0.275290 0.2752909 10.473565 -2.112893 0.0427189 -3.742111 FAIM3

Fas apoptotic inhibitory molec

ILMN_178 -0.264826 0.2648261 9.7425701 -2.244782 0.0320196 -3.579045 ABLIM1

actin binding LIM protein 1

ILMN_203 0.2621274 0.2621274 10.100370 2.0793865 0.0458990 -3.782512 TXN

thioredoxin

ILMN_176 0.2611775 0.2611775 10.346573 2.3577938 0.0248384 -3.434492 IL13RA1

interleukin 13 receptor, alpha

ILMN_166 -0.250017 0.2500175 9.5065276 -2.288155 0.0290675 -3.524073 IL11RA

interleukin 11 receptor, alpha

ILMN_324 -0.249884 0.2498840 9.6870791 -2.124133 0.0416966 -3.728461 LOC10019 uncharacterized LOC1001909 ILMN_233 -0.248354 0.2483541 9.6630781 -2.101249 0.0438012 -3.756199 CDC25B

cell division cycle 25B

ILMN_176 0.2476175 0.2476175 8.4240685 2.2852028 0.0292604 -3.527836 ABCA1

ATP-binding cassette, sub-fam

ILMN_168 0.2441411 0.2441411 8.2281878 2.1467184 0.0397082 -3.700895 TREM1

triggering receptor expressed

ILMN_170 0.2431104 0.2431104 9.0592103 2.3493559 0.0253193 -3.445431 LACTB

lactamase, beta

ILMN_169 0.2408099 0.2408099 9.8732253 2.1817611 0.0367897 -3.657750 CMTM6

CKLF-like MARVEL transmem

ILMN_323 0.2389209 0.2389209 8.0917202 2.9031788 0.0067305 -2.684869 SNORD89 small nucleolar RNA, C/D box ILMN_170 0.2362024 0.2362024 8.3196052 2.1199321 0.0420762 -3.733569 FBXO6

F-box protein 6

ILMN_175 -0.235310 0.2353101 9.7865589 -2.517273 0.0171797 -3.223583 SF3A2

splicing factor 3a, subunit 2, 6

ILMN_172 -0.232051 0.2320517 8.2046729 -2.350841 0.0252340 -3.443507 HMBOX1

homeobox containing 1

ILMN_171 -0.230800 0.2308003 8.6584273 -2.189086 0.0362044 -3.648675 PRAM1

PML-RARA regulated adapto

ILMN_324 -0.229077 0.2290776 11.476460 -2.271968 0.0301393 -3.544664 LOC61303 nuclear pore complex interact ILMN_321 0.2285152 0.2285152 8.5610846 2.0415127 0.0497437 -3.827659 NA

NA

ILMN_176 0.2284983 0.2284983 9.0924766 2.2349089 0.0327282 -3.591469 PSMB8

proteasome (prosome, macro

ILMN_241 -0.227423 0.2274233 9.0851065 -2.554813 0.0157254 -3.172845 CLSTN1

calsyntenin 1

ILMN_175 0.2221947 0.2221947 11.992750 2.0486142 0.0490019 -3.819236 SAT1

spermidine/spermine N1-acet

ILMN_168 -0.218605 0.2186059 8.4532470 -2.394613 0.0228357 -3.386492 PTDSS1

phosphatidylserine synthase 1

ILMN_176 -0.217093 0.2170935 10.271391 -2.230877 0.0330216 -3.596532 ESYT1

extended synaptotagmin-like

ILMN_181 0.2162558 0.2162558 10.979370 2.5444249 0.0161161 -3.186925 NOP10

NOP10 ribonucleoprotein

ILMN_176 -0.213927 0.2139273 10.837766 -2.302709 0.0281333 -3.505484 NA

NA

ILMN_179 0.2119237 0.2119237 8.9482967 2.1385428 0.0404181 -3.710896 SMCO4

single-pass membrane protei

ILMN_169 -0.211797 0.2117977 9.5064051 -2.253800 0.0313845 -3.567668 LOC61303 nuclear pore complex interact ILMN_232 0.2102289 0.2102289 9.7885606 2.0813699 0.0457051 -3.780133 CASP1

caspase 1, apoptosis-related

ILMN_180 0.2075162 0.2075162 9.2992781 2.7042978 0.0109911 -2.967042 ROMO1

reactive oxygen species modu

ILMN_237 -0.207441 0.2074419 10.724402 -2.229708 0.0331071 -3.597998 DDX17

DEAD (Asp-Glu-Ala-Asp) box

ILMN_210 0.2068662 0.2068662 8.9336481 2.4414397 0.0205013 -3.324834 ERICH1

glutamate-rich 1

ILMN_203 0.2052959 0.2052959 11.133916 2.1172340 0.0423215 -3.736845 RPS9

ribosomal protein S9

ILMN_166 0.2049531 0.2049531 8.4870849 2.5142771 0.0173010 -3.227615 IRAK3

interleukin-1 receptor-associa

ILMN_177 0.2040427 0.2040427 9.4853769 2.1969376 0.0355863 -3.638926 PGK1

phosphoglycerate kinase 1

ILMN_172 0.2038793 0.2038793 13.460701 2.6092945 0.0138159 -3.098518 B2M

beta-2-microglobulin

ILMN_167 -0.202242 0.2022421 8.8935353 -2.178142 0.0370819 -3.662226 NA

NA

ILMN_235 -0.201728 0.2017287 10.516836 -2.305399 0.0279637 -3.502041 RASSF2

Ras association (RalGDS/AF

ILMN_209 -0.200926 0.2009266 9.6114509 -2.201809 0.0352075 -3.632865 ZBTB4

zinc finger and BTB domain c

ILMN_232 -0.199836 0.1998367 9.5813846 -3.198226 0.0031679 -2.251951 CAST

calpastatin

ILMN_231 -0.199196 0.1991964 8.8793230 -2.136432 0.0406031 -3.713474 DGKA

diacylglycerol kinase, alpha 8

ILMN_168 -0.198679 0.1986793 10.332793 -2.337112 0.0260321 -3.461263 NA

NA

ILMN_176 0.1983771 0.1983771 10.264324 2.2230509 0.0335978 -3.606344 SUMO2

small ubiquitin-like modifier 2

ILMN_173 0.1983567 0.1983567 8.4791044 2.8452882 0.0077753 -2.767905 NBN

nibrin

ILMN_167 0.1972773 0.1972773 10.439409 2.2463391 0.0319092 -3.577084 CASP4

caspase 4, apoptosis-related

ILMN_171 0.1957236 0.1957236 8.2500109 2.5409996 0.0162468 -3.191561 TSNAX

translin-associated factor X

ILMN_173 -0.194470 0.1944708 10.205917 -2.459329 0.0196686 -3.301101 SRRM2

serine/arginine repetitive matr

ILMN_172 -0.191673 0.1916733 9.7255042 -2.200485 0.0353100 -3.634513 TTC3

tetratricopeptide repeat doma

ILMN_172 0.1915637 0.1915637 10.236086 2.1941722 0.0358029 -3.642362 LYSMD2

LysM, putative peptidoglycan

ILMN_230 -0.190992 0.1909928 8.0054549 -2.307149 0.0278538 -3.499799 CACNA1I calcium channel, voltage-dep ILMN_180 -0.190029 0.1900295 8.9372290 -2.303376 0.0280912 -3.504631 ACAP1

ArfGAP with coiled-coil, ankyr

ILMN_223 0.1890603 0.1890603 8.7374488 2.5732815 0.0150524 -3.147740 APOBEC3 apolipoprotein B mRNA editin ILMN_180 0.1889509 0.1889509 9.6968007 2.2400180 0.0323598 -3.585044 GSTO1

glutathione S-transferase ome

ILMN_174 0.1884655 0.1884655 11.562886 2.0473066 0.0491378 -3.820788 RPS9

ribosomal protein S9

ILMN_169 0.1881333 0.1881333 8.2043030 3.8789129 0.0005076 -1.213049 MAD2L1B MAD2L1 binding protein ILMN_167 -0.187734 0.1877349 8.9807929 -2.143244 0.0400084 -3.705147 CAST

calpastatin

ILMN_171 0.1861977 0.1861977 10.398229 2.3160949 0.0272982 -3.488325 ATP6V0E1 ATPase, H+ transporting, lyso ILMN_177 0.1857349 0.1857349 8.1893679 2.4269849 0.0211975 -3.343939 ZCCHC6

zinc finger, CCHC domain co

ILMN_169 0.1849660 0.1849660 9.6012107 2.1625152 0.0383680 -3.681501 CD300A

CD300a molecule

ILMN_241 -0.183549 0.1835494 9.8702329 -2.706446 0.0109339 -2.964042 ATP1A1

ATPase, Na+/K+ transporting

ILMN_170 -0.182795 0.1827953 8.8860864 -2.490945 0.0182724 -3.258927 PSTPIP1

proline-serine-threonine phos

ILMN_171 -0.181424 0.1814248 10.628732 -2.100160 0.0439036 -3.757514 AHNAK

AHNAK nucleoprotein

ILMN_232 0.1808547 0.1808547 12.341569 2.3273108 0.0266158 -3.473901 MYL6

myosin, light chain 6, alkali, s

ILMN_165 0.1795228 0.1795228 8.2804805 2.6310909 0.0131140 -3.068559 ACOT9

acyl-CoA thioesterase 9

ILMN_323 0.1789726 0.1789726 8.6683043 2.2463826 0.0319061 -3.577029 ROMO1

reactive oxygen species modu

ILMN_209 -0.178145 0.1781457 8.2896890 -2.102069 0.0437242 -3.755208 SPTAN1

spectrin, alpha, non-erythrocy

ILMN_169 -0.176733 0.1767339 8.2648138 -2.181700 0.0367946 -3.657825 NA

NA

ILMN_170 -0.176530 0.1765307 8.7095532 -2.186491 0.0364107 -3.651892 ITPKB

inositol-trisphosphate 3-kinas

ILMN_165 -0.175785 0.1757858 10.658166 -2.628166 0.0132062 -3.072586 PTBP1

polypyrimidine tract binding p

ILMN_167 0.1757435 0.1757435 8.9997850 2.1124820 0.0427567 -3.742609 RILPL2

Rab interacting lysosomal pro

ILMN_179 -0.174472 0.1744721 8.6642096 -2.053852 0.0484611 -3.813011 TBCD

tubulin folding cofactor D

ILMN_171 0.1744393 0.1744393 8.5144729 2.3044924 0.0280208 -3.503202 RABEP1

rabaptin, RAB GTPase bindin

ILMN_181 -0.173675 0.1736757 8.8495415 -2.380621 0.0235788 -3.404783 DCAKD

dephospho-CoA kinase doma

ILMN_171 0.1732452 0.1732452 9.7226474 2.1487315 0.0395351 -3.698429 TP53INP1 tumor protein p53 inducible n ILMN_172 -0.172412 0.1724122 8.2635281 -2.669217 0.0119650 -3.015857 PELP1

proline, glutamate and leucine

ILMN_171 0.1722610 0.1722610 9.3167504 3.0458094 0.0046925 -2.477470 ETFA

electron-transfer-flavoprotein,

ILMN_170 0.1708270 0.1708270 9.9255458 2.2161990 0.0341097 -3.614916 MRPL33

mitochondrial ribosomal prote

ILMN_167 -0.170201 0.1702016 8.6776991 -2.210854 0.0345138 -3.621592 MYO9B

myosin IXB

ILMN_173 0.1696674 0.1696674 9.8224184 2.1407008 0.0402296 -3.708259 SFT2D1

SFT2 domain containing 1

ILMN_224 -0.168866 0.1688665 10.056164 -2.188142 0.0362793 -3.649844 SON

SON DNA binding protein

ILMN_174 -0.168472 0.1684723 8.6060727 -2.103384 0.0436009 -3.753620 NRROS

negative regulator of reactive

ILMN_173 -0.168161 0.1681610 12.917589 -2.120074 0.0420633 -3.733396 KLF2

Kruppel-like factor 2

ILMN_239 0.1667480 0.1667480 9.3808640 2.4427714 0.0204382 -3.323071 SYF2

SYF2 pre-mRNA-splicing fact

ILMN_177 -0.166044 0.1660440 8.5955511 -2.587402 0.0145559 -3.128481 ZNF395

zinc finger protein 395

ILMN_216 -0.165594 0.1655941 8.3925749 -2.631657 0.0130962 -3.067779 NUMA1

nuclear mitotic apparatus pro

ILMN_237 -0.165072 0.1650721 9.8734101 -2.657293 0.0123139 -3.032380 RASGRP2 RAS guanyl releasing protein ILMN_167 -0.163956 0.1639563 9.6404957 -2.047813 0.0490851 -3.820187 TAF1C

TATA box binding protein (TB

ILMN_171 -0.163417 0.1634176 10.284275 -2.082077 0.0456361 -3.779283 TBC1D10C TBC1 domain family, membe ILMN_166 0.1625842 0.1625842 9.0796586 2.0584868 0.0479869 -3.807494 HTATIP2

HIV-1 Tat interactive protein 2

ILMN_166 -0.162264 0.1622645 9.3932739 -2.393017 0.0229193 -3.388581 AARS

alanyl-tRNA synthetase

ILMN_180 0.1618106 0.1618106 8.6867421 2.3019843 0.0281792 -3.506412 APOBEC3 apolipoprotein B mRNA editin

ILMN_178 0.1615623 0.1615623 8.7256605 2.3416572 0.0257654 -3.455391 SPCS2P4 signal peptidase complex sub ILMN_165 0.1604217 0.1604217 11.277976 2.3835590 0.0234209 -3.400948 NA

NA

ILMN_169 -0.158535 0.1585350 8.8012754 -2.141866 0.0401281 -3.706833 ILF3

interleukin enhancer binding f

ILMN_177 -0.158196 0.1581960 8.4822121 -2.314735 0.0273820 -3.490070 SMARCC2 SWI/SNF related, matrix asso ILMN_176 0.1564803 0.1564803 9.9112926 2.0955868 0.0443362 -3.763032 HLA-F

major histocompatibility comp

ILMN_175 -0.154675 0.1546750 8.3659575 -2.416138 0.0217341 -3.358233 SMARCB1 SWI/SNF related, matrix asso ILMN_176 0.1529077 0.1529077 9.0605531 2.1624294 0.0383751 -3.681607 NDUFB6

NADH dehydrogenase (ubiqu

ILMN_179 -0.152638 0.1526380 9.3539192 -2.481148 0.0186950 -3.272027 RASGRP2 RAS guanyl releasing protein ILMN_173 -0.152418 0.1524187 8.0405075 -2.171934 0.0375881 -3.669894 MED16

mediator complex subunit 16

ILMN_166 0.1519221 0.1519221 10.852210 3.1014151 0.0040694 -2.395625 COX5B

cytochrome c oxidase subunit

ILMN_169 -0.151715 0.1517159 8.5515721 -2.063633 0.0474651 -3.801357 PAQR8

progestin and adipoQ recepto

ILMN_172 -0.150076 0.1500763 9.2564503 -2.081189 0.0457227 -3.780349 CARD11

caspase recruitment domain f

ILMN_179 -0.149092 0.1490927 9.5096592 -2.177337 0.0371472 -3.663221 SMARCA2 SWI/SNF related, matrix asso ILMN_166 0.1490640 0.1490640 8.6422645 2.5045050 0.0177019 -3.240748 SUMO2

small ubiquitin-like modifier 2

ILMN_177 -0.148412 0.1484123 8.4326814 -2.281224 0.0295221 -3.532901 PRKCA

protein kinase C, alpha

ILMN_175 0.1483973 0.1483973 8.9992903 2.5532061 0.0157853 -3.175026 LOC10050 protein LLP homolog

ILMN_165 -0.147090 0.1470909 8.7239560 -2.269350 0.0303159 -3.547986 ZSCAN18 zinc finger and SCAN domain ILMN_214 0.1469044 0.1469044 8.9928417 2.5481232 0.0159760 -3.181916 NENF

neudesin neurotrophic factor

ILMN_180 0.1468222 0.1468222 8.5937797 2.1736734 0.0374457 -3.667747 NTAN1

N-terminal asparagine amidas

ILMN_175 0.1462187 0.1462187 8.8500276 2.8007201 0.0086816 -2.831343 TMEM60

transmembrane protein 60

ILMN_180 0.1458760 0.1458760 8.8741500 2.2491229 0.0317125 -3.573573 PARP8

poly (ADP-ribose) polymerase

ILMN_180 -0.142163 0.1421636 8.7307136 -2.576175 0.0149494 -3.143798 NFX1

nuclear transcription factor, X

ILMN_173 -0.141516 0.1415166 8.9233207 -2.355701 0.0249569 -3.437206 NISCH

nischarin

ILMN_176 -0.141265 0.1412659 8.1381786 -2.207277 0.0347867 -3.626054 GATAD2B GATA zinc finger domain con ILMN_166 -0.140736 0.1407368 8.9682227 -2.042232 0.0496682 -3.826806 TRRAP

transformation/transcription d

ILMN_175 -0.140635 0.1406358 10.051511 -2.052052 0.0486464 -3.815152 ST6GAL1 ST6 beta-galactosamide alph ILMN_232 -0.140550 0.1405508 9.5158208 -2.379651 0.0236311 -3.406049 DHPS

deoxyhypusine synthase

ILMN_205 -0.139783 0.1397836 8.3676003 -2.854793 0.0075939 -2.754319 UCKL1

uridine-cytidine kinase 1-like 1

ILMN_221 0.1391852 0.1391852 9.5163287 2.3052388 0.0279738 -3.502246 TMED10P transmembrane emp24-like tr ILMN_175 -0.137423 0.1374233 8.6256104 -2.224309 0.0335046 -3.604767 RPS6KA4 ribosomal protein S6 kinase, ILMN_236 0.1368886 0.1368886 8.3516536 2.0522942 0.0486214 -3.814864 NDUFB6

NADH dehydrogenase (ubiqu

ILMN_175 -0.133932 0.1339329 8.2662771 -2.198968 0.0354279 -3.636401 MAN2B1

mannosidase, alpha, class 2B

ILMN_176 -0.133907 0.1339075 8.2752458 -2.051695 0.0486832 -3.815576 WDR48

WD repeat domain 48

ILMN_323 0.1328702 0.1328702 9.4040606 2.5498117 0.0159124 -3.179628 SDHAF2

succinate dehydrogenase com

ILMN_166 -0.132735 0.1327350 8.0045881 -2.268556 0.0303697 -3.548994 PIP5K1C

phosphatidylinositol-4-phosph

ILMN_167 -0.132385 0.1323859 8.5525694 -2.124943 0.0416238 -3.727476 USP5

ubiquitin specific peptidase 5

ILMN_174 -0.131648 0.1316484 8.2781130 -2.317352 0.0272209 -3.486710 ABCA7

ATP-binding cassette, sub-fam

ILMN_323 -0.131616 0.1316167 9.1825581 -2.260998 0.0308857 -3.558568 MMS19

MMS19 nucleotide excision re

ILMN_175 -0.131196 0.1311969 8.5779671 -2.302253 0.0281622 -3.506068 NA

NA

ILMN_168 0.1309403 0.1309403 8.0262423 2.0924123 0.0446387 -3.766857 NA

NA

ILMN_168 -0.130440 0.1304402 9.0257339 -2.344017 0.0256279 -3.452339 IL27RA

interleukin 27 receptor, alpha

ILMN_220 -0.129880 0.1298808 9.6330711 -2.142663 0.0400589 -3.705858 KANSL1

KAT8 regulatory NSL comple

ILMN_212 -0.129665 0.1296654 9.0384761 -2.185198 0.0365140 -3.653494 FOXJ3

forkhead box J3

ILMN_174 -0.128367 0.1283679 9.0608711 -2.592687 0.0143740 -3.121259 GTF3C2

general transcription factor III

ILMN_212 -0.127953 0.1279530 9.4188200 -2.706775 0.0109252 -2.963583 MRPS18B mitochondrial ribosomal prote ILMN_222 -0.127905 0.1279056 9.8723935 -2.095814 0.0443146 -3.762757 MCM3

minichromosome maintenanc

ILMN_174 0.1261357 0.1261357 8.5132408 2.1412726 0.0401798 -3.707559 PWP1

PWP1 homolog (S. cerevisiae

ILMN_172 -0.125763 0.1257635 8.0597617 -2.539403 0.0163081 -3.193720 GTF2H1

general transcription factor IIH

ILMN_170 -0.124208 0.1242081 9.3241079 -2.174347 0.0373906 -3.666914 NCOA3

nuclear receptor coactivator 3

ILMN_170 -0.124153 0.1241530 8.1332668 -2.281611 0.0294966 -3.532409 SUPT5H

suppressor of Ty 5 homolog (

ILMN_166 -0.122653 0.1226532 8.0306221 -2.916589 0.0065080 -2.665535 GRHPR

glyoxylate reductase/hydroxyp

ILMN_179 -0.121080 0.1210801 9.2704902 -2.317861 0.0271896 -3.486055 KDM2B

lysine (K)-specific demethylas

ILMN_176 -0.120940 0.1209407 8.7455909 -2.249166 0.0317094 -3.573518 DGKD

diacylglycerol kinase, delta 13

ILMN_179 0.1202834 0.1202834 9.4290103 2.5011000 0.0178436 -3.245318 CCDC28A coiled-coil domain containing ILMN_174 -0.120061 0.1200613 8.8977670 -2.082944 0.0455516 -3.778242 KANSL3

KAT8 regulatory NSL comple

ILMN_328 -0.118229 0.1182297 8.0015874 -2.480832 0.0187088 -3.272449 NA

NA

ILMN_169 -0.117497 0.1174970 8.2432015 -2.387081 0.0232330 -3.396346 NCL

nucleolin

ILMN_170 0.1174629 0.1174629 9.0373143 2.3770589 0.0237714 -3.409430 EXOSC3

exosome component 3

ILMN_169 0.1173222 0.1173222 8.1543083 2.2633048 0.0307274 -3.555649 GNPAT

glyceronephosphate O-acyltra

ILMN_167 0.1164729 0.1164729 8.2518996 2.1922446 0.0359546 -3.644756 MRPL44

mitochondrial ribosomal prote

ILMN_173 -0.116056 0.1160560 9.0084512 -2.049254 0.0489355 -3.818475 C7orf26

chromosome 7 open reading

ILMN_165 -0.114814 0.1148147 11.145092 -2.057705 0.0480665 -3.808424 ALKBH5

alkB, alkylation repair homolo

ILMN_181 0.1137650 0.1137650 8.2149437 2.1471170 0.0396739 -3.700407 RAB7L1

RAB7, member RAS oncogen

ILMN_171 -0.113413 0.1134130 8.1821290 -2.292119 0.0288103 -3.519017 MRPL38

mitochondrial ribosomal prote

ILMN_175 0.1132934 0.1132934 9.2122136 2.1287513 0.0412831 -3.722841 SAP30L

SAP30-like

ILMN_173 0.1129078 0.1129078 8.3827320 2.1668223 0.0380096 -3.676198 YME1L1

YME1-like 1 ATPase

ILMN_324 -0.109518 0.1095188 9.0193716 -2.183834 0.0366232 -3.655183 DCAF8

DDB1 and CUL4 associated f

ILMN_179 -0.109496 0.1094965 8.1083778 -2.165537 0.0381162 -3.677781 PPRC1

peroxisome proliferator-activa

ILMN_179 -0.109433 0.1094336 8.6428115 -2.530703 0.0166458 -3.205476 POLR3C

polymerase (RNA) III (DNA d

ILMN_166 -0.109272 0.1092727 8.4696192 -2.282902 0.0294115 -3.530766 TMUB1

transmembrane and ubiquitin

ILMN_229 -0.109160 0.1091601 8.2077210 -2.485161 0.0185208 -3.266664 TMEM150 transmembrane protein 150A ILMN_171 -0.106259 0.1062598 8.2343498 -2.696074 0.0112125 -2.978512 TRIM11

tripartite motif containing 11

ILMN_179 -0.105962 0.1059626 8.6395796 -2.340346 0.0258421 -3.457085 MARS

methionyl-tRNA synthetase

ILMN_228 -0.105290 0.1052908 8.2259702 -2.089283 0.0449386 -3.770623 TRAK1

trafficking protein, kinesin bin

ILMN_323 0.1035721 0.1035721 8.3718377 2.0466162 0.0492097 -3.821608 SNHG9

small nucleolar RNA host gen

ILMN_179 0.1033054 0.1033054 8.2444115 2.1278804 0.0413608 -3.723902 ATPAF1

ATP synthase mitochondrial F

ILMN_176 -0.103290 0.1032906 8.3787651 -2.313476 0.0274597 -3.491686 PHF13

PHD finger protein 13

ILMN_167 -0.103087 0.1030876 8.1209458 -2.101596 0.0437686 -3.755780 NA

NA

ILMN_169 0.1028802 0.1028802 9.3758626 2.1062001 0.0433381 -3.750215 CETN2

centrin, EF-hand protein, 2

ILMN_169 -0.102751 0.1027515 8.0255903 -2.364934 0.0244380 -3.425217 DPAGT1

dolichyl-phosphate (UDP-N-a

ILMN_177 0.1026005 0.1026005 8.4653602 2.0783310 0.0460025 -3.783778 SNRPB2

small nuclear ribonucleoprote

ILMN_324 -0.102571 0.1025716 8.6969839 -2.125830 0.0415443 -3.726398 CCDC93

coiled-coil domain containing

ILMN_324 -0.101392 0.1013924 8.4460070 -2.189886 0.0361409 -3.647682 NA

NA

ILMN_236 0.1008676 0.1008676 8.7145296 2.0654956 0.0472776 -3.799135 PPP2R5C protein phosphatase 2, regula ILMN_235 -0.100112 0.1001120 8.1253463 -2.251496 0.0315457 -3.570578 GTF3C2

general transcription factor III

ILMN_235 -0.099464 0.0994640 9.0338463 -2.255283 0.0312811 -3.565795 EIF2B4

eukaryotic translation initiation

ILMN_176 -0.099223 0.0992238 9.7366352 -2.069769 0.0468496 -3.794029 RDH11

retinol dehydrogenase 11 (all

ILMN_172 -0.099110 0.0991102 8.8346201 -2.068130 0.0470133 -3.795988 RSU1

Ras suppressor protein 1

ILMN_174 0.0969039 0.0969039 8.3642680 2.1648227 0.0381756 -3.678661 WTAP

Wilms tumor 1 associated pro

ILMN_166 0.0956495 0.0956495 9.0401994 2.0801125 0.0458279 -3.781641 HSBP1

heat shock factor binding prot

ILMN_176 0.0949733 0.0949733 8.2561739 2.1459764 0.0397722 -3.701804 TTL

tubulin tyrosine ligase

ILMN_172 0.0943032 0.0943032 8.3737957 2.2140902 0.0342686 -3.617551 SCO1

SCO1 cytochrome c oxidase

ILMN_166 0.0916935 0.0916935 9.9668055 2.0870100 0.0451576 -3.773358 SDHB

succinate dehydrogenase com

ILMN_172 0.0911344 0.0911344 9.5863885 2.0775373 0.0460805 -3.784729 TAF10

TAF10 RNA polymerase II, TA

ILMN_172 0.0907423 0.0907423 8.5748923 2.0651856 0.0473087 -3.799505 NA

NA

ILMN_176 -0.089618 0.0896182 8.0312825 -2.220426 0.0337931 -3.609629 SELO

selenoprotein O

ILMN_221 -0.087716 0.0877164 8.1370788 -2.113295 0.0426819 -3.741623 RFC1

replication factor C (activator

ILMN_167 -0.075065 0.0750651 8.1297198 -2.251524 0.0315437 -3.570543 MTA1

metastasis associated 1

Probe

logFC

abs(logFC) AveExpr

t

P.Value

B

symbol

name

ILMN_177 0.2002942 0.2002942 9.7392905 2.1982211 0.0314783 -3.531097 IL1R2

interleukin 1 receptor, type II

ILMN_180 -0.197193 0.1971934 8.4053347 -2.511301 0.0145079 -2.963831 NA

NA

ILMN_223 0.1858090 0.1858090 12.598440 2.4126624 0.0186491 -3.149163 KCNH6

potassium voltage-gated chan

ILMN_174 0.1767062 0.1767062 9.0577826 2.6339678 0.0105233 -2.725197 HCG27

HLA complex group 27 (non-p

ILMN_176 0.1719647 0.1719647 8.1438202 2.1073044 0.0389303 -3.684054 CD8A

CD8a molecule

ILMN_238 0.1698721 0.1698721 8.1430262 2.7151781 0.0084632 -2.562374 FAM212B family with sequence similarit ILMN_324 0.1604908 0.1604908 12.631082 2.2408335 0.0284388 -3.457542 NA

NA

ILMN_213 0.1588577 0.1588577 12.809962 2.0109694 0.0484546 -3.840110 CDKN2AI CDKN2A interacting protein N ILMN_238 0.1518526 0.1518526 12.325216 2.0211647 0.0473598 -3.823891 CRCP

CGRP receptor component

ILMN_324 0.1464084 0.1464084 8.5268131 2.4728550 0.0160118 -3.036774 NA

NA

ILMN_190 -0.125624 0.1256243 8.2808242 -2.178858 0.0329512 -3.564129 LINC00339 long intergenic non-protein co

ILMN_165 0.1211710 0.1211710 9.5650882 2.2683904 0.0266137 -3.409350 PPP1R15 protein phosphatase 1, regula ILMN_229 0.1205315 0.1205315 8.2694864 2.1875294 0.0322843 -3.549367 RAB3IP

RAB3A interacting protein

ILMN_235 -0.118712 0.1187121 8.0061245 -2.428729 0.0179096 -3.119381 BEX4

brain expressed, X-linked 4

ILMN_174 -0.115597 0.1155975 8.3775313 -2.954823 0.0043453 -2.060399 TCEAL4

transcription elongation factor

ILMN_237 -0.114864 0.1148643 8.8007419 -2.507558 0.0146485 -2.970972 AKTIP

AKT interacting protein

ILMN_212 -0.113617 0.1136175 8.2481489 -2.043390 0.0450467 -3.788290 NA

NA

ILMN_330 0.1114765 0.1114765 8.0947049 2.2568541 0.0273648 -3.429584 MIR223

microRNA 223

ILMN_181 0.1090921 0.1090921 9.3193037 2.6601658 0.0098136 -2.673086 HMHA1

histocompatibility (minor) HA-

ILMN_181 -0.108469 0.1084696 8.0454972 -2.283595 0.0256517 -3.382550 CTSL

cathepsin L

ILMN_174 0.1075379 0.1075379 8.6734341 2.1096133 0.0387235 -3.680238 CD33

CD33 molecule

ILMN_181 0.1065848 0.1065848 8.6147603 2.9034430 0.0050277 -2.170654 EIF5

eukaryotic translation initiation

ILMN_177 0.1061355 0.1061355 8.9450698 2.1864649 0.0323656 -3.551182 MPPE1

metallophosphoesterase 1

ILMN_179 0.1036668 0.1036668 8.3090217 2.3943782 0.0195239 -3.182860 NA

NA

ILMN_166 -0.103115 0.1031156 8.3169563 -3.161256 0.0023810 -1.603645 ACAA2

acetyl-CoA acyltransferase 2

ILMN_180 0.1011996 0.1011996 9.1337692 2.1612647 0.0343416 -3.593930 SPEN

spen family transcriptional rep

ILMN_172 -0.097801 0.0978013 8.0415610 -2.180326 0.0328375 -3.561633 POLR2I

polymerase (RNA) II (DNA dir

ILMN_186 0.0971571 0.0971571 8.0234367 2.6689479 0.0095856 -2.655528 NA

NA

ILMN_173 -0.096958 0.0969585 9.1814775 -2.131751 0.0367891 -3.643462 NA

NA

ILMN_180 0.0958942 0.0958942 11.243127 2.0064021 0.0489520 -3.847353 MCL1

myeloid cell leukemia 1

ILMN_184 0.0949486 0.0949486 8.1848270 3.5873375 0.0006387 -0.596464 SAP30L

SAP30-like

ILMN_176 0.0947065 0.0947065 8.0514517 2.0765986 0.0417724 -3.734474 SNX29

sorting nexin 29

ILMN_165 -0.090924 0.0909245 8.0606149 -2.649213 0.0101048 -2.694920 METTL22 methyltransferase like 22 ILMN_181 0.0895713 0.0895713 9.9709725 2.5486956 0.0131686 -2.892031 RHOQ

ras homolog family member Q

ILMN_170 -0.088934 0.0889341 8.4234171 -2.435003 0.0176280 -3.107707 PLGRKT

plasminogen receptor, C-term

ILMN_175 -0.088190 0.0881902 8.2516017 -2.327718 0.0230318 -3.303944 TXNL1

thioredoxin-like 1

ILMN_330 0.0852343 0.0852343 13.371422 2.1246151 0.0374033 -3.655352 NA

NA

ILMN_190 0.0847848 0.0847848 8.1353033 2.4236541 0.0181403 -3.128806 NA

NA

ILMN_170 0.0842690 0.0842690 8.6317395 2.1497816 0.0352764 -3.613270 BANP

BTG3 associated nuclear pro

ILMN_214 0.0838707 0.0838707 8.0159594 2.0116861 0.0483769 -3.838972 TMCC1-A TMCC1 antisense RNA 1 (he ILMN_322 0.0838344 0.0838344 8.1441760 2.6554241 0.0099387 -2.682547 PRKCB

protein kinase C, beta

ILMN_169 -0.083688 0.0836884 10.098030 -2.235615 0.0287966 -3.466613 POMP

proteasome maturation protei

ILMN_215 -0.083304 0.0833041 8.5881396 -2.362285 0.0211484 -3.241502 FAM103A family with sequence similarit ILMN_173 -0.079705 0.0797059 8.0721319 -3.068537 0.0031292 -1.811475 POLR2C

polymerase (RNA) II (DNA dir

ILMN_169 0.0780628 0.0780628 9.3796592 2.0169599 0.0478087 -3.830589 SIVA1

SIVA1, apoptosis-inducing fac

ILMN_172 -0.077433 0.0774333 9.4568858 -2.060219 0.0433607 -3.761111 SETD3

SET domain containing 3

ILMN_176 -0.076124 0.0761249 9.7080299 -2.014139 0.0481119 -3.835075 RDH11

retinol dehydrogenase 11 (all-

ILMN_166 -0.074603 0.0746038 8.0307866 -2.177040 0.0330926 -3.567218 AKTIP

AKT interacting protein

ILMN_166 0.0716351 0.0716351 9.7607337 2.0733632 0.0420821 -3.739750 TNK2

tyrosine kinase, non-receptor,

ILMN_177 -0.071096 0.0710968 8.2850615 -2.120571 0.0377552 -3.662074 TUBGCP2 tubulin, gamma complex asso ILMN_204 0.0706306 0.0706306 13.400866 2.0097629 0.0485856 -3.842025 NA

NA

ILMN_168 0.0700788 0.0700788 8.4883759 2.0073534 0.0488481 -3.845845 ZNF274

zinc finger protein 274

ILMN_169 0.0697663 0.0697663 9.4361259 2.0769787 0.0417362 -3.733854 PLEKHO1 pleckstrin homology domain c ILMN_325 0.0690541 0.0690541 8.1093721 2.0587949 0.0435013 -3.763418 RER1

retention in endoplasmic retic

ILMN_238 -0.068818 0.0688186 8.2984711 -2.144630 0.0357030 -3.621918 RABL2B

RAB, member of RAS oncoge

ILMN_321 -0.067713 0.0677135 8.0202673 -2.265345 0.0268102 -3.414699 NA

NA

ILMN_235 -0.067193 0.0671936 8.0565863 -2.131761 0.0367882 -3.643445 RNF121

ring finger protein 121

ILMN_319 0.0659575 0.0659575 8.3903751 2.0348180 0.0459270 -3.802061 CBX1

chromobox homolog 1

ILMN_208 -0.065554 0.0655545 8.9558284 -2.145224 0.0356536 -3.620922 CPSF3

cleavage and polyadenylation

ILMN_233 -0.063898 0.0638988 9.0619905 -2.124155 0.0374431 -3.656116 TRAPPC1 trafficking protein particle com ILMN_235 0.0630258 0.0630258 8.0171614 2.2155597 0.0302088 -3.501311 OGG1

8-oxoguanine DNA glycosylas

ILMN_172 -0.060224 0.0602246 9.3105616 -2.169985 0.0336461 -3.579183 NIPA2

non imprinted in Prader-Willi/A

ILMN_221 -0.059780 0.0597802 9.3073340 -2.057634 0.0436160 -3.765297 CDC26

cell division cycle 26

ILMN_169 0.0594472 0.0594472 8.0463707 2.7423137 0.0078618 -2.507129 ATP2A3

ATPase, Ca++ transporting, u

ILMN_167 0.0559873 0.0559873 8.0269092 2.1189756 0.0378949 -3.664725 RNPS1

RNA binding protein S1, serin

ILMN_167 -0.055306 0.0553067 8.2953816 -2.077467 0.0416896 -3.733056 SLC37A4 solute carrier family 37 (gluco ILMN_220 -0.052735 0.0527358 11.752498 -2.219495 0.0299269 -3.494522 JTB

jumping translocation breakpo

ILMN_174 -0.051345 0.0513451 8.0016161 -2.027581 0.0466817 -3.813647 TMEM50A transmembrane protein 50A ILMN_174 -0.049082 0.0490820 8.1009899 -2.234205 0.0288939 -3.469061 AKAP8

A kinase (PRKA) anchor prote

ID logFC ILMN_323 -0.723705 ILMN_239 -0.563069 ILMN_173 -0.543027 ILMN_210 -0.455968 ILMN_210 -0.365718 ILMN_235 -0.358375 ILMN_176 -0.353086 ILMN_324 -0.343851 ILMN_176 -0.333801 ILMN_231 -0.332441 ILMN_179 -0.324347 ILMN_165 -0.312906 ILMN_179 -0.310814 ILMN_172 -0.299673 ILMN_238 -0.287062 ILMN_174 -0.277881 ILMN_177 -0.275855 ILMN_237 -0.270016 ILMN_177 -0.240585 ILMN_222 -0.239964 ILMN_178 -0.233502 ILMN_179 -0.230037 ILMN_165 -0.228678 ILMN_171 -0.227430 ILMN_207 -0.225035 ILMN_209 -0.224098 ILMN_176 -0.223635 ILMN_178 -0.212967 ILMN_236 -0.211915 ILMN_169 -0.211758 ILMN_233 -0.209300 ILMN_176 -0.208378 ILMN_179 -0.207988 ILMN_320 -0.204205 ILMN_170 -0.200982 ILMN_208 -0.200018 ILMN_180 -0.198189 ILMN_232 -0.197033 ILMN_323 -0.188363 ILMN_166 -0.184859 ILMN_167 -0.180229 ILMN_166 -0.172046 ILMN_178 -0.168689 ILMN_209 -0.167658

AveExpr t 8.9574757 -2.190838 10.934557 -2.639031 10.580731 -2.413376 8.1715554 -2.778824 10.535292 -2.288832 10.265416 -2.072927 10.250154 -2.069276 8.6433296 -2.241811 9.5928262 -2.329397 9.1615642 -2.397442 9.1301024 -2.775782 9.0202299 -3.074867 9.1678857 -2.572328 8.3152158 -3.271754 9.7698404 -2.087180 10.119534 -2.241219 10.768349 -2.692468 11.047153 -2.660257 9.1763562 -2.830181 9.5936023 -2.335284 10.968496 -2.731805 9.2405495 -3.381167 11.434765 -2.248139 10.726927 -2.934642 9.0410138 -2.030018 12.712296 -2.260975 8.0635660 -2.512997 9.2518185 -2.051224 10.405698 -2.806500 11.100708 -2.101069 9.6087514 -2.232216 10.257693 -2.203560 9.0271138 -2.101383 10.583250 -2.080030 11.805121 -2.141531 10.170104 -2.160224 10.664251 -2.359522 9.5730739 -2.365858 9.5277050 -2.067742 10.483944 -3.296424 8.5985835 -2.337757 8.8201301 -2.252638 8.3893125 -2.303941 9.9445923 -2.364318

P.Value adj.P.Val B name symbol 0.0341526 0.0498850 -3.568841 ribosomal RPS4Y1 0.0116701 0.0498850 -2.866551 immunogl IGLL1 0.0203176 0.0498850 -3.231305 granzyme GZMH 0.0081692 0.0498850 -2.630281 immunogl IGJ 0.0272656 0.0498850 -3.423071 granzyme GZMB 0.0444482 0.0498850 -3.737966 CD8a mol CD8A 0.0448063 0.0498850 -3.743089 CD8a mol CD8A 0.0303983 0.0498850 -3.493593 immunogl IGKV1ORY-1 0.0247985 0.0498850 -3.361394 fibroblast FGFBP2 0.0211070 0.0498850 -3.256233 HOP hom HOPX 0.0082337 0.0498850 -2.635501 killer cell KLRD1 0.0037225 0.0498850 -2.106873 killer cell KLRG1 0.0137870 0.0498850 -2.976588 killer cell KLRD1 0.0021609 0.0498850 -1.743550 TCR gam TARP 0.0430740 0.0498850 -3.717896 G protein- GPR56 0.0304397 0.0498850 -3.494475 perforin 1 PRF1 0.0101945 0.0498850 -2.777121 chemokin CCL5 0.0110619 0.0498850 -2.831163 TSC22 do TSC22D3 0.0071488 0.0498850 -2.541642 oligosacc OSTC 0.0244576 0.0498850 -3.352380 Ly1 antibo LYAR 0.0092204 0.0498850 -2.710580 runt-relat RUNX3 0.0015866 0.0498850 -1.537070 inhibitor ID2 0.0299588 0.0498850 -3.484164 cysteine-r CRIP1 0.0054286 0.0498850 -2.358472 AHNAK n AHNAK 0.0488195 0.0498850 -3.797751 sphingosi S1PR5 0.0290847 0.0498850 -3.464978 chemokin CCL5 0.0159594 0.0498850 -3.072927 CD8a mol CD8A 0.0466145 0.0498850 -3.768324 transform TGFBR3 0.0076036 0.0498850 -2.582633 X-box bin XBP1 0.0417707 0.0498850 -3.698239 ribosomal RPL18 0.0310756 0.0498850 -3.507854 small ubi SUMO2 0.0331790 0.0498850 -3.550179 small ubi SUMO2 0.0417416 0.0498850 -3.697793 eukaryoti EIF5A 0.0437586 0.0498850 -3.727977 ribosomal RPL23A 0.0381693 0.0498850 -3.640415 ribosomal RPS5 0.0365999 0.0498850 -3.613422 inhibitor ID2 0.0230980 0.0498850 -3.315098 X-box bin XBP1 0.0227540 0.0498850 -3.305307 GTPase, I GIMAP6 0.0449576 0.0498850 -3.745241 RELT-like RELL1 0.0020163 0.0498850 -1.697263 signal pep SPCS1 0.0243157 0.0498850 -3.348589 ATP synth ATP5F1 0.0296498 0.0498850 -3.477448 N-acyleth NAAA 0.0263222 0.0498850 -3.400189 retinoblas RBBP4 0.0228372 0.0498850 -3.307689 heat shoc HSP90B1

ILMN_323 -0.167556 ILMN_330 -0.165782 ILMN_175 -0.164922 ILMN_178 -0.163725 ILMN_239 -0.161413 ILMN_179 -0.161300 ILMN_178 -0.161298 ILMN_223 -0.158506 ILMN_178 -0.157869 ILMN_175 -0.155597 ILMN_228 -0.155508 ILMN_324 -0.145587 ILMN_212 -0.144358 ILMN_178 -0.142660 ILMN_166 -0.141351 ILMN_169 -0.140790 ILMN_215 -0.138747 ILMN_173 -0.138082 ILMN_165 -0.137750 ILMN_167 -0.137473 ILMN_167 -0.136091 ILMN_179 -0.135278 ILMN_175 -0.134992 ILMN_176 -0.132893 ILMN_221 -0.132882 ILMN_209 -0.132793 ILMN_181 -0.131425 ILMN_176 -0.129579 ILMN_213 -0.128515 ILMN_167 -0.128308 ILMN_166 -0.126783 ILMN_183 -0.126262 ILMN_173 -0.124557 ILMN_170 -0.124495 ILMN_218 -0.122821 ILMN_178 -0.122439 ILMN_165 -0.120779 ILMN_324 -0.120590 ILMN_176 -0.120397 ILMN_238 -0.119979 ILMN_168 -0.117382 ILMN_177 -0.115665 ILMN_166 -0.114350 ILMN_230 -0.114303 ILMN_176 -0.114188

9.9329859 -2.490033 8.2304960 -2.383609 8.5445673 -2.791665 8.9689617 -2.775727 8.6156958 -2.174414 11.954244 -2.295662 9.4267370 -2.559796 8.7625266 -2.241169 8.7631562 -3.208307 9.2181221 -2.113713 8.5068096 -2.175594 8.8372386 -2.619688 9.5423111 -2.109904 8.3587014 -2.163541 10.676508 -2.271620 9.0842133 -2.971458 10.504272 -2.360003 10.511220 -2.752114 9.1982181 -2.454894 10.987726 -2.045985 8.0457325 -2.126671 9.7396393 -2.227760 10.083318 -2.665836 9.8959874 -2.311869 9.5475196 -2.440636 10.104766 -2.058889 8.2391593 -2.314671 8.0542715 -2.174539 9.0966521 -2.141496 8.9136899 -2.939965 8.2973453 -2.389523 8.1028035 -2.169845 9.4118173 -2.503535 10.244919 -2.028891 9.1915055 -2.352345 9.6465543 -2.586095 9.5047524 -2.107813 8.4408216 -2.315027 8.1161050 -2.811029 9.2659782 -2.067200 8.1553231 -2.454277 9.2985023 -2.027269 8.2618579 -2.365245 9.6279502 -2.136073 8.7726413 -2.169701

0.0168809 0.0498850 -3.109816 heteroge HNRNPA1P33 0.0218146 0.0498850 -3.277781 protein as PATL2 0.0079021 0.0498850 -2.608207 Kruppel-li KLF11 0.0082349 0.0498850 -2.635595 FK506 bin FKBP11 0.0354469 0.0498850 -3.592816 N-acyleth NAAA 0.0268354 0.0498850 -3.412740 S100 calci S100A10 0.0142220 0.0498850 -2.997060 signal seq SSR2 0.0304432 0.0498850 -3.494550 apolipopr APOBEC3G 0.0025793 0.0498850 -1.861836 signal pep SPCS2P4 0.0406145 0.0498850 -3.680258 microsom MGST3 0.0353525 0.0498850 -3.591097 N-acyleth NAAA 0.0122510 0.0498850 -2.898645 transmem TMEM14B 0.0409598 0.0498850 -3.685684 heteroge HNRNPA1P33 0.0363275 0.0498850 -3.608614 neurocalc NCALD 0.0283772 0.0498850 -3.449008 transform TGFBI 0.0049208 0.0498850 -2.293030 EF-hand c EFCAB14 0.0230717 0.0498850 -3.314355 high mobi HMGN1 0.0087519 0.0498850 -2.675997 defender DAD1 0.0183848 0.0498850 -3.165824 transmem TMED2 0.0471510 0.0498850 -3.775616 tyrosine 3 YWHAQ 0.0394589 0.0498850 -3.661747 cell divisi CDC42 0.0313947 0.0498850 -3.514461 ezrin EZR 0.0109070 0.0498850 -2.821832 proteaso PSMA5 0.0258389 0.0498850 -3.388139 major hist HLA-F 0.0190289 0.0498850 -3.188397 transmem TMED10P1 0.0458391 0.0498850 -3.757630 placenta- PLAC8 0.0256700 0.0498850 -3.383873 RAB29, m RAB29 0.0354369 0.0498850 -3.592634 sorting ne SNX29 0.0381723 0.0498850 -3.640464 perilipin 2 PLIN2 0.0053523 0.0498850 -2.349037 aminoacyl AIMP2 0.0215095 0.0498850 -3.268580 G protein- GPR114 0.0358146 0.0498850 -3.599462 leucine ri LRRC8B 0.0163334 0.0498850 -3.088153 serine/thr STRAP 0.0489392 0.0498850 -3.799308 triosepho TPI1 0.0234933 0.0498850 -3.326165 mesence MANF 0.0133233 0.0498850 -2.954026 chromoso C19orf43 0.0411504 0.0498850 -3.688658 ZMYM6 n ZMYM6NB 0.0256486 0.0498850 -3.383331 succinate SDHC 0.0075146 0.0498850 -2.574809 ADP-ribos ARL4C 0.0450111 0.0498850 -3.746000 eukaryoti EIF6 0.0184122 0.0498850 -3.166803 mitochon MRPS15 0.0491119 0.0498850 -3.801548 copine III CPNE3 0.0227870 0.0498850 -3.306255 mortality MORF4L2 0.0386385 0.0498850 -3.648263 dynein, li DYNLL1 0.0358262 0.0498850 -3.599670 axin 1 AXIN1

ILMN_237 -0.113733 ILMN_176 -0.112362 ILMN_173 -0.111567 ILMN_168 -0.110700 ILMN_172 -0.110140 ILMN_320 -0.109697 ILMN_171 -0.109371 ILMN_175 -0.108007 ILMN_231 -0.107072 ILMN_233 -0.106995 ILMN_168 -0.106369 ILMN_172 -0.106249 ILMN_171 -0.103736 ILMN_215 -0.103078 ILMN_238 -0.103042 ILMN_169 -0.102719 ILMN_170 -0.101947 ILMN_173 -0.101939 ILMN_180 -0.100728 ILMN_166 -0.099802 ILMN_225 -0.099516 ILMN_175 -0.099335 ILMN_176 -0.097850 ILMN_205 -0.097218 ILMN_175 -0.096623 ILMN_166 -0.095688 ILMN_205 -0.094153 ILMN_170 -0.093018 ILMN_174 -0.092204 ILMN_180 -0.091705 ILMN_169 -0.091098 ILMN_166 -0.089714 ILMN_167 -0.089474 ILMN_172 -0.089174 ILMN_169 -0.087276 ILMN_235 -0.087172 ILMN_166 -0.086242 ILMN_167 -0.084942 ILMN_221 -0.083238 ILMN_170 -0.082791 ILMN_167 -0.082754 ILMN_173 -0.082492 ILMN_175 -0.082476 ILMN_212 -0.082332 ILMN_175 -0.080271

8.5525412 -2.538862 8.1636068 -2.038459 8.8083294 -2.668669 10.978026 -2.149295 8.2126172 -2.252211 9.1609522 -2.095941 9.3464229 -2.360275 9.2911358 -2.282837 9.2224782 -2.289483 10.673307 -2.466541 8.5501521 -2.281922 9.4986275 -2.546550 8.1736225 -2.105994 11.041822 -2.190516 8.6279232 -2.048421 9.3644624 -2.072869 8.4180196 -2.612264 8.5291231 -2.311118 10.131077 -2.728332 8.9644420 -2.091452 8.7859789 -2.051227 8.3339378 -2.239847 8.6672749 -2.301742 9.1799644 -2.394088 9.1076382 -2.511022 8.1008151 -2.138389 10.929240 -2.063900 8.1350385 -2.237255 8.1044019 -2.133093 10.709821 -2.187992 8.8362579 -2.520185 8.7051592 -2.308439 11.307301 -2.189085 9.9188684 -2.207753 13.462545 -2.117952 8.0227519 -2.380136 8.0535905 -2.584027 8.0075660 -2.810978 13.804465 -2.409682 8.1202581 -2.233339 8.3790689 -2.246379 10.318389 -2.181543 8.5255827 -2.375260 8.5643268 -2.088543 8.6287429 -2.081317

0.0149766 0.0498850 -3.031109 butyrophi BTN3A3 0.0479312 0.0498850 -3.786066 G protein- GIT2 0.0108291 0.0498850 -2.817089 phosphat PHACTR4 0.0375104 0.0498850 -3.629224 high mobi HMGN2 0.0296790 0.0498850 -3.478086 GTPase ac G3BP2 0.0422478 0.0498850 -3.705508 chaperoni CCT6P3 0.0230568 0.0498850 -3.313934 electron-t ETFA 0.0276483 0.0498850 -3.432120 DnaJ (Hsp DNAJB11 0.0272243 0.0498850 -3.422087 TROVE do TROVE2 0.0178733 0.0498850 -3.147319 solute car SLC25A3 0.0277071 0.0498850 -3.433501 Cbl proto- CBLB 0.0146953 0.0498850 -3.018625 regulator RCC2 0.0413169 0.0498850 -3.691245 Niemann- NPC1 0.0341776 0.0498850 -3.569313 cytochro COX6B1 0.0469008 0.0498850 -3.772227 DEAD (As DDX19B 0.0444539 0.0498850 -3.738047 SIVA1, ap SIVA1 0.0124809 0.0498850 -2.910924 oligosacc OSTCP2 0.0258843 0.0498850 -3.389282 coiled-coi CCDC92 0.0093028 0.0498850 -2.716480 signal pep SPCS2 0.0426694 0.0498850 -3.711861 Cbp/p300 CITED2 0.0466142 0.0498850 -3.768320 mitochon MRPL43 0.0305359 0.0498850 -3.496516 zinc finge ZNF791 0.0264576 0.0498850 -3.403526 TCDD-ind TIPARP 0.0212766 0.0498850 -3.261465 CD99 mol CD99 0.0160368 0.0498850 -3.076108 COP9 sign COPS7A 0.0384388 0.0498850 -3.644934 cytochro CYCS 0.0453383 0.0498850 -3.750623 non-POU NONO 0.0307183 0.0498850 -3.500370 sorting ne SNX5 0.0388969 0.0498850 -3.652541 coiled-coi CCSER2 0.0343739 0.0498850 -3.573005 Sec61 bet SEC61B 0.0156806 0.0498850 -3.061334 PR domai PRDM4 0.0260470 0.0498850 -3.393356 adaptor-r AP3M1 0.0342888 0.0498850 -3.571407 activating ATF4 0.0328635 0.0498850 -3.544011 esterase ESD 0.0402333 0.0498850 -3.674213 A kinase ( AKAP5 0.0219956 0.0498850 -3.283178 8-oxogua OGG1 0.0133920 0.0498850 -2.957419 translocas TIMM23 0.0075156 0.0498850 -2.574896 RNA bindi RNPS1 0.0204982 0.0498850 -3.237095 origin rec ORC6 0.0309956 0.0498850 -3.506187 FYVE and FYCO1 0.0300805 0.0498850 -3.486788 PDS5, reg PDS5A 0.0348799 0.0498850 -3.582425 dolichyl-d DDOST 0.0222520 0.0498850 -3.290745 cAMP res CREB3L2 0.0429445 0.0498850 -3.715972 RNA bindi RBMX 0.0436347 0.0498850 -3.726165 late endo LAMTOR2

ILMN_171 -0.080089 8.2599891 -2.151487 0.0373262 0.0498850 -3.626060 eukaryoti EIF2B2 ILMN_173 -0.079317 8.4703910 -2.373298 0.0223559 0.0498850 -3.293787 R3H doma R3HCC1 ILMN_171 -0.078420 8.9102849 -2.431640 0.0194458 0.0498850 -3.202593 UBA dom UBAC2 ILMN_165 -0.078047 8.0998782 -2.108040 0.0411297 0.0498850 -3.688336 glutamic- GOT1 ILMN_317 -0.077997 9.5286295 -2.061575 0.0455700 0.0498850 -3.753875 regulator RCC2 ILMN_326 -0.077097 8.2631575 -2.096627 0.0421837 0.0498850 -3.704537 chromoso C19orf60 ILMN_171 -0.074225 8.1334168 -2.157600 0.0368167 0.0498850 -3.617221 glycosyltr GLT8D1 ILMN_323 -0.070050 8.7018195 -2.244142 0.0302357 0.0498850 -3.490121 chromoso C1orf174 ILMN_179 -0.069519 8.2208529 -2.117670 0.0402585 0.0498850 -3.674614 small nucl SNRNP40 ILMN_177 -0.067547 9.1208101 -2.289343 0.0272332 0.0498850 -3.422299 proteaso PSMD7 ILMN_165 -0.066943 8.2029463 -2.330275 0.0247474 0.0498850 -3.360052 developm DRG1 ILMN_167 -0.063264 8.3013754 -2.074113 0.0443324 0.0498850 -3.736299 NADH de NDUFA7 ILMN_204 0.0629821 8.1278571 2.0329838 0.0485058 0.0498850 -3.793650 estrogen- ESRRA ILMN_167 0.0734263 8.1200845 2.1954264 0.0337986 0.0498850 -3.562120 metastasi MTA1 ILMN_174 0.0764830 8.0206056 2.4671966 0.0178449 0.0498850 -3.146276 transmem TMEM50A ILMN_320 0.0819119 8.0803616 2.2763211 0.0280697 0.0498850 -3.441938 translocas TIMM17B ILMN_169 0.0822428 8.1704049 2.2189925 0.0320311 0.0498850 -3.527435 GTP cyclo GCHFR ILMN_168 0.0830069 8.5393455 2.4615701 0.0180900 0.0498850 -3.155225 SNW dom SNW1 ILMN_181 0.0928481 8.7230223 2.0256929 0.0492802 0.0498850 -3.803724 mitogen- MAPK8IP3 ILMN_239 0.0931838 8.3026000 2.2372120 0.0307213 0.0498850 -3.500435 SP100 nuc SP100 ILMN_173 0.0979154 8.0883751 2.7161151 0.0095982 0.0498850 -2.737193 polymera POLR2C ILMN_174 0.0992158 9.2166100 2.3591247 0.0231197 0.0498850 -3.315711 LYR motif LYRM1 ILMN_170 0.1035905 8.0413202 2.0646931 0.0452595 0.0498850 -3.749513 Pim-3 pro PIM3 ILMN_176 0.1040625 10.433927 2.2377233 0.0306853 0.0498850 -3.499675 mannosid MAN2B2 ILMN_172 0.1108569 8.2472626 2.0303657 0.0487827 0.0498850 -3.797271 TSC22 do TSC22D4 ILMN_237 0.1117230 12.209808 2.0217046 0.0497084 0.0498850 -3.809223 lymphoto LTB ILMN_175 0.1122065 7.9781390 2.4420337 0.0189649 0.0498850 -3.186189 serine/thr STK11 ILMN_174 0.1143506 8.6084297 2.2631314 0.0289402 0.0498850 -3.461748 LYR motif LYRM5 ILMN_172 0.1156811 8.4901762 2.0222672 0.0496478 0.0498850 -3.808448 opioid gro OGFR ILMN_180 0.1176563 8.3087639 2.2441004 0.0302387 0.0498850 -3.490185 PR domai PRDM8 ILMN_218 0.1188162 8.1553656 2.1943560 0.0338809 0.0498850 -3.563689 tyrosyl-D TDP2 ILMN_166 0.1193275 8.6121837 2.3865082 0.0216646 0.0498850 -3.273273 lymphoto LTBR ILMN_176 0.1244890 8.4083169 2.2473633 0.0300124 0.0498850 -3.485322 CDC42 sm CDC42SE1 ILMN_330 0.1255624 8.0570225 2.1274319 0.0393919 0.0498850 -3.660658 small nucl SNRPB2 ILMN_175 0.1269725 9.3518646 2.0540845 0.0463238 0.0498850 -3.764337 chromoso C17orf62 ILMN_323 0.1271006 8.0208568 2.3445573 0.0239292 0.0498850 -3.338148 NEDD4 bi N4BP2L2 ILMN_180 0.1279882 9.7019723 2.1903051 0.0341940 0.0498850 -3.569622 linker for LAT2 ILMN_169 0.1301790 8.0900962 2.0547209 0.0462594 0.0498850 -3.763450 anti-silen ASF1B ILMN_180 0.1323150 9.9011219 2.1278856 0.0393521 0.0498850 -3.660008 major vau MVP ILMN_166 0.1325403 8.5902087 3.2934645 0.0020332 0.0498850 -1.702826 transmem TMEM101 ILMN_172 0.1399358 8.3306147 2.0766389 0.0440867 0.0498850 -3.732750 hexokinas HK2 ILMN_240 0.1419913 8.9781045 2.3033290 0.0263598 0.0498850 -3.401118 opiate rec OPRL1 ILMN_179 0.1454125 8.1009728 2.1949039 0.0338388 0.0498850 -3.562886 dehydrog DHRS13 ILMN_173 0.1461402 8.9535384 2.3307184 0.0247216 0.0498850 -3.359373 NEDD4 bi N4BP2L2 ILMN_176 0.1464082 9.0669900 2.0288382 0.0489448 0.0498850 -3.799381 tropomyo TPM3

ILMN_176 0.1466538 9.5252924 2.0674424 0.0449872 0.0498850 -3.745661 phosphati PIK3CD ILMN_233 0.1469065 8.5888531 2.9066428 0.0058472 0.0498850 -2.407937 protein ty PTK2B ILMN_165 0.1492599 9.0133867 2.1067129 0.0412511 0.0498850 -3.690224 interleuki IL4R ILMN_171 0.1504241 11.201696 2.4587204 0.0182153 0.0498850 -3.159752 glia matur GMFG ILMN_169 0.1517076 8.3945536 2.1079333 0.0411395 0.0498850 -3.688488 glucose-6 G6PD ILMN_166 0.1528331 9.3580201 2.1924993 0.0340241 0.0498850 -3.566409 neurobea NBEAL2 ILMN_215 0.1576729 9.7326606 2.2443316 0.0302226 0.0498850 -3.489840 SH3-doma SH3GLB2 ILMN_234 0.1584890 9.7694643 2.0241002 0.0494508 0.0498850 -3.805921 CDC42 sm CDC42SE1 ILMN_166 0.1590433 8.5414580 2.0815149 0.0436157 0.0498850 -3.725886 regulator RGS10 ILMN_176 0.1591847 8.3405100 2.0200686 0.0498850 0.0498850 -3.811476 SH3KBP1 SHKBP1 ILMN_167 0.1599778 9.5843979 2.2383535 0.0306409 0.0498850 -3.498738 DEAD (As DDX17 ILMN_175 0.1624460 8.1116476 2.2974788 0.0267221 0.0498850 -3.409989 purinergic P2RX1 ILMN_178 0.1627475 10.080125 2.4329011 0.0193869 0.0498850 -3.200606 sphingosi S1PR4 ILMN_180 0.1709895 8.5068140 2.5322016 0.0152243 0.0498850 -3.041905 acidic (leu ANP32A ILMN_175 0.1752870 8.6053661 2.6392240 0.0116645 0.0498850 -2.866232 phosphol LHPP ILMN_169 0.1823996 8.5668434 2.0887077 0.0429289 0.0498850 -3.715740 PDZ and LI PDLIM7 ILMN_177 0.1846646 8.7604725 2.4385644 0.0191242 0.0498850 -3.191670 phosphati PIK3CG ILMN_180 0.1869466 11.832632 2.0689719 0.0448363 0.0498850 -3.743517 interfero IFITM1 ILMN_174 0.1881447 9.6004962 2.0415504 0.0476094 0.0498850 -3.781777 ornithine ODC1 ILMN_211 0.1950111 8.3099497 2.1999408 0.0334535 0.0498850 -3.555497 Mediterra MEFV ILMN_178 0.1986055 8.6491728 2.2853117 0.0274898 0.0498850 -3.428388 patatin-li PNPLA2 ILMN_174 0.2069593 8.7342293 2.2704912 0.0284515 0.0498850 -3.450704 transmem TMEM8A ILMN_166 0.2861877 8.5561295 2.1449451 0.0378783 0.0498850 -3.635498 breakpoin BCR ILMN_179 0.3056316 9.2789307 2.3084072 0.0260489 0.0498850 -3.393405 glutamate GRINA ILMN_209 0.3087220 8.8115103 2.0815251 0.0436147 0.0498850 -3.725872 GATS prot GATSL3 ILMN_330 0.3224458 9.5651147 2.0419432 0.0475686 0.0498850 -3.781232 ornithine OAZ1 ILMN_178 0.3276898 10.662592 2.1446607 0.0379025 0.0498850 -3.635908 mitogen- MAP2K3 ILMN_179 0.3379969 8.1434616 2.7336293 0.0091774 0.0498850 -2.707482 transmem TMEM176A ILMN_168 0.3664972 9.8971072 2.8363756 0.0070340 0.0498850 -2.530887 coactivato CARM1 ILMN_205 0.3760748 8.0345099 2.0474332 0.0470022 0.0498850 -3.773602 interfero IFI27 ILMN_176 0.3969999 8.1043413 2.1015398 0.0417272 0.0498850 -3.697572 X inactive XIST ILMN_167 0.5625709 9.3996369 2.2481709 0.0299567 0.0498850 -3.484117 IKAROS fa IKZF1