Hippo Pathway Effectors YAP1/TAZ Induce a EWS-FLI1-Opposing Gene Signature and Associate With

Home , FLI1, WWTR1, ZNF43

bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

ORIGINAL ARTICLE

Hippo pathway effectors YAP1/TAZ induce a EWS-FLI1-opposing gene signature and associate with

disease progression in Ewing Sarcoma

Running title: TAZ/YAP1expression associates with disease progression in Ewing Sarcoma

Pablo Rodríguez-Núñeza1, Laura Romero-Pérezabc1*, Ana T. Amaralab, Pilar Puerto-Camachoab,

Carmen Jordánab, David Marcillaa, Thomas G. P. Grunewaldcde, Enrique de Alavaab*, Juan Díaz-

Martínab1*

1 Equal contribution

a Instituto de Biomedicina de Sevilla, CSIC-Universidad de Sevilla, Department of Pathology, Hospital

Universitario Virgen del Rocío, Seville, Spain.

b CIBERONC, ISCIII

cMax-Eder Research Group for Pediatric Sarcoma Biology Institute of Pathology. Faculty of Medicine, LMU

Munich, Munich, Germany.

d German Cancer Consortium (DKTK), partner site Munich, Munich, Germany.

e German Cancer Research Center (DKFZ), Heidelberg, Germany.

*Corresponding authors:

Enrique de Álava, [email protected]; Juan Díaz-Martín, [email protected]; Laura

Romero-Pérez, [email protected], [email protected]

1 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

Abstract

YAP1 and TAZ (WWTR1) oncoproteins are the final transducers of Hippo tumor suppressor pathway. Deregulation of the pathway leads to YAP1/TAZ activation fostering tumorigenesis in multiple malignant tumor types, including sarcoma. However, oncogenic mutations within the core components of the Hippo pathway are uncommon. Ewing Sarcoma (EwS), a pediatric cancer with low mutation rate, is characterized by a canonical fusion involving EWSR1 gene, and FLI1 as the most common partner. The fusion protein is a potent driver of oncogenesis but secondary alterations are scarce, and little is known about other biological factors that determine the risk of relapse or progression. We have observed YAP1/TAZ expression and transcriptional activity in EwS cell lines. Analyses of 55 primary human EwS samples revealed that high YAP1/TAZ expression was associated with progression of the disease and predicted poorer outcome.

We did not observe recurrent SNV or copy number gains/losses in Hippo pathway-related loci. However, differential CpG methylation of RASSF1 locus -a regulator of Hippo pathway- was observed in EwS cell lines compared with mesenchymal stem cells, the putative cell of origin of EwS. Hypermethylation of RASSF1 correlated with the transcriptional silencing of the tumor suppressor isoform RASFF1A, and transcriptional activation of the protumorigenic isoform RASSF1C promoting YAP1/TAZ activation. Knockdown of YAP1/TAZ decreased proliferation and invasion abilities of EwS cells, and revealed that YAP1/TAZ transcription activity is inversely correlated with the EWS-FLI1 transcriptional signature. This transcriptional antagonism could be partly explained by EWS-FLI1-mediated transcriptional repression of TAZ. Thus, YAP1/TAZ may override the transcriptional program induced by the fusion protein, contributing to the phenotypic plasticity determined by dynamic fluctuation of the fusion protein, a recently proposed model for disease dissemination in EwS.

Keywords: Ewing Sarcoma, Hippo pathway, metastasis, immunohistochemistry, transcriptional signatures

2 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

INTRODUCTION

Ewing Sarcoma (EwS) represents the second most common primary malignant bone tumor in children and young adults [1]. Owing to multimodal treatment concepts, 2/3 of the patients with localized disease achieve sustained remission but approximately 30 % relapse. Patients at relapse or with advanced disease have limited chance to survive with a three-year event free survival of less than 25% [2, 3]. While clinical prognostic markers such the presence of metastases or tumor volume are established, little is known about the biological factors determining the risk of progression, thus precluding risk-adapted therapeutic approaches. EwS was the first solid malignancy defined by the presence of tumor-specific EWSR1-ETS gene fusions [4], mainly EWSR1- FLI1 translocations, which are considered the main driver of the disease, but fusion type itself does not have any impact on disease progression [5]. As in most developmental cancers, additional recurrent mutations are scarce. The most common somatic mutations have been detected in STAG2, CDKN2A and TP53, associated with poor prognosis [6, 7]. Copy number variation studies by the PROVABES consortium using samples derived from the EURO-E.W.I.N.G.99 (EE99) and EWING 2008 trials showed that chromosome 1q gain and possibly chromosome 16q loss define patients with poor clinical outcome (Díaz-Martín et al, unpublished data), supporting previous retrospective studies [7, 8]. However, these secondary alterations occur with a frequency which does not account for the large proportion of patient who relapses.

The Hippo tumor suppressor pathway plays a critical role in tissue and organ size regulation by restraining cell proliferation and apoptosis under homeostatic conditions [9]. Central to Hippo pathway is a conserved cascade of adaptor proteins and inhibitory kinases that regulate the activity of the oncoproteins YAP1 and TAZ, the final effectors of this pathway in mammals. YAP1/TAZ do not directly bind DNA, but act as transcriptional coactivators of target genes involved in cell proliferation and survival through their interaction with transcriptional regulators such as TEAD factors [10]. The role of YAP1 and TAZ as important drivers in tumorigenesis has been extensively reported in carcinomas, and they also contribute to malignancies of mesenchymal origin [11-13]. In fact, given its key function in developmental processes, an important role has been inferred for Hippo signaling in pediatric cancer [14]. Despite this, somatic or germline mutations in Hippo pathway genes are uncommon, in comparison to other well-defined signaling pathways that are commonly disrupted in cancer [13, 15]. Since secondary genetic alterations are scarce in EwS, and given the established role of YAP1 and TAZ in cancer without engaging mutation, we aimed to explore the contribution of these factors to oncogenesis in Ewing sarcoma. Herein we evaluated a series of 55 EwS patients by immunohistochemistry (IHC) for expression/activation of YAP1 and TAZ. We observed a significant association of YAP1/TAZ nuclear expression and disease progression, as well as a potential mechanism of dysregulation involving epigenetic regulation of RASSF1 locus. Moreover, we demonstrated an interesting

3 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

interplay between TAZ/YAP1 function with the fusion protein, which fits into a recent model concept for metastatic spreading in EwS based on fluctuations of the expression of the fusion protein [16].

MATERIALS AND METHODS

Tumor samples

In this study we analyzed 88 formalin-fixed paraffin-embedded (FFPE) samples from 68 Ewing sarcoma patients (55 samples corresponding to primary tumor). We also analyzed a subset of 21 frozen samples from the same series. Clinical diagnosis of all the samples was performed according to the World Health Organization (WHO) classification [17], performing fluorescence in situ hybridization (FISH) to assess the presence of EwS translocation in tissue sections, which validates the immunohistochemical diagnosis. The only selection criteria were the availability of pathological data and tissue for tissue microarray (TMA) construction. Medical records were retrospectively reviewed and clinicopathologic information for 55 patients with primary tumor material were retrieved for further analyses (summarized in Table 1). Tissue samples were obtained from the HUVR-IBiS Biobank (Universitary Hospital Virgen del Rocio-Institute of Biomedicine of Seville Biobank. Andalusian Public Health System Biobank). This study was performed following the standard Spanish ethical regulations and it was approved by the corresponding ethics committee of the Hospital Virgen del Rocío de Sevilla and the Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI), Spain. Written informed consent was obtained from all patients and all clinical analyses were conducted in accordance with the principles of the Helsinki Declaration.

TMA construction and Immunohistochemistry

Representative tumor areas of EwS samples were selected on H&E-stained sections and two 1-mm diameter tissue cores were obtained from each specimen to set up 4 different TMAs. IHC was carried out on TMA sections using the Envision method (Dako, CA, USA) with a step of heat-induced antigen retrieval and using a primary antibody against YAP1 and TAZ (Suppl. Table 1). IHC staining was separately evaluated by two pathologists. YAP1/TAZ expression was evaluated for nuclear staining, thus focusing in their transcriptional activity. Tissue was given a score which resulted of multiplying the nuclear staining intensity from 0 (no staining) to 3 (strong staining), by the extension based on the percentage of positive cells (from 0 to 3). Samples were grouped as negative or weak positive (score 0-2), and strong positive (3-9).

4 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

Cell lines

EwS cell lines SKNMC, TTC-466, TC32, ,A4573, A673, CADO-ES, RD-ES, RM82, SKES1, STAET10, TC71 and WE68, were obtained from the EuroBoNet cell line panel [18]. MDA-MB-231, MCF7, RH30, SAOS2 and PC3 cell lines were purchased from ATCC. Primary human bone marrow mesenchymal cells (hMSC), immortalized with telomerase reverse transcriptase were provided by D. Campana [19].Each cell line was grown in its corresponding culture medium (DMEM, RPMI, EMEM or McCoy´s) supplemented with 10-15% of FBS (Fetal Bovine Serum) and 1% penicillin-streptomycin. We also used EwS cell line A673 engineered to express a doxycycline-inducible shRNA against the EWS-FLI1 fusion protein [20]. Cells were grown in DMEM supplemented with 10% fetal bovine serum, 100 μg/ml Zeocin (InvivoGen, ant-zn-5p) and 5 μg/ml Blasticidin (InvivoGen, ant-bl-10p). For the EWS-FLI1 shRNA induction, 1μg/ml doxycycline (Sigma, D9891) was added to the media for 48 hours.

Western Blotting

Western Blotting was performed to analyze the expression of different proteins by using primary antibodies detecting: YAP, SRC, Phospho-SRC, TAZ, CYR61, CTGF and Calnexin/GAPDH as endogenous controls. Antibodies details are provided in Supplementary Table 2. Blot detection was carried out by using Clarity western peroxide reagent (Bio-Rad Clarity western ECL substrate) and visualized by digital imaging in a Chemidoc Touch Imaging System (Bio-Rad).

Nucleus and cytoplasm subcellular fractionation

Cells (~9×106) were washed twice with ice-cold 1× PBS. Citoplasmic lysis buffer (HEPES pH 7,9, KCl 10 mM, EDTA 0,1 mM, EGTA 0,1 mM, PMSF 0,5 mM , DTT 1mM, NaF 1mM, Na3VO4 1mM, PIC 1x, Nonidet NP40x 0,625%) is added and attached cells were scraped off with a cell scraper. Cells were centrifugated for 2 minutes at 13000 RPM. Citoplasmic fraction-containing supernatant is placed in a different eppendorf and the nuclear fraction-containing pellet is resuspended in a Nuclear lysis buffer (HEPES pH 7,9 20 mM, NaCl 0,4M, EDTA 1 mM, EGTA 1 mM, PMSF 1mM, DTT 1mM, NaF 1mM, Na3VO4 1mM, PIC 1x) at 4ºC for 15 minutes with vortexing for 30 seconds every 5 minutes. After centrifugation for 5’ at 14000 RPM, nuclear fraction- containing supernatant was isolated.

5 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

Luciferase assays

Cells were seeded in 24 well plates 24h before transfection. The established YAP1/TAZ-TEAD responsive reporter 8xGTII–lux was a gift from Stefano Piccolo (Addgene plasmid # 34615) [21]. As negative control reporter we used pTNT-min (provided by Mark Bond [22]), lacking the TEAD elements. Luciferase reporters (400 ng/well) were transfected with Lipofectamine LTX with Plus Reagent (Thermo Fisher Scientific) together with pRL-TK Renilla (50 ng/well) to normalize for transfection efficiency. Cells were collected 24h after DNA transfection. Cell lysates were analysed using the Dual-Luciferase Reporter Assay System (Promega, #E1910). Luminiscence was measured using a TECAN infinite M200-PRO plate reader (Tecan, Männedorf, Switzerland).

siRNAs

Silencing of TAZ and YAP1 was performed by using 10nM Silencer Select siRNAs (Thermo Fisher Scientific), whose sequences are detailed in Suppl. Table 1. Viromer Blue was used as a transfection reagent according to the manufacturer´s conditions (Lipocalyx, Germany). We evaluated the eficiency of two different pairs of siRNAs targeting YAP1 and TAZ, and we confirmed similar results for both (Suppl. Fig. 4). We used a negative control designed against a non-human coding sequence (siC) and a positive control designed against GAPDH (siG).

Drugs

Dasatinib and pitavastatin were purchased from Selleckchem (Houston, TX, USA). Stock solutions of both compounds were prepared in dimethyl sulfoxide (DMSO) and diluted to final concentration in the culture medium. Controls were treated with DMSO at the same final concentration. The DMSO never exceeded 1:1000 (v/v) of total incubation volume and did not show any toxic effects on EwS cells.

Cell proliferation assay

Cell proliferation was evaluated using the ATP-lite 1 step Luminescence Assay System (Perkin Elmer). Cells were seeded in gelatin pre-treated 96 wells plates, avoiding marging areas, for at least 24 h. Culture medium was removed and ATP-lite solution was added. Luminiscence was measured using a TECAN infinite M200- PRO plate reader (Tecan, Männedorf, Switzerland).

6 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

Migration assay

Migration assay was performed as described previously [23]. Cells were grown on 6 wells plates to 85-90% confluence and a wound was made by scratching the monolayer of the cells. Pictures of the same selected area were taken after the times indicated and the percentage of wound healing was calculated using the imageJ software.

Invasion assay

Invasion assay was carried out on modified Boyden chambers (8 µm pore filters) from Cultrex (Trevigen). These chambers were coated with BME (Cultrex Basement Membrane Extract), a natural extracellular matrix hydrogel. It was diluted at 0.2X in coating buffer and added to the inserts 24 h before cells were seeded. Cells were cultured in medium without serum for at least 24 h before the assay. Afterwards, a volume of 100 µl of serum-free medium containing 1x105 cells was deposited on the top of the chamber. Serum was used as chemoattractant in the lower part of the chamber. After 48h at the incubator at 37C, both serum-free medium from the top and pure serum from the lower part of the chamber were removed. The top of the membrane was carefully cleaned and the bottom retaining invading cells was washed with PBS. Cells were fixed to the membrane with methanol 100% for 5 minutes at -20ºC. After PBS washing, cells were stained with DAPI and membranes were mounted on a slide to be observed under a fluorescence microscope (Olympus BX-61). Cell nucleus of the respective conditions were counted and compared with controls.

Transcriptome analysis

SK-N-MC cells were transfected with control or a combination of YAP1/TAZ siRNAs for 72h. Whole transcript expression analysis was conducted in four biological replicates of each sample. RNA was amplified and labeled using the GeneChip® WT PLUS Reagent Kit (Thermo Fisher Scientific, Inc.). Amplification was performed with 100 ng of total RNA input following procedures described in the WT PLUS Reagent Kit user manual. The amplified cDNA was quantified, fragmented, and labeled in preparation for hybridization to GeneChip® Human Transcriptome 2.0 Array (Thermo Fisher Scientific, Inc.) using 5.5 μg of single-stranded cDNA product and following protocols outlined in the user manual. Washing, staining (GeneChip® Fluidics Station 450, Thermo Fisher Scientific, Inc.), and scanning (GeneChip® Scanner 3000, Thermo Fisher Scientific, Inc.) were performed following protocols outlined in the user manual for cartridge arrays. The fluorescence signals scanned as DAT files were transformed to CEL files via the AGCC software (Thermo

7 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

Fisher Scientific, Inc.). The GeneChip® Command Console software (Thermo Fisher Scientific, Inc.) pretreated CEL files through robust multichip analysis algorithm to obtain CHP files. Next, CHP files were analyzed by Transcriptome Analysis Console (TAC) 4.0 software (Thermo Fisher Scientific, Inc.) which performs statistical analysis and provides a list of differentially expressed genes. Gene set enrichment analysis (GSEA v3.0) was performed to identify targets of YAP1/TAZ that are over-represented in previous defined gene sets [24, 25].

Genome-wide copy number analysis

FFPE samples were sliced into 10-μm sections and gDNA was extracted using the QIAamp DNA FFPE Tissue Kit (Qiagen, Sussex, United Kingdom). DNA concentration was determined using the Quant-iT™ PicoGreenR dsDNA Assay Kit (Thermo Fisher Scientific UK Ltd., Paisley, United Kingdom). Genome-wide copy number analysis was performed using the OncoScan FFPE Assay Kit (Affymetrix, Santa Clara, CA, USA) according to the manufacturer’s recommendations. Nexus Express for OncoScan 3 software (BioDiscovery, Hawthorne CA, USA) was used to estimate copy numbers. Significance testing for aberrant copy number (STAC) method was conducted to evaluate the significance of DNA copy number aberrations across the tumor series.

Methylation array Methylation data were generated as described in Puerto-Camacho et al. (2018) [26]. Data analyses (GSE118872) were performed using the Bioconductor lumi package [27].

Statistical analysis

Correlation between inmunohistochemical YAP1/TAZ expression and clinicopathological characteristics was assessed by chi-squared test for the categorical variables (summarized with percentages). Mann–Whitney test was used for the analysis of differences of the continuous variable age (summarized with means and standard errors). EwS-specific survival was defined as the time from surgery to the time of death from EwS with deaths from other causes being censored, whereas in time to relapse analysis, the end point was EwS recurrence, either local or distant. Survival curves were estimated using the Kaplan-Meier method, and the differences in survival were evaluated using the long-rank test. Cox`s proportional hazards modeling of parameters potentially related to survival were conducted to calculate hazard ratios (HR), in both univariate and multivariate analyses. All these statistical analyses were performed using SPSS version 20 (SPSS Inc., Chicago, IL, USA) and JMP 10 statistical software (SAS Institute Inc., Cary, NC, US). p< 0.05 was considered statistically significant.

Statistical analysis of in vitro functional assays was performed by using SPSS 20.0 (SPSS Inc., Chicago, IL, USA), and represented by graph tools from Excel (Microsoft Office v.10) or Origin Pro 9.0 software.

8 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

RESULTS

YAP1/TAZ are expressed in EwS cell lines and tumor specimens, and are associated with the presence of metastasis and poor prognosis.

First, we examined YAP1/TAZ expression by WB in 13 EwS cell lines with different pathognomonic gene fusions (Fig. 1A). We observed heterogeneous expression of both proteins across the cell line panel. Some of the EwS cell lines showed YAP1/TAZ expression comparable to cell lines in which a relevant role has been described for these factors (i.e. MDA-MB-231, a triple negative breast cancer cell line with NF2- mutations leading to activation of TAZ/YAP1) [28]. TAZ/YAP1 expression was also detected in human mesenchymal stem cells (hMSC) derived from bone marrow, a proposed cell of origin of EwS. Importantly, nuclear expression was observed by subcellular fractionation and immunofluorescence (Fig. 1B-C, Suppl. Fig. 1), suggesting functional transcriptional activity which was confirmed with luciferase reporter assays (Fig. 1D).

To test whether YAP1/TAZ abundance was associated with clinical variables in EwS, we analyzed their expression by IHC in a retrospective series of 55 primary tumors (Table 1). YAP1/TAZ strong expressing tumor cells exhibited intense nuclear staining with a variable signal in the cytoplasm (Fig. 2A). YAP1/TAZ expression was also observed in endothelial cells in negative samples providing an internal positive control for the IHC determination (Fig. 2B). YAP1/TAZ strong expression was associated to disease progression (chi- square test, p<0.0054), whereas no significant association was observed with age at surgery or location (Table 1). We also observed increased YAP1/TAZ positivity in metastatic or relapsed tumors in 11 patients with paired samples (Fig. 2C-H, 2I, paired t-test, p = 0.0204). Additional non-paired metastatic or relapsed tumor samples showed preferential strong expression as well (Fig. 2J, Fisher’s exact test, p = 0.006).

We retrieved follow-up data for the EwS patients with primary tumor biopsies to evaluate prognosis (median duration of follow-up of 35.23 months), but only 45 had known relapse date (median duration of follow-up of 41.43 months). YAP1/TAZ expression influenced significantly the time to relapse which was shorter in strong positive patients than in weak/negative patients (mean, 127.4 vs. 50.66 months, p=0.011, Fig. 2K). Similarly, Kaplan-Meier estimates of EwS specific survival were shorter (but not significant) for the YAP1/TAZ strong positive group compared with YAP1/TAZ weak/negative group (mean, 129.32 vs. 73.61 months, p=0.159, Fig. 2L). Accordingly, Cox regression univariate analyses determined that YAP1/TAZ strong expression was significantly correlated with the time to relapse but not with EwS specific survival, with the unadjusted hazard ratio (HR) being 3.354 (p=0.016) and 1.928 (p=0.167) respectively (Table 2). A significant correlation with survival and time to relapse was also observed for metastasis (Table 2). These variables were all included simultaneously, to assess the independent prognostic significance based on multivariate analysis. The adjusted HR of YAP1/TAZ strong expression for relapse did not reach significant confidence regarding time to

relapse, after controlling the Coxˈs regression model for the effects of age, tumor location and metastasis. However, a roughly significant HR for YAP1/TAZ was obtained in the multivariant analysis (Table 2).

Table 1. Clinical and pathologic findings according to YAP1/TAZ nuclear expression in primary EwS specimens (n=55)

TAZ/YAP1 expression (IHC)

Negative/Weak Strong Characteristics Analyzable p positive positive

Age (years) mean 55 20,72 (±2,062) 20,93 (±3,196) 0.9088

Location 42 0.4945 28 Bone 19 (67,86%) 9 (32,14%) (66,67%) 14 Soft tissue 8 (57,14%) 6 (42,86%) (33,33%)

Progression 50 0.0054

No 27 (54%) 21 (77,78%) 6 (22,22%)

Yes 23 (46%) 9 (39,13%) 14 (60,87%)

Table 2. Prognostic value of YAP1/TAZ IHC expression in relation to other clinical variables.

Time to relapse EwS-specific survival

Unadjusted HR Unadjusted HR Factors p Adjusted HR (95%CI) p p Adjusted HR (95%CI) p (95%CI) (95%CI)

TAZ/YAP1 (strong vs. 3,354 (1,253-8,974) 0.016 1,579 (0,287-8,676) 0.599 1,928 (0,761-4,886) 0.167 5,703 (1,004-32,400) 0.049 negative/weak)

77,954 (7,332- Metastasis 14,895 (4,675-47,455) <0,001 70,369 (4,980-994,326) 0.002 11,318 (3,211-39,895) <0,001 <0,001 828,754)

Age 0,967 (0,916-,1022) 0.234 1,034 (0,924-1,159) 0.557 0,970 (0,925-1,017) 0.208 0,971 (0,888-1,062) 0.523

Location (bone vs soft 2,491 (0,667-9,294) 0.174 2,612 (0,468-14,594) 0.274 1,066 (0,326-3,483) 0.916 2,640 (0,478 -14,570) 0.265 tissue)

10 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

Activation of YAP1 /TAZ in Ewing Sarcoma

We tried to determine the mechanisms that contribute to YAP1/TAZ activation in EwS. To do so, we interrogated public datasets for somatic mutations in the Hippo pathway-related genes, but we did not find any recurrent SNV (Supp. Fig. 2). Next, we analyzed copy number alterations in a series of 24 EwS by SNP arrays (Fig. 3). Gross chromosomal alterations were similar to previous reports, i.e. gains of whole chromosomes 8 and 12 [7]. Copy number gain in WWTR1 locus, with complete gain of chromosome 3 was detected in a single case. Gain at YAP1 locus was detected in another case with an almost tetraploid genotype. None of the two cases showed incremented mRNA expression associated to the copy number event. Regarding the core regulatory kinases of the Hippo pathway and other negative regulators of YAP1/TAZ function, no significant copy-loss events were observed (Fig. 3). Focal copy number aberration events in Hippo-related loci were also precluded after inspecting the data with the STAC algorithm (Suppl. Table 2).Similarly, Hippo-related loci were unaffected in a retrospective series of 165 cases of EwS, which was analyzed within the PROVABES consortium for validation of biomarkers in EwS (www.medizin.uni- muenster.de/provabes/network, Díaz-Martín J., unpublished data).

Deregulation of Hippo pathway leading to YAP1/TAZ activation could be the consequence of epigenetic silencing of tumor suppressor genes through DNA hypermethylation [11, 15, 29]. We inspected previous results of the group comparing CpG methylation in EwS cell lines versus human mesenchymal stem cells (hMSC) from EwS patients and healthy donors (GSE118872) [26] . Among the differentially methylated genes, we found that one of the negative regulators of YAP1/TAZ, RASSF1, was hypermethylated in EwS cells. No other Hippo-related loci showed differential methylation (Fig. 4A). Hypermethylation of RASSF1 accounts for silencing of RASSF1A transcript expression, but promotes switching to an alternative gene promoter driving the expression of the isoform RASSF1C. RASSF1A contributes to Hippo pathway-mediated repression of YAP1/TAZ, whereas RASSF1C promotes Src family kinases (SFKs)-mediated activation of YAP1 [30]. We confirmed expression of the alternate isoform RASSF1C in EwS cell lines, whereas RASSF1A expression was absent or reduced (with the exception of STAET-10 and TC-32 cell lines) compared with hMSC (Fig. 4B). Moreover, expression of YAP1/TAZ target genes positively correlated with RASSF1C expression in the cell line panel, as well as in EwS tumor specimens (Fig. 4C, D). Interestingly, TAZ but not YAP1 seems to be transcriptionally regulated since CTGF expression correlate with TAZ mRNA expression (Fig. 4D). Correlation of TAZ mRNA levels with Hippo target genes was also observed in larger EwS series in public repository expression data (Suppl. Fig. 3).

There is extensive evidence that Src can promote YAP/TAZ activity through a variety of mechanisms, i.e. Src, and other SFKs can directly phosphorylate YAP1 and TAZ promoting their activity and stability [31]. Therefore, since RASSF1C activates SFKs in RASSF1-methylated cells, we blocked SFK activity by exposing EwS cells

11 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

to dasatinib. Inhibition of SFKs resulted in reduced cell viability (SK-N-MC IC50=6,55 μM; TTC-466 IC50=2,11 μM) and upregulation of YAP1/TAZ target genes (Fig. 5A). Upon dasatinib treatment mRNA levels of YAP1 and TAZ remained unaffected, but TAZ protein expression was decreased and YAP1 inactivating phosphorylation increased in both cell lines (Fig. 5A). As an alternative approach of pharmacologic blockade of YAP1/TAZ activity we tested pitavastatin. Statins prevent nuclear localization of YAP1/TAZ via inhibition of the enzyme HMG-CoA reductase, ultimately affecting the metabolic control of YAP1/TAZ by the mevalonate pathway [32]. We also observed antiproliferative effect upon pitavastatin treatment (SK-N-MC IC50= 1,83 μM; TTC-466 IC50=1,86 μM), with mild reduction of YAP1/TAZ target genes and TAZ protein downregulation (Fig 5A). Neither dasatinib nor pitavastatin treatments affected EWS-FLI1 expression in SK-N-MC cell line, thus precluding the antiproliferative effect of these drugs to be mediated by the fusion protein.

YAP1/TAZ loss-of-function affects cell proliferation and invasion capacity in EwS cells

To assess the oncogenic properties of YAP1 and TAZ in EwS cells, we induced transient knockdown of YAP1, TAZ or simultaneous depletion of both factors, and evaluated cell proliferation, invasion and migration capacity of the silenced cells. We observed inhibition of proliferation in knockdown cells for every individual or combined siRNA transfection. Individual depletion of YAP1 inhibited cell growth more efficiently than TAZ silencing (Fig 5B). YAP1/TAZ silenced cells showed a significantly reduced invasive capacity as well (Fig 5C). Migration capacity of EwS cells upon YAP1/TAZ silencing was not significantly altered as compared to the control, but a slight trend towards diminished migration was observed in the doble-silenced cells (Suppl. Fig. 6).

YAP1/TAZ transcription activity is anti-correlated with EWS-FLI1 transcriptional signature

To evaluate the transcriptome modulation by YAP1/TAZ we conducted gene expression profiling by Affymetrix microarrays in SK-N-MC cells upon simultaneous silencing of both factors. We observed differential expression of 938 coding genes (Suppl. Table 3) including well-stablished YAP1/TAZ target genes, such as CYR61, CTGF or AMOT, which were confirmed by qPCR analyses in two EwS cell lines with different gene fusions (Fig. 6A). Similar results were obtained with individual silencing of each factor (Suppl. Fig. 5). Of note, expression levels of EWS-FLI1 were not affected in SK-N-MC (Fig. 6A) and other EwS cell lines tested (Suppl. Fig. 5).

Next, we collated this transcriptional profile with previously published curated gene sets. Interestingly, we found significant enrichment for several EwS-related gene signatures both in YAP1/TAZ-correlated and anticorrelated genes (Fig. 6C). YAP1/TAZ-anticorrelated genes were significantly over-represented among

12 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

EwS induced gene sets, and inversely YAP1/TAZ-correlated genes overlapped with EwS repressed genes. Thus, suggesting opposite transcriptional activity of EWS-FLI1 fusion gene and YAP1/TAZ factors. Accordingly, depletion of the EWS-FLI1 protein in the A673 EwS cell line resulted in the induction of YAP1/TAZ-regulated genes, as well as TAZ but not YAP1 factor (Fig. 6C, D). Therefore, transcriptional antagonism may be partially explained by EWS-FLI1-mediated downregulation of TAZ. We confirmed these observations in public datasets for EWS-FLI1 silencing in five EwS cell lines [33], and for ectopic expression of EWS-FLI1 in embryonic stem cells [34] (Suppl. Fig. 7). These observations are in accordance with recent reports describing that several genes are inversely regulated by TEAD factors and EWS-FLI1 [35, 36]. TEADs are the main transcription factors partners of YAP1 and TAZ, and usually associate with AP-1 transcription factors at distal enhancers [28, 37]. Both TEAD and AP-1 conserved binding motifs are present in EWS-FLI1 regulated genes [35]. Furthermore, EWS-FLI1 binding at WWTR1 locus coding for TAZ correlates with a decrease of TAZ mRNA expression, suggesting direct repression of TAZ by EWS-FLI1 (Suppl. Fig. 8).

Discussion

In the present study, we have shown that YAP1/TAZ expression associates with disease progression and poor prognosis in a large retrospective series of EwS patients. Few reports have addressed this issue so far, and the reported series were smaller, i.e. Ahmed AA. et al. [38] observed that YAP1 expression can be detected in 47% of samples (in a series of 32 cases) without association with survival, whereas in another study with only 5 cases, 60% and 80% showed YAP1 and TAZ expression respectively [39]. Other pediatric sarcomas such us rhabdomyosarcoma, osteosarcoma or neuroblastoma have been reported to express YAP1 and TAZ, with an impact in patient prognosis and conferring resistance to current therapies [40-44]. Another fact that supports the relevance of YAP1/TAZ and other Hippo signaling effectors in sarcomas is their involvement in recurrent fusion genes in certain histological types, such as epithelioid hemangioendothelioma (WWTR1-CAMTA1, YAP1-TFE3), epithelioid haemangioma (WWTR1-FOSB) or spindle cell rhabdomyosarcoma (VGLL2–CITED2, VGLL2–NCOA2, TEAD1–NCOA2)[45, 46]. Notwithstanding, aberrant activation of YAP1/TAZ in cancer is often promoted by mechanisms not involving somatic alterations. We have observed that epigenetic regulation of the RASSF1 locus could affect the expression of YAP1/TAZ target genes in EwS cell lines (Fig. 4). This result may explain previous observations describing a correlation of hypermethylation of RASSF1 and RASSF2 with worse clinical outcome in EwS [47, 48]. Moreover, Src kinase activation of invadopodia in response to stress in EwS [49] could be related to SFK-mediated activation of YAP1/TAZ by RASSF1C (Fig. 5A). However, YAP1/TAZ activation does not seem to rely on RASSF1 hypermethylation in hMSC (Fig. 4), the putative cell of origin of EwS, which exhibits high expression levels of YAP1 and TAZ (Fig. 1). Unaffected expression levels of YAP1 and derepression of TAZ upon EWS-FLI1 silencing (Fig. 6C, D) also supports the notion that both

13 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

factors are maybe expressed in the cell of origin, as proposed for ZEB2, an EMT (epithelial–mesenchymal transition) inducer like YAP1 and TAZ [50].

The association of YAP1/TAZ with metastatic spread could be arguably related to the relative levels of the fusion protein, recently reported to promote phenotypic plasticity of EwS cells [16]. In this scenario, YAP1/TAZ may promote a mesenchymal phenotype in EWS-FLI1 depleted EwS cells together with Wnt/beta-catenin [51], since it is well-established that the crosstalk between Hippo and wnt signaling is essential for tumor progression in several types of cancer [52]. As it has been described for Wnt/beta-catenin [51], the opposing transcriptional signature between YAP1/TAZ and EWS-FLI1 could partly contribute to the metastatic process. I.e. We found strong downregulation or upregulation of LOX (a mediator of metastasis [16]) in YAP1/TAZ- silenced or EWS-FLI1-silenced cells respectively. These results suggest that LOX expression in EwS could result both of derepression in a low-level state of the fusion protein as well as of inducer mechanisms involving YAP1 or TAZ. In line with this, ChIP-seq data from Bilke S. et al. [53] reveal that EWSR1-FLI1 binds at regulatory elements of some of the well-established TAZ/YAP1 target genes [36]. Furthermore, anticorrelation of AP-1 induced genes and EWSR1-FLI1 transcriptional signature was observed in the same cell model that we used in this work: inducible silencing of EWSR1-FLI1 in A673 cell line [36]. It is well established that YAP1/TAZ/TEAD transcriptional complexes usually cooperate with AP-1 at regulatory DNA modules to synergistically activate target genes [28, 37]. Therefore, the transcriptional antagonism might be consequence of some interference between YAP1/TAZ/TEAD-AP1 complexes and the fusion protein, as demonstrated by Katschnig et al. [35]. Another mechanism contributing to the opposing gene signatures might involve Ewing sarcoma-associated transcript 1 (EWSAT1), which was found to be significantly induced in YAP1/TAZ-silenced SK-N-MC cells (Suppl. Table 3). EWSAT1 is a long noncoding RNA that mediates EWS-FLI1 gene repression via interaction with a heterogeneous nuclear ribonucleoprotein [54]. In addition, we have observed inhibition of TAZ expression associated to the presence of EWS-FLI1, which also binds DNA at WWTR1 locus (Suppl. Fig. 8). Indeed, regulation of TAZ seems to occur at the transcriptional level, whereas YAP1 activity is not correlated with mRNA levels (Figs. 4C, 6E).

In summary, our study reveals that the interplay between Hippo pathway effectors YAP1/TAZ and the function of the gene fusion is relevant to shape the transcriptional program in EwS. The transcriptional output elicited by these factors deserves further characterization since our observations provide clinical evidence that YAP1/TAZ expression associates with disease progression in EwS patients. Studies with larger prospective series are needed in order to corroborate our observations and to stablish whether YAP1/TAZ could serve as reliable biomarkers to stratify and identify patients who could benefit from targeted therapies.

14 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

Acknowledgments

This research has been conducted using samples from the Hospital Universitario Virgen del Rocío-Instituto de Biomedicina de Sevilla Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos PT17/0015/0041). The authors thank the donors for the human specimens used in this study. This work was supported by a grant from the Fundación Pública Andaluza Progreso y Salud (Junta de Andalucía) and JANSSEN CILAG, S.A. (Grant No. PI-0344-2014) to JDM. PRN is a PhD student recipient of a PFIS fellowship to Enrique de Alava (Grant No. F109/00193). JDM, LRP and ATM are PhD researchers funded by the Asociación Española Contra el Cáncer (aecc, GCB13-1578). CJ works as a laboratory technician supported by the ISCIII. EDA’s lab is supported by the AECC project (GCB13-1578); ISCIII-FEDER (PI14/01466); CIBERONC (CB16/12/00361), Asociación Pablo Ugarte and Fundación María García Estrada . The laboratory of TGPG is supported supported by the ‘Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultät der LMU München’ (WiFoMed), by LMU Munich’s Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative, the ‘Mehr LEBEN für krebskranke Kinder – Bettina-Bräu-Stiftung’ (to TGPG), the Fritz-Thyssen Foundation (FTF-40.15.0.030MN), the Kind- Philipp-Foundation, the Matthias-Lackas Foundation, the Dr. Leopold and Carmen Ellinger Foundation, the Wilhelm-Sander-Foundation (2016.167.1), the German Cancer Aid (DKH-70112257), the Gert und Susanna Mayer Foundation, and the Deutsche Forschungsgemeinschaft (DFG-391665916).

The authors thank Dr. Javier Alonso for providing the cell line A673 transfected with a inducible shRNA against EWS-FLI1. We also thank Dr. Stefano Piccolo for the luciferase reporter plasmid with TEAD motifs (Addgene plasmid # 34615), Dr. Mark Bond for providing the plasmid pTNT-min, and D. Campana for hMSC TERT cell line.

Author contributions

JDM, PRN and LRP contribute equally to this work and were responsible for the experimental design and the undertaking of the experiments. EA and DM reviewed the pathologic and immunohistochemical analyses, and the clinical data. ATM, PPC and CJ carried out some of the experiments. JDM, LRP, and PRN performed the statistical analysis and interpreted the data. TGPG analyzed public datasets. JDM designed the study, and LRP, EA and JDM were involved in writing the paper. JDM generated the figures and drafted the manuscript. All authors contributed to the editing of the manuscript and gave their approval of the final version.

15 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

References

1. Choi EY, Gardner JM, Lucas DR, et al. Ewing sarcoma. Semin Diagn Pathol 2014; 31: 39-47. 2. Grunewald TGP, Cidre-Aranaz F, Surdez D, et al. Ewing sarcoma. Nat Rev Dis Primers 2018; 4: 5. 3. Gorlick R, Janeway K, Lessnick S, et al. Children's Oncology Group's 2013 blueprint for research: bone tumors. Pediatr Blood Cancer 2013; 60: 1009-1015. 4. Delattre O, Zucman J, Plougastel B, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 1992; 359: 162-165. 5. Le Deley MC, Delattre O, Schaefer KL, et al. Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial. J Clin Oncol 2010; 28: 1982-1988. 6. Crompton BD, Stewart C, Taylor-Weiner A, et al. The genomic landscape of pediatric Ewing sarcoma. Cancer Discov 2014; 4: 1326-1341. 7. Tirode F, Surdez D, Ma X, et al. Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov 2014; 4: 1342-1353. 8. Mackintosh C, Ordonez JL, Garcia-Dominguez DJ, et al. 1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma. Oncogene 2012; 31: 1287-1298. 9. Dong J, Feldmann G, Huang J, et al. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 2007; 130: 1120-1133. 10. Zhao B, Tumaneng K, Guan KL. The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal. Nat Cell Biol 2011; 13: 877-883. 11. Deel MD, Li JJ, Crose LE, et al. A Review: Molecular Aberrations within Hippo Signaling in Bone and Soft-Tissue Sarcomas. Front Oncol 2015; 5: 190. 12. Barron DA, Kagey JD. The role of the Hippo pathway in human disease and tumorigenesis. Clin Transl Med 2014; 3: 25. 13. Harvey KF, Zhang X, Thomas DM. The Hippo pathway and human cancer. Nat Rev Cancer 2013; 13: 246-257. 14. Ahmed AA, Mohamed AD, Gener M, et al. YAP and the Hippo pathway in pediatric cancer. Mol Cell Oncol 2017; 4: e1295127. 15. Johnson R, Halder G. The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat Rev Drug Discov 2014; 13: 63-79. 16. Franzetti GA, Laud-Duval K, van der Ent W, et al. Cell-to-cell heterogeneity of EWSR1-FLI1 activity determines proliferation/migration choices in Ewing sarcoma cells. Oncogene 2017; 36: 3505-3514. 17. Jo VY, Fletcher CD. WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition. Pathology 2014; 46: 95-104. 18. Ottaviano L, Schaefer KL, Gajewski M, et al. Molecular characterization of commonly used cell lines for bone tumor research: a trans-European EuroBoNet effort. Genes Chromosomes Cancer 2010; 49: 40-51. 19. Mihara K, Imai C, Coustan-Smith E, et al. Development and functional characterization of human bone marrow mesenchymal cells immortalized by enforced expression of telomerase. Br J Haematol 2003; 120: 846-849. 20. Carrillo J, Garcia-Aragoncillo E, Azorin D, et al. Cholecystokinin down-regulation by RNA interference impairs Ewing tumor growth. Clin Cancer Res 2007; 13: 2429-2440. 21. Dupont S, Morsut L, Aragona M, et al. Role of YAP/TAZ in mechanotransduction. Nature 2011; 474: 179-183.

16 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

22. Kimura TE, Duggirala A, Smith MC, et al. The Hippo pathway mediates inhibition of vascular smooth muscle cell proliferation by cAMP. J Mol Cell Cardiol 2016; 90: 1-10. 23. Moreno-Bueno G, Peinado H, Molina P, et al. The morphological and molecular features of the epithelial-to-mesenchymal transition. Nat Protoc 2009; 4: 1591-1613. 24. Subramanian A, Tamayo P, Mootha VK, 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: 15545-15550. 25. Mootha VK, Lindgren CM, Eriksson KF, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 2003; 34: 267-273. 26. Puerto-Camacho P, Amaral AT, Lamhamedi-Cherradi SE, et al. Preclinical Efficacy of Endoglin- Targeting Antibody-Drug Conjugates for the Treatment of Ewing Sarcoma. Clin Cancer Res 2018. 27. Du P, Kibbe WA, Lin SM. lumi: a pipeline for processing Illumina microarray. Bioinformatics 2008; 24: 1547-1548. 28. Zanconato F, Forcato M, Battilana G, et al. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat Cell Biol 2015; 17: 1218-1227. 29. Sanchez-Vega F, Mina M, Armenia J, et al. Oncogenic Signaling Pathways in The Cancer Genome Atlas. Cell 2018; 173: 321-337 e310. 30. Vlahov N, Scrace S, Soto MS, et al. Alternate RASSF1 Transcripts Control SRC Activity, E-Cadherin Contacts, and YAP-Mediated Invasion. Curr Biol 2015; 25: 3019-3034. 31. Warren JSA, Xiao Y, Lamar JM. YAP/TAZ Activation as a Target for Treating Metastatic Cancer. Cancers (Basel) 2018; 10. 32. Sorrentino G, Ruggeri N, Specchia V, et al. Metabolic control of YAP and TAZ by the mevalonate pathway. Nat Cell Biol 2014; 16: 357-366. 33. Kauer M, Ban J, Kofler R, et al. A molecular function map of Ewing's sarcoma. PLoS One 2009; 4: e5415. 34. Gordon DJ, Motwani M, Pellman D. Modeling the initiation of Ewing sarcoma tumorigenesis in differentiating human embryonic stem cells. Oncogene 2016; 35: 3092-3102. 35. Katschnig AM, Kauer MO, Schwentner R, et al. EWS-FLI1 perturbs MRTFB/YAP-1/TEAD target gene regulation inhibiting cytoskeletal autoregulatory feedback in Ewing sarcoma. Oncogene 2017; 36: 5995-6005. 36. Tomazou EM, Sheffield NC, Schmidl C, et al. Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1. Cell Rep 2015; 10: 1082-1095. 37. Liu X, Li H, Rajurkar M, et al. Tead and AP1 Coordinate Transcription and Motility. Cell Rep 2016; 14: 1169-1180. 38. Ahmed AA, Abedalthagafi M, Anwar AE, et al. Akt and Hippo Pathways in Ewing's Sarcoma Tumors and Their Prognostic Significance. J Cancer 2015; 6: 1005-1010. 39. Fullenkamp CA, Hall SL, Jaber OI, et al. TAZ and YAP are frequently activated oncoproteins in sarcomas. Oncotarget 2016; 7: 30094-30108. 40. Mohamed A, Sun C, De Mello V, et al. The Hippo effector TAZ (WWTR1) transforms myoblasts and TAZ abundance is associated with reduced survival in embryonal rhabdomyosarcoma. J Pathol 2016; 240: 3-14. 41. Tremblay AM, Missiaglia E, Galli GG, et al. The Hippo transducer YAP1 transforms activated satellite cells and is a potent effector of embryonal rhabdomyosarcoma formation. Cancer Cell 2014; 26: 273- 287. 42. Bouvier C, Macagno N, Nguyen Q, et al. Prognostic value of the Hippo pathway transcriptional coactivators YAP/TAZ and beta1-integrin in conventional osteosarcoma. Oncotarget 2016; 7: 64702- 64710.

17 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

43. Schramm A, Koster J, Assenov Y, et al. Mutational dynamics between primary and relapse neuroblastomas. Nat Genet 2015; 47: 872-877. 44. Deel MD, Slemmons KK, Hinson AR, et al. The Transcriptional Coactivator TAZ Is a Potent Mediator of Alveolar Rhabdomyosarcoma Tumorigenesis. Clin Cancer Res 2018; 24: 2616-2630. 45. Schaefer IM, Fletcher CDM. Recent advances in the diagnosis of soft tissue tumours. Pathology 2018; 50: 37-48. 46. Suurmeijer AJH, Kao YC, Antonescu CR. New advances in the molecular classification of pediatric mesenchymal tumors. Genes Chromosomes Cancer 2018. 47. Gharanei S, Brini AT, Vaiyapuri S, et al. RASSF2 methylation is a strong prognostic marker in younger age patients with Ewing sarcoma. Epigenetics 2013; 8: 893-898. 48. Avigad S, Shukla S, Naumov I, et al. Aberrant methylation and reduced expression of RASSF1A in Ewing sarcoma. Pediatr Blood Cancer 2009; 53: 1023-1028. 49. Bailey KM, Airik M, Krook MA, et al. Micro-Environmental Stress Induces Src-Dependent Activation of Invadopodia and Cell Migration in Ewing Sarcoma. Neoplasia 2016; 18: 480-488. 50. Wiles ET, Bell R, Thomas D, et al. ZEB2 Represses the Epithelial Phenotype and Facilitates Metastasis in Ewing Sarcoma. Genes Cancer 2013; 4: 486-500. 51. Pedersen EA, Menon R, Bailey KM, et al. Activation of Wnt/beta-Catenin in Ewing Sarcoma Cells Antagonizes EWS/ETS Function and Promotes Phenotypic Transition to More Metastatic Cell States. Cancer Res 2016; 76: 5040-5053. 52. Noguchi S, Saito A, Nagase T. YAP/TAZ Signaling as a Molecular Link between Fibrosis and Cancer. Int J Mol Sci 2018; 19. 53. Bilke S, Schwentner R, Yang F, et al. Oncogenic ETS fusions deregulate E2F3 target genes in Ewing sarcoma and prostate cancer. Genome Res 2013; 23: 1797-1809. 54. Marques Howarth M, Simpson D, Ngok SP, et al. Long noncoding RNA EWSAT1-mediated gene repression facilitates Ewing sarcoma oncogenesis. J Clin Invest 2014; 124: 5275-5290.

18 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

Figure 1. YAP1 and TAZ are expressed and active in EwS cell lines. (A) Western blot using a monoclonal antibody recognizing total levels of YAP1 and TAZ proteins in a panel of 13 EwS cell lines. Basal and luminal breast cancer (MDA- MB-231, MCF-7), prostate cancer (PC3), osteosarcoma (SA-OS-2), rhabdomyosarcoma (RH30) and human mesenchymal stem cells (hMSC) were included in the assay.(B) Nucleus and cytoplasm subcellular lysates were assessed by WB (T, Total extract; N, nucleus; C, cytoplasm). (C) Immunofluorescence microscopy with the indicated antibodies (60X). (D) YAP1/TAZ-TEAD dependent transcriptional activity in EwS cell lines was evaluated with luciferase reporter constructs containing sequences with or without TEAD elements (8xTEAD and TnT-minP constructs respectively). RLU (Relative luminescence units) was normalized to renilla luciferase values. Data are represented as mean ±SE of 3 biological replicates.

Figure 2. YAP1/TAZ expression associates with disease progression. (A) Representative image for YAP1/TAZ strong positive expression in a primary EwS tumor (40x). (B) Staining of endothelial cells can be observed in a negative tumor specimen. (C-H) Immunostaining for YAP1/TAZ in primary tumors (left) and matched metastasis (right) of the same patients (40x). (I) Comparison of YAP1/TAZ immunostaining in 11 matched biopsies. (J) Distribution of samples in each tumor category (primary vs metastasis or relapse) according to YAP1/TAZ staining score. The number of samples is indicated on the bars. (K, L) Kaplan-Meier survival curves for YAP1/TAZ protein expression in EwS patients grouped as negative/weak positive vs strong positive staining.

Fig. 3. Summary of copy number aberrations detected in 24 EwS samples. Frequencies of copy number gain (above axis, blue) and copy number loss (below axis, red) across the human genome. Hippo-related loci are indicated: Tumor suppressor genes such us core kinases of the pathway are marked in black, and oncogenes WWTR1 and YAP1 in red.

Fig. 4. DNA methylation profiling of EwS cell lines and MSCs revealed differential CpG methylation in RASSF1 locus. (A) Heat map depicting CpG methylation levels of Hippo-related loci across a panel of EwS cell lines and hMSC from EwS patients and healthy donors. (B) Relative quantification by qPCR of RASS1A and RASSF1C transcripts and TAZ/YAP1 target genes in a panel of EwS cell lines. A basal breast cancer cell line and hMSC are included as controls (experiments were performed with 3 biological samples in triplicates). (C) Correlation analyses of mRNA expression levels (qPCR) of CTGF with RASSF1C, TAZ and YAP1 (r, Pearson’s correlation coefficient).

Fig 5. Pharmacologic inhibition and siRNA silencing of YAP1/TAZ in EwS cells. (A) SK-N-MC and TTC-466 cell lines were treated with Dasatinib (D, 1 uM) or Pitavastatin (P, 1 uM) during 24h, and mRNA levels of YAP1, TAZ and their target genes CTGF and CYR61 were quantified by qPCR. mRNA levels of EWS-FLI1 were evaluated in SK-N-MC cell line. Whole cell extracts were also analyzed by WB (experiments were performed with 3 biological samples in tripli cates; *p<0.05). (B) Proliferation curves of EwS cell lines transfected with control siRNA (C), siRNA targeting YAP1 (siY), TAZ (siT) or a combination of siRNAs to deplete both factors simultaneously (siYT). Two different siRNAs were used to knockdown each factor rendering similar levels of silencing (Suppl. Fig. 4), data are only shown for one of the siRNAs. Results are expressed as the mean ± SD of three independent experiments performed in triplicate. All the conditions were significantly different form the control (p<0.05) (C) Invasion assay of EwS cell lines upon individual or combined silencing of YAP1 and TAZ (*p<0.05, **p<0.005).

Figure 6. YAP1/TAZ induce an EWS-FLI1-oppossite gene signature. (A) qPCR assays for YAP1/TAZ target genes in EwS cell lines with different gene fusions upon siRNA depletion of YAP1 and TAZ (see Suppl Fig. x. for qPCR with individual silencing of each factor). (B) EwS gene sets with a positive and negative enrichment score for YAP1/TAZ regulated genes in SK-N-MC cell line. (C, D) Examples of YAP1/TAZ rank-ordered target genes compared with downregulated and upregulated EWS-FLI1 gene sets respectively (NES, normalized enrichment score). (E) qPCR and WB assays showing derepression of TAZ and YAP1/TAZ target genes upon silencing of EWS-FLI1 in the cell line A673 (dox, doxycycline induction of shRNA targeting EWS-FLI1).

Supplementary Table 1

Antibodies and siRNAs, suppliers and dilutions.

Marker Antibody Supplier Application Dilution WB Rabbit monoclonal anti-YAP/TAZ Cell signaling WWTR1/TAZ IHC (epitope 1/1000 1/50 (D24E4) Technology retrieval: citrate) Mouse monoclonal anti-YAP Santa Cruz YAP1 WB 1/100 (63.7):sc-101199 Biotechnology Rabbit polyclonal anti-Phospho- Cell signaling Phospho-YAP WB 1/500 YAP (Ser127) Technology Phospho-Src Rabbit polyclonal anti-Phopho-Src Cell signaling WB 1/1000 Family Family (Tyr416) Technology Rabbit monoclonal anti-Src Cell signaling Src WB 1/1000 (36D10) Technology Rabbit monoclonal anti-CYR61 Cell signaling CYR61 WB 1/1000 (D4H5D) XP Technology Mouse monoclonal anti- Santa Cruz Calnexin WB 1/1000 Calnexin(E-10) sc-46669 Biotechnology Rabbit monoclonal anti- Cell signaling GAPDH WB 1/1000 GAPDH(D16H11) Technology Rabbit Anti-Human Fli-1 Polyclonal FLI MyBiosource WB 1/1000 Antibody

siRNAs (Thermo Fisher Scientific) Name siRNA sequences (5' to 3')

siYAP1 GACAUCUUCUGGUCAGAGAtt

siTAZ1 ACGUUGACUUAGGAACUUUtt siYAP2 CUGGUCAGAGAUACUUCUUtt

siTAZ2 AGGUACUUCCUCAAUCACAtt siC Silencer™ Select Negative Control1 # 4390843 siGAPDH Silencer™ Select GAPDH Positive Control #4390849

Suppl Table 2. STAC peaks identified in 24 EwS samples Displaying only significant regions with p-value less than or equal to 0.05

Region Region Length Cytoband Location Event P-Value Genes chr1:17,769,898-17,867,479 97581 p36.13 CN Loss 0 1 chr1:110,245,941-110,254,909 8968 p13.3 CN Gain 0.032 1 chr1:145,115,883-145,284,177 168294 q21.1 CN Gain 0.048 5 chr2:89,450,331-91,866,487 2416156 p11.2 - p11.1 CN Gain 0.012 1 chr8:39,240,734-39,379,305 138571 p11.22 CN Loss 0 2 chr8:144,973,902-145,599,396 625494 q24.3 CN Gain 0.005 31 chr9:21,922,941-21,998,297 75356 p21.3 CN Loss 0.001 3 chr9:21,972,663-21,987,472 14809 p21.3 CN Gain 0.009 1 chr11:69,435,792-69,448,373 12581 q13.3 CN Gain 0.035 0 chr11:69,450,394-69,471,746 21352 q13.3 CN Gain 0 1 chr12:58,124,935-58,135,420 10485 q14.1 CN Gain 0 1 chr14:106,829,127-107,013,827 184700 q32.33 CN Gain 0.01 1 chr16:1,154,125-1,365,967 211842 p13.3 CN Gain 0 6 chr19:1,224,518-1,254,735 30217 p13.3 CN Gain 0.046 4 chr19:33,689,978-33,768,782 78804 q13.11 CN Gain 0.001 2 chr22:24,346,428-24,390,318 43890 q11.23 CN Loss 0 5

Suppl. Fig.1. Immunofluorescence microscopy with the indicated antibodies (60X).

Suppl. Fig. 2. Hippo pathway-associated genes do not harbor recurrent mutations in EwS cell lines and patients. Mutational profile in different gene sets across 112 ES patients (Institut Curie; PMID: 25223734)(A) 92 EwS patients (Dana-Farber Cancer Institute; PMID: 25186949) (B) and 11 EwS cell lines (Dana-Farber Cancer Institute; PMID: 25186949 ) (C). Cell lines were, in order: A673, TC71, TTC466, EW8, EWS834, EWS502, RDES, TC32, CHLA258, CADO-ES and SKNEP1. Each EwS patient/cell line is represented by a grey bar. D. Genetic mutation frequency (%) at indicated gene sets across different studies. bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

Suppl. Fig. 3. WWTR1 (TAZ) expression correlates with EWS-FLI1 targets in EwS patients.

Suppl. Fig. 4. Western blot assay to test silencing of YAP1 and TAZ in SK-N-MC cell line with two different siRNAs in individual or doble trasfection. -, non transfected; C Sramble siRNA; G, siRNA targeting GAPDH; T1 and T2, siRNAs targeting TAZ; Y1 and Y2, siRNAs targeting YAP1; YT1, combination of siRNAs T1 and Y1; YT2, combination of siRNAs T2 and Y2.

Suppl. Fig. 5. (A) qPCR for quantification of YAZ1/TAZ target genes in SK-N-MC cell line upon siRNA silencing of YAP1 and TAZ. (B) Lysates from TC-32 and SK-N-MC silenced cells were probed with anti-FLI1 to evaluate EWS-FLI1 protein expression.

Suppl. Fig. 6. Representative images of a wound healing assay using control or YAP1/TAZ-silenced TTC-466 cells.

A B

Supp Fig. 7. EWS-FLI1 modulates WWTR1 (TAZ) and Hippo target genes expression in different in vitro models. A. Analysis of gene expression levels of YAP1, WWTR1, CYR61 and CTGF after shRNA-mediated knockdown (kd) of EWSR1-FLI1 in 5 ES cell lines (WE68, SK-N-MC, TC252, STA-ET-1, STA-ET-7.2) (GSE14543). Data are represented in a before-after plot in which each dot represents a cell line. Two-tailed student’s t test. B. Analysis of gene expression levels of WWTR1, YAP1, TAZ/YAP1 targets (CYR61, CTGF), EWS-FLI1-repressed (LOX, TGFBRII, CDKN1A) and - induced targets (NR0B1, EZH2, ID2, CAV1, SPARC) and CD99 expression in human embryonic stem cells after ectopic expression of EWSR1-FLI1 (GSE64686). Mean±S.E.M are depicted of the three biological triplicates for each gene. Two- tailed student’s t test.

Suppl. Fig. 8. Genome browser screenshot of WWTR1 locus showing RNA expression upon inducible silencing of EWS- FLI in A673 cell line. EWS-FLI binding peaks within the locus are depicted and nucleotide sequence is indicated for one peak with ETS binding motifs. Data were retrieved from http://tomazou2015.computational-epigenetics.org [36]. bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not Supplementarycertified Table by3. peerGenes review) modulated is the author/funder. by YAP1/TAZ All rights (siControl reserved. No vs reuse siYAP1/TAZ) allowed without permission.

Gene Symbol Fold Change P-val FDR P-val Description Cytoband mRNA Accession YAP1 2.42 1.10E-08 0.0007 Yes-associated11q13 protein 1 NM_001130145; NM_001195044; NM_001195045; NM_006106; ENST00000282441; ENST00000345877; ENST00000524575; ENST00000526343; ENST00000528834; ENST00000531439; ENST00000537274; AB567720; AK304485; AL832620; BC038235; uc001pgt.3; uc001pgu.3; uc001pgv.3; uc001pgw.2; uc010ruo.2; uc010rup.1; uc021qpf.1; ENST00000445250 KRT10 -6.45 3.61E-08 0.0012 keratin 10, type17q21 I NM_000421; ENST00000269576; BC034697; OTTHUMT00000257875; uc002hvi.3; ENST00000459776 CYR61 1.97 4.79E-07 0.0108 cysteine-rich, angiogenic1p22.3 inducer,NM_001554; 61 ENST00000451137; ENST00000480413; AL832891; BC001271; BC009199; BC016952; OTTHUMT00000029187; OTTHUMT00000029188; uc001dle.3; ENST00000360431; ENST00000536321; uc021opf.1 GDAP1 -1.98 1.82E-06 0.0307 ganglioside induced8q21.11 differentiationNM_001040875; associated NM_018972;protein 1 ENST00000220822; ENST00000434412; ENST00000521096; AK295594; BC024939; OTTHUMT00000379059; OTTHUMT00000379060; OTTHUMT00000379061; OTTHUMT00000379062; OTTHUMT00000379063; OTTHUMT00000379064; OTTHUMT00000379065; OTTHUMT00000379066; uc003yah.3; uc011lfj.2; uc003yai.3 MAT2B 1.6 2.99E-06 0.0363 methionine adenosyltransferase5q34 NM_013283; II, beta NM_182796; ENST00000280969; ENST00000321757; ENST00000518095; ENST00000521838; AB073390; BC005218; BC066645; BC093030; DQ413182; OTTHUMT00000252748; OTTHUMT00000252749; OTTHUMT00000374157; OTTHUMT00000374158; OTTHUMT00000374160; OTTHUMT00000374194; OTTHUMT00000374195; OTTHUMT00000374196; ENST00000415433; ENST00000518731; OTTHUMT00000374193; uc003lzj.3; uc003lzk.3; uc003lzl.1; uc003lzm.3 CXCL10 -2.82 3.22E-06 0.0363 chemokine (C-X-C4q21 motif) ligandNM_001565; 10 ENST00000306602; BC010954; OTTHUMT00000362817; uc003hjl.4 BOD1 -1.66 4.22E-06 0.0392 biorientation of5q35.2 chromosomesNM_001159651; in cell division 1 NM_138369; ENST00000285908; ENST00000311086; ENST00000471339; ENST00000480951; BC003114; BC007436; OTTHUMT00000252963; OTTHUMT00000351715; OTTHUMT00000351716; OTTHUMT00000351717; OTTHUMT00000351718; OTTHUMT00000351719; OTTHUMT00000376472; uc003mcq.2; uc003mcr.2 NR4A3 -1.47 5.00E-06 0.0392 nuclear receptor9q22 subfamily 4,NM_006981; group A, member NM_173199; 3 NM_173200; ENST00000330847; ENST00000338488; ENST00000395097; uc004bae.3; uc004baf.1; uc022bky.1; ENST00000395096; OTTHUMT00000055482; OTTHUMT00000055483; OTTHUMT00000055484 SOGA3; KIAA0408 -1.54 5.41E-06 0.0392 SOGA family member6q22.33 3; KIAA0408NM_001012279; NM_014702; ENST00000481848; ENST00000483725; ENST00000556132; AB007868; AK125983; AK127114; BC018396; OTTHUMT00000042139; OTTHUMT00000042140; OTTHUMT00000042145; OTTHUMT00000042146; OTTHUMT00000042148; OTTHUMT00000042150; uc003qba.3; uc003qbb.3; uc003qbc.3; uc003qbd.3; uc011ebs.2; ENST00000368268; ENST00000465909; ENST00000525778; OTTHUMT00000042141; OTTHUMT00000042142; OTTHUMT00000042147; OTTHUMT00000042149 CFH 1.7 5.86E-06 0.0392 complement factor1q32 H NM_000186; NM_001014975; ENST00000359637; ENST00000367429; ENST00000496761; AK225649; BC012610; BC142699; OTTHUMT00000086412; OTTHUMT00000087502; OTTHUMT00000087503; OTTHUMT00000088705; OTTHUMT00000317692; uc001gti.4; uc001gtj.4; uc009wyw.3; uc009wyx.3; ENST00000391986; ENST00000439155 E2F2 -1.63 7.43E-06 0.0392 E2F transcription1p36 factor 2 NM_004091; ENST00000361729; ENST00000487237; BC053676; OTTHUMT00000008885; OTTHUMT00000008886; uc001bhe.2 ANXA1 1.86 7.55E-06 0.0392 annexin A1 9q21.13 NM_000700; ENST00000257497; ENST00000376911; ENST00000491192; AK074480; BC001275; BC035993; OTTHUMT00000052663; OTTHUMT00000052664; OTTHUMT00000052665; OTTHUMT00000052666; OTTHUMT00000052667; OTTHUMT00000052668; OTTHUMT00000052669; OTTHUMT00000052670; uc004ajf.1; uc004ajg.1 WSB1 -1.56 7.84E-06 0.0392 WD repeat and17q11.1 SOCS box containingNM_015626; 1 NM_134265; ENST00000262394; ENST00000348811; ENST00000427287; ENST00000467843; AK294516; AK300262; AK307114; BC021110; BC048007; OTTHUMT00000255391; OTTHUMT00000255392; OTTHUMT00000255393; OTTHUMT00000255394; uc002gzd.1; uc002gze.1; uc002gzf.1; uc010crf.1; uc010vzy.1; uc010vzz.1 TNFAIP3 -1.54 8.13E-06 0.0392 tumor necrosis6q23 factor, alpha-inducedNM_006290; protein ENST00000237289; 3 ENST00000485192; BC041790; BC113871; FJ434418; OTTHUMT00000042414; OTTHUMT00000042415; OTTHUMT00000042416; OTTHUMT00000042417; OTTHUMT00000042418; uc021zfv.1; ENST00000535332; ENST00000535574; ENST00000536070; ENST00000539356; ENST00000544646; uc003qhr.3; uc003qhs.3 CPNE4 -1.73 1.32E-05 0.0505 copine IV 3q22.1 NM_130808; ENST00000429747; ENST00000502818; ENST00000503204; ENST00000511604; ENST00000512055; ENST00000512332; AF465771; AK128117; AK295557; BC014396; BC028613; BC075046; OTTHUMT00000356583; OTTHUMT00000356714; OTTHUMT00000356715; OTTHUMT00000356716; OTTHUMT00000356717; OTTHUMT00000356825; OTTHUMT00000356826; OTTHUMT00000356827; OTTHUMT00000356828; OTTHUMT00000356829; OTTHUMT00000356830; OTTHUMT00000357290; uc003eoj.3; uc003eok.3; uc003eol.3; uc003eom.3; uc011blq.2 LMO7 1.8 1.35E-05 0.0505 LIM domain 7 13q22.2 NM_005358; NM_015842; ENST00000321797; ENST00000341547; ENST00000357063; ENST00000377534; ENST00000465261; ENST00000485987; ENST00000526202; AK055465; AK123459; AK304051; BC036428; FJ711162; OTTHUMT00000045297; OTTHUMT00000045298; OTTHUMT00000045299; OTTHUMT00000045300; OTTHUMT00000045301; OTTHUMT00000045302; OTTHUMT00000045303; OTTHUMT00000045304; OTTHUMT00000045305; OTTHUMT00000045306; uc001vju.1; uc001vjv.3; uc001vjw.1; uc010thv.2; uc010thw.2; uc021rkq.1; uc001vjt.1; uc001vjx.1 AIM1 1.61 1.50E-05 0.0507 absent in melanoma6q21 1 NM_001624; ENST00000369066; ENST00000487681; AK300443; OTTHUMT00000041669; OTTHUMT00000041670; OTTHUMT00000041671; uc003prh.3; ENST00000285105; ENST00000535438; uc003pri.3 WWTR1 1.5 1.50E-05 0.0507 WW domain containing3q23-q24 transcriptionNM_001168278; regulator NM_001168280; 1 NM_015472; ENST00000360632; ENST00000465804; ENST00000467467; ENST00000474080; AJ299431; BC014052; OTTHUMT00000356498; OTTHUMT00000356499; OTTHUMT00000356500; OTTHUMT00000356501; OTTHUMT00000356503; OTTHUMT00000356504; OTTHUMT00000356505; OTTHUMT00000356506; OTTHUMT00000356507; OTTHUMT00000356508; OTTHUMT00000356509; OTTHUMT00000356510; uc003exe.3; uc003exf.3; uc003exh.3; uc021xfm.1 FSTL1; MIR198 1.73 1.91E-05 0.0616 follistatin like 1;3q13.33 microRNA 198NM_007085; NR_029584; ENST00000295633; ENST00000424703; ENST00000485968; AK300356; AK311050; BC000055; OTTHUMT00000355399; OTTHUMT00000355401; OTTHUMT00000355402; OTTHUMT00000355403; OTTHUMT00000355404; OTTHUMT00000355405; OTTHUMT00000355406; OTTHUMT00000355407; OTTHUMT00000355408; OTTHUMT00000355409; uc003eds.3; uc010hrb.2; uc011bjh.2; uc021xcw.1; ENST00000539471 AJUBA 2.21 2.43E-05 0.0717 ajuba LIM protein14q11.2 NM_032876; NM_198086; ENST00000262713; ENST00000361265; ENST00000397388; BC007580; BC034968; OTTHUMT00000071685; OTTHUMT00000257240; uc001why.3; uc001whz.3 MTA2 2.06 2.44E-05 0.0717 metastasis associated11q12-q13.1 1 familyNM_004739; member 2 ENST00000278823; ENST00000524902; ENST00000527204; AK301569; BC053650; uc001ntq.2; uc010rlx.1 LIPI 1.63 2.55E-05 0.0718 lipase, member21q11.2 I NM_198996; ENST00000344577; ENST00000536861; JN387910; JN387911; JN387912; JN387913; JN387914; JN387915; JN387916; OTTHUMT00000157810; OTTHUMT00000259009; uc002yjm.3; uc010gkw.2; uc021whe.1; uc021whf.1; uc021whg.1; uc021whh.1; uc021whi.1; uc021whj.1; ENST00000382981 PCSK2 -2.68 2.71E-05 0.072 proprotein convertase20p11.2 subtilisin/kexinNM_001201528; type 2 NM_001201529; NM_002594; ENST00000262545; ENST00000377899; ENST00000459871; ENST00000536609; BC005815; BC040546; OTTHUMT00000078120; OTTHUMT00000101859; OTTHUMT00000127138; OTTHUMT00000127139; uc002wpl.3; uc002wpm.3; uc010zrm.2; uc002wpn.3 AMOT; MIR4329 1.64 2.88E-05 0.072 angiomotin; microRNAXq23 4329 NM_001113490; NM_133265; NR_036255; ENST00000304758; ENST00000371958; ENST00000371959; ENST00000371962; ENST00000462114; ENST00000524145; AK301573; BC094712; BC130294; OTTHUMT00000057950; OTTHUMT00000057951; OTTHUMT00000096600; OTTHUMT00000096601; OTTHUMT00000378570; uc004epr.3; uc004eps.3; uc004ept.1; uc011mtc.1; uc022ccu.1; ENST00000432214 CEP19 -1.52 4.34E-05 0.1012 centrosomal protein3q29 19kDa NM_032898; ENST00000399942; ENST00000409690; BC007827; OTTHUMT00000333080; OTTHUMT00000333081; uc011btw.2 TECRP1 1.59 4.59E-05 0.1019 trans-2,3-enoyl-CoA reductaseENST00000444365 pseudogene 1 MARK3 -1.46 4.81E-05 0.1019 MAP/microtubule14q32.32 affinity-regulatingNM_001128918; kinase 3 NM_001128919; NM_001128920; NM_001128921; NM_002376; ENST00000216288; ENST00000303622; ENST00000335102; ENST00000416682; ENST00000429436; ENST00000440884; ENST00000553942; ENST00000561071; AK124459; AK296643; BC024773; DQ368336; M83780; uc001ymw.4; uc001ymx.4; uc001ymy.4; uc001ymz.4; uc001yna.4; uc001ynd.3; uc010awq.3; uc010tyb.2; uc021sef.1; ENST00000411530; AF159295; uc010awp.3 TRIB2 -1.53 4.94E-05 0.1019 tribbles pseudokinase2p24.3 2 NM_021643; NR_027303; ENST00000155926; ENST00000381465; ENST00000405331; ENST00000483034; BC002637; OTTHUMT00000207114; OTTHUMT00000280497; OTTHUMT00000323584; OTTHUMT00000323585; uc002rbv.4; uc010yjp.2 MIR32 -1.63 5.91E-05 0.1173 microRNA 32 9q31.3 NR_029506; ENST00000384965; uc004bdu.1 SLC17A7 -1.64 6.66E-05 0.1285 solute carrier family19q13 17 (vesicularNM_020309; glutamate ENST00000221485; transporter), member AK095659; 7 BC059379; uc002pnp.3; uc002pnq.1; ENST00000543531; uc002pno.3 NFKBIA -1.47 7.43E-05 0.1313 nuclear factor 14q13of kappa light polypeptideNM_020529; gene ENST00000216797; enhancer in B-cells ENST00000557100; inhibitor, alpha ENST00000557140; ENST00000557389; BC002601; BC004983; OTTHUMT00000276683; uc001wtf.4 PRR11 -1.59 7.58E-05 0.1313 proline rich 1117q22 NM_018304; ENST00000262293; BC008669; uc002ixf.2; uc021uar.1 CCNE2 -1.45 7.94E-05 0.134 cyclin E2 8q22.1 NM_057749; ENST00000308108; ENST00000396133; ENST00000520509; ENST00000523476; BC007015; BC020729; OTTHUMT00000379808; OTTHUMT00000379810; OTTHUMT00000379812; OTTHUMT00000379813; OTTHUMT00000379814; OTTHUMT00000379815; OTTHUMT00000379816; uc003yhc.3; uc003yhd.2; ENST00000542725 1.89 9.95E-05 0.1472 ENST00000273411 ADAM23 -1.47 0.0001 0.1472 ADAM metallopeptidase2q33 domainNM_003812; 23 ENST00000264377; ENST00000374415; AK296844; BC132763; BC132765; OTTHUMT00000256431; OTTHUMT00000336801; OTTHUMT00000336802; ENST00000431817; uc002vbq.3; uc010ziv.2 AMOTL2 1.3 0.0001 0.1472 angiomotin like3q21-q22 2 NM_016201; ENST00000249883; ENST00000422605; ENST00000511759; ENST00000513145; ENST00000514516; AK091040; AK223598; AK299270; BC011454; OTTHUMT00000357273; OTTHUMT00000357274; OTTHUMT00000357275; OTTHUMT00000357367; OTTHUMT00000357368; OTTHUMT00000357369; OTTHUMT00000357370; OTTHUMT00000357534; OTTHUMT00000357535; OTTHUMT00000357536; OTTHUMT00000357537; OTTHUMT00000357643; OTTHUMT00000358149; uc003eqe.1; uc003eqf.2; uc003eqg.1; uc003eqh.1 C3 -1.42 0.0001 0.1472 complement component19p13.3-p13.2 3 NM_000064; ENST00000245907; BC150179; OTTHUMT00000317636; OTTHUMT00000317637; OTTHUMT00000317638; OTTHUMT00000317639; OTTHUMT00000317640; OTTHUMT00000317641; OTTHUMT00000317642; OTTHUMT00000317643; OTTHUMT00000317644; OTTHUMT00000317645; OTTHUMT00000317646; OTTHUMT00000317647; OTTHUMT00000317648; uc002mfm.3; ENST00000461598 DNAJC6 -1.43 0.0001 0.1472 DnaJ (Hsp40) homolog,1p31.3 subfamilyNM_014787; C, member ENST00000263441; 6 ENST00000371069; ENST00000395325; ENST00000494710; AK296408; BC051722; BC109279; BC109280; OTTHUMT00000025134; OTTHUMT00000025135; OTTHUMT00000025137; OTTHUMT00000025138; OTTHUMT00000025139; OTTHUMT00000025140; uc001dcc.1; AK123450; ENST00000410692; OTTHUMT00000025136; uc001dcb.1; uc001dcd.1; uc001dce.1; uc010opc.1 ERVK-7 -1.55 0.0001 0.1598 endogenous retrovirus1q22 groupBC041646; K, member uc001flf.2; 7 uc001flf.3 FAM111B -1.58 0.0001 0.1472 family with sequence11q12.1 similarityNM_001142703; 111, member B NM_001142704; NM_198947; ENST00000343597; ENST00000411426; ENST00000529618; BC130513; uc001nnl.3; uc001nnm.3; uc010rko.2; uc021qjn.1 PADI2 -1.54 0.0001 0.1565 peptidyl arginine1p36.13 deiminase, NM_007365;type II ENST00000375481; ENST00000375486; ENST00000466151; AK295783; BC009701; OTTHUMT00000006624; OTTHUMT00000006625; OTTHUMT00000006626; OTTHUMT00000006627; uc001baf.3; uc001bag.1; uc010ocm.2; ENST00000444885 PDCD4; MIR4680 1.44 0.0001 0.1472 programmed cell10q24 death 4 (neoplasticNM_001199492; transformation NM_014456; inhibitor); NM_145341; microRNA NR_039828; 4680 ENST00000280154; ENST00000393104; ENST00000481353; BC026104; BC031049; OTTHUMT00000050361; OTTHUMT00000050362; OTTHUMT00000050363; OTTHUMT00000050364; OTTHUMT00000050365; OTTHUMT00000050366; OTTHUMT00000050367; OTTHUMT00000050368; OTTHUMT00000050369; OTTHUMT00000050370; uc001kzg.3; uc001kzh.3; uc010qre.2; uc021pye.1 SLC25A33 -1.43 0.0001 0.158 solute carrier family1p36.22 25 (pyrimidineNM_032315; nucleotide ENST00000302692; carrier), member BC004991; 33 BC073135; OTTHUMT00000003851; uc001apw.3 B3GALT1 -1.71 0.0001 0.1472 UDP-Gal:betaGlcNAc2q24.3 beta 1,3-galactosyltransferaseNM_020981; ENST00000392690; 1 BC101545; OTTHUMT00000255211; uc002udz.1; uc021vsc.1 VCAM1 1.45 0.0001 0.1472 vascular cell adhesion1p32-p31 moleculeNM_001078; 1 NM_001199834; NM_080682; ENST00000294728; ENST00000347652; ENST00000370115; ENST00000370119; BC017276; BC068490; BC085003; OTTHUMT00000030213; OTTHUMT00000030214; OTTHUMT00000030215; OTTHUMT00000097431; uc001dti.3; uc001dtj.3; uc010ouj.2 2.32 0.0001 0.1472 DQ591781; uc002bse.1; uc002bse.2 1.59 0.0001 0.1472 ENST00000390880 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not CERK certified by-1.34 peer review) is0.0002 the author/funder.0.1899 All rightsceramide reserved. No kinase reuse22q13.31 allowed withoutNM_022766; permission. ENST00000216264; ENST00000471929; BC067255; BC126940; OTTHUMT00000317924; OTTHUMT00000317975; OTTHUMT00000317976; OTTHUMT00000317977; uc003bia.3; uc010hae.3; ENST00000541677 COTL1 -1.58 0.0002 0.1899 coactosin-like F-actin16q24.1 bindingNM_021149; protein 1 ENST00000262428; BC010039; BC010884; BC016702; BC042970; BC053682; OTTHUMT00000269075; uc002fid.3 COL5A2 1.6 0.0002 0.1899 collagen, type 2q14-q32V, alpha 2 NM_000393; ENST00000374866; BC086874; OTTHUMT00000313523; OTTHUMT00000313525; uc002uqk.3; uc010frx.3; ENST00000452536 C1QL1 -1.46 0.0002 0.1932 complement component17q21 1, qNM_006688; subcomponent-like ENST00000253407; 1 BC008798; OTTHUMT00000371119; uc002ihv.3 ELAVL3 -1.5 0.0002 0.1662 ELAV like neuron-specific19p13.2 RNANM_001420; binding protein NM_032281; 3 ENST00000359227; ENST00000438662; BC011875; uc002mrx.1; uc002mry.1 KRT25 -1.39 0.0002 0.1899 keratin 25, type17q21.2 I NM_181534; ENST00000312150; OTTHUMT00000257218; uc002hve.3; ENST00000394042 KLF12 -1.33 0.0002 0.1662 Kruppel-like factor13q22 12 NM_007249; ENST00000377666; ENST00000377669; ENST00000472022; AF113122; AK291397; BC019680; OTTHUMT00000045271; OTTHUMT00000045272; uc001vjf.3; uc001vjg.3; uc010aeq.3; ENST00000342812 LOX 1.61 0.0002 0.1662 lysyl oxidase 5q23.2 NM_001178102; NM_002317; ENST00000231004; ENST00000513319; AK307559; AK307732; AK315873; BC074820; BC074872; BC089436; OTTHUMT00000250887; OTTHUMT00000371232; OTTHUMT00000371233; OTTHUMT00000371235; OTTHUMT00000371236; uc003ksu.3; uc010jcp.3; uc010jcq.3; uc010jcr.3; uc011cwk.2; ENST00000395480; ENST00000543620 MIR4424 -1.45 0.0002 0.1899 microRNA 4424 NR_039622; uc021pfg.1 NUDT11 -1.44 0.0002 0.1932 nudix hydrolaseXp11.22 11 NM_018159; ENST00000375992; BC009942; OTTHUMT00000056579; uc010njt.3 RCN1P2 1.47 0.0002 0.1899 reticulocalbin 1, EF-hand calciumENST00000545120 binding domain pseudogene 2 LOC101929759 -1.41 0.0002 0.1662 uncharacterized LOC101929759ENST00000501104 VIM 1.56 0.0002 0.1637 vimentin 10p13 NM_003380; ENST00000224237; ENST00000485947; ENST00000544301; BC000163; BC030573; BC066956; OTTHUMT00000047015; OTTHUMT00000047016; OTTHUMT00000047017; OTTHUMT00000047018; OTTHUMT00000047019; OTTHUMT00000047020; OTTHUMT00000047021; OTTHUMT00000047022; OTTHUMT00000047023; uc001iou.2; ENST00000545533 VSTM2L -1.38 0.0002 0.1787 V-set and transmembrane20q11.23 domainNM_080607; containing ENST00000373459; 2 like ENST00000373461; BC033818; OTTHUMT00000079133; OTTHUMT00000079134; OTTHUMT00000079135; uc002xhk.4; ENST00000373458 XG; XGY2 -1.6 0.0002 0.1899 Xg blood group;Xp22.33; Xg pseudogene, Yp11.31NM_001141919; Y-linked 2 NM_001141920; NM_175569; NR_003254; ENST00000381174; ENST00000419513; BC100764; BC100765; BC100766; BC100767; OTTHUMT00000055633; OTTHUMT00000377051; OTTHUMT00000377052; OTTHUMT00000377055; OTTHUMT00000377056; uc004cqp.3; uc010ndb.2; uc011mhg.2; ENST00000426774; ENST00000533923 -1.42 0.0002 0.1844 ENST00000527396 CDH20 1.41 0.0003 0.2014 cadherin 20, type18q21.33 2 NM_031891; ENST00000262717; ENST00000536675; ENST00000538374; AK290190; BC101047; OTTHUMT00000256141; uc002lif.2; uc010dps.1 CIT; MIR1178 -1.55 0.0003 0.2174 citron rho-interacting12q24; 12q24.23serine/threonineNM_001206999; kinase; NM_007174; microRNA 1178 NR_031589; ENST00000261833; ENST00000392521; ENST00000408396; ENST00000537607; AB023166; OTTHUMT00000259410; OTTHUMT00000259411; OTTHUMT00000259412; OTTHUMT00000259413; uc001txh.2; uc001txi.2; uc001txj.2; uc021rer.1 CLU 1.43 0.0003 0.2057 clusterin 8p21-p12 NM_001831; NR_038335; NR_045494; ENST00000316403; ENST00000405140; ENST00000523500; BC010514; BC019588; BX648414; OTTHUMT00000219953; OTTHUMT00000376149; OTTHUMT00000376151; OTTHUMT00000376152; OTTHUMT00000376157; OTTHUMT00000376158; OTTHUMT00000376159; OTTHUMT00000376160; OTTHUMT00000376161; OTTHUMT00000376162; OTTHUMT00000376163; OTTHUMT00000376164; OTTHUMT00000376165; OTTHUMT00000376166; OTTHUMT00000376167; OTTHUMT00000376168; uc003xfw.2; uc003xfx.2; uc003xfy.2; uc003xfz.2; ENST00000380446; ENST00000520012; ENST00000546343; ENST00000560366; OTTHUMT00000376155 DDIAS -1.32 0.0003 0.2174 DNA damage-induced11q14.1 apoptosisNM_145018; suppressor ENST00000329143; ENST00000524921; ENST00000525361; ENST00000525388; ENST00000528759; ENST00000533655; ENST00000533750; AK058145; AK297366; AK299581; BC039268; ENST00000430323; uc001ozt.3; uc009yvd.2; uc010rsr.2; uc010rss.2 DOC2B -1.41 0.0003 0.2014 double C2-like 17p13.3domains, betaNM_003585; ENST00000343572; OTTHUMT00000335122; uc010vpx.1 H1F0 1.32 0.0003 0.2014 H1 histone family,22q13.1 member 0NM_005318; ENST00000340857; BC000145; BC029046; OTTHUMT00000319453; uc003aty.3; ENST00000455466 HR -1.36 0.0003 0.2037 hair growth associated8p21.2 NM_005144; NM_018411; ENST00000312841; ENST00000381418; ENST00000518377; AK308839; BC067128; OTTHUMT00000214213; OTTHUMT00000375340; OTTHUMT00000375341; OTTHUMT00000375343; OTTHUMT00000375344; OTTHUMT00000375345; OTTHUMT00000375346; OTTHUMT00000375347; OTTHUMT00000375348; uc003xas.3; uc003xat.3; uc010lts.2 NDUFB5 1.34 0.0003 0.1972 NADH dehydrogenase3q26.33 (ubiquinone)NM_001199957; 1 beta subcomplex, NM_001199958; 5, 16kDa NM_002492; ENST00000259037; ENST00000472629; ENST00000473500; ENST00000493866; BC005271; BC009796; BC017909; BC093071; OTTHUMT00000348937; OTTHUMT00000348938; OTTHUMT00000348939; OTTHUMT00000348940; OTTHUMT00000349075; OTTHUMT00000349076; OTTHUMT00000349077; OTTHUMT00000349078; OTTHUMT00000349079; OTTHUMT00000349080; OTTHUMT00000349081; OTTHUMT00000349082; OTTHUMT00000349083; OTTHUMT00000349084; OTTHUMT00000349086; uc003fkc.3; uc003fkd.3; uc003fke.3; uc021xhu.1 PNRC2 -1.68 0.0003 0.1972 proline-rich nuclear1p36.11 receptorNM_017761; coactivator 2 ENST00000334351; ENST00000374468; ENST00000471915; BC001959; BC078177; BC085018; OTTHUMT00000038946; OTTHUMT00000038947; OTTHUMT00000038948; uc001big.3; uc021oil.1 RAB5A 1.34 0.0003 0.1972 RAB5A, member3p24.3 RAS oncogeneNM_004162; family ENST00000273047; ENST00000422242; AK295992; AK309287; BC001267; BC018288; OTTHUMT00000252137; OTTHUMT00000339743; OTTHUMT00000339744; OTTHUMT00000339746; OTTHUMT00000339748; OTTHUMT00000339749; OTTHUMT00000339829; OTTHUMT00000339830; uc003cbn.3; uc010hey.3; uc011awg.2; OTTHUMT00000339745 ARHGEF6 -1.42 0.0003 0.2057 Rac/Cdc42 guanineXq26.3 nucleotideNM_004840; exchange factor ENST00000250617; 6 ENST00000370620; ENST00000370622; AK294929; AK295709; BC039856; BC043505; OTTHUMT00000058511; OTTHUMT00000058512; OTTHUMT00000058513; uc004fab.3; uc011mwd.2; uc011mwe.2; ENST00000535227; ENST00000535736 TMEM178B -1.55 0.0003 0.2174 transmembrane7q34 protein 178BNM_001195278; uc003vwg.2 UBE2C -1.4 0.0003 0.2037 ubiquitin-conjugating20q13.12 enzymeNM_007019; E2C NM_181799; NM_181800; NM_181801; NM_181802; NM_181803; ENST00000243893; ENST00000335046; ENST00000352551; ENST00000356455; ENST00000372568; ENST00000405520; ENST00000496085; BC007656; BC016292; BC050736; OTTHUMT00000080309; OTTHUMT00000080310; OTTHUMT00000080311; OTTHUMT00000080312; OTTHUMT00000316949; OTTHUMT00000316950; uc002xpl.3; uc002xpm.3; uc002xpn.3; uc002xpo.3; uc002xpp.3; uc002xpq.3 2.5 0.0003 0.2174 ENST00000385251; uc021thm.1 -1.58 0.0003 0.2174 ENST00000384457; uc021vzi.1 -1.58 0.0003 0.2174 BC062753; uc004aas.1 -1.89 0.0003 0.2014 ENST00000390995 1.6 0.0003 0.2037 ENST00000410811 MIR663A 1.45 0.0004 0.2403 microRNA 663a20p11.1 NR_030386; ENST00000385250; uc021wbn.1 PARVA 1.32 0.0004 0.2276 parvin, alpha 11p15.3 NM_018222; ENST00000334956; ENST00000526746; AK022316; AK304444; BC014535; BC016713; uc001mkh.3; uc010rck.1; ENST00000538608; ENST00000539723; ENST00000550549; uc001mki.3 SPARC 1.55 0.0004 0.2254 secreted protein,5q31.3-q32 acidic, cysteine-richNM_003118; (osteonectin) ENST00000231061; ENST00000537849; AK096969; BC004974; BC008011; BC072457; OTTHUMT00000252430; OTTHUMT00000373826; OTTHUMT00000373827; OTTHUMT00000373828; OTTHUMT00000373829; OTTHUMT00000373830; uc003lug.3; uc003lui.3 TOX2 -1.34 0.0004 0.2276 TOX high mobility20q13.12 group box NM_001098796;family member 2 NM_001098797; NM_001098798; NM_032883; ENST00000341197; ENST00000358131; ENST00000372999; ENST00000423191; ENST00000435864; AK298976; uc002xle.4; uc002xlf.4; uc010ggo.3; uc010ggp.3; uc010zwk.2; ENST00000372992; OTTHUMT00000079329; OTTHUMT00000079330; OTTHUMT00000079331; OTTHUMT00000079332 TMEFF1 -1.37 0.0004 0.2388 transmembrane9q31 protein withNM_003692; EGF-like and ENST00000374879;two follistatin-like domains BC035056; 1 OTTHUMT00000053418; uc004baz.2 TTL -1.43 0.0004 0.2276 tubulin tyrosine2q13 ligase NM_153712; ENST00000233336; ENST00000460450; BC036819; OTTHUMT00000254085; OTTHUMT00000330619; OTTHUMT00000330620; OTTHUMT00000330621; uc002thu.3 LOC100294145 -1.38 0.0004 0.2376 uncharacterized LOC100294145NR_037177; NR_037178; uc003oci.2; uc021ywe.1; ENST00000499196 1.61 0.0004 0.2276 ENST00000384315 -1.38 0.0004 0.2182 OTTHUMT00000365465 -1.35 0.0004 0.2403 ENST00000552998 ARRDC3 -1.32 0.0005 0.2448 arrestin domain5q14.3 containing 3NM_020801; ENST00000265138; ENST00000503192; BC015928; BC053619; OTTHUMT00000369763; OTTHUMT00000369764; OTTHUMT00000369766; OTTHUMT00000369767; OTTHUMT00000370470; OTTHUMT00000370472; OTTHUMT00000370474; uc003kjz.2 CALU -1.57 0.0005 0.2403 calumenin 7q32.1 NM_001130674; NM_001199671; NM_001199672; NM_001199673; NM_001199674; NM_001219; ENST00000249364; ENST00000449187; ENST00000479257; ENST00000535011; ENST00000542996; BC013383; HM002613; HM002615; OTTHUMT00000350533; OTTHUMT00000350534; OTTHUMT00000350535; OTTHUMT00000350536; uc003vnq.3; uc003vnr.3; uc003vns.3; uc022ald.1; uc022ale.1; uc022alg.1; uc022ali.1; ENST00000535623; ENST00000537014; ENST00000537667; ENST00000538394; ENST00000538546; HM002614; uc022alf.1; uc022alh.1 IGSF21 -1.67 0.0005 0.2448 immunoglobin1p36.13 superfamily, memberNM_032880; 21 ENST00000251296; ENST00000497331; AK123172; BC007618; OTTHUMT00000006924; OTTHUMT00000006925; OTTHUMT00000006926; OTTHUMT00000006927; uc001bau.2; uc001bav.2 NDFIP1 1.33 0.0005 0.2448 Nedd4 family interacting5q31.3 proteinNM_030571; 1 ENST00000253814; ENST00000509436; AK075495; BC004317; OTTHUMT00000251859; OTTHUMT00000370657; OTTHUMT00000370658; OTTHUMT00000370659; uc003lmi.4; uc003lmj.1; ENST00000313129 PHC3 -1.65 0.0005 0.2403 polyhomeotic 3q26.2homolog 3 (Drosophila)BC131773; uc003fgr.1 RAVER2 -1.46 0.0005 0.2403 ribonucleoprotein,1p31.3 PTB-bindingNM_018211; 2 ENST00000294428; ENST00000371072; AK299228; BC065303; OTTHUMT00000025240; OTTHUMT00000025241; uc001dbs.2; uc001dbt.2; uc010opb.2; ENST00000430964 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not RBM18 certified by1.36 peer review) is0.0005 the author/funder.0.2403 All rightsRNA reserved. binding No reuse motif9q33.2 allowed protein without 18NM_033117; permission. NR_027125; NR_027126; ENST00000417201; ENST00000483428; AK301050; BC008942; OTTHUMT00000053928; OTTHUMT00000053929; OTTHUMT00000053930; uc004blz.2; uc004bma.2; uc010mvy.2; uc011lyp.1 WHSC1 -1.38 0.0005 0.2448 Wolf-Hirschhorn4p16.3 syndrome candidateNM_001042424; 1 NM_007331; NM_133330; NM_133331; NM_133334; NM_133335; ENST00000382888; ENST00000382891; ENST00000382892; ENST00000382895; ENST00000398261; ENST00000420906; ENST00000436793; ENST00000482415; ENST00000503128; ENST00000508803; ENST00000514045; AF083389; AF083390; AF330040; AK289697; AY694128; BC020545; BC052254; BC141815; BC144464; BC152412; OTTHUMT00000241630; OTTHUMT00000241631; OTTHUMT00000250868; OTTHUMT00000250869; OTTHUMT00000366219; OTTHUMT00000366268; OTTHUMT00000366269; OTTHUMT00000366270; OTTHUMT00000366278; OTTHUMT00000366357; OTTHUMT00000366358; OTTHUMT00000366405; OTTHUMT00000366406; OTTHUMT00000366407; OTTHUMT00000366408; OTTHUMT00000366409; OTTHUMT00000366410; OTTHUMT00000366411; OTTHUMT00000366412; OTTHUMT00000366413; OTTHUMT00000366414; OTTHUMT00000366415; OTTHUMT00000366416; uc003gdx.3; uc003gdy.1; uc003gdz.4; uc003gea.1; uc003geb.4; uc003gec.4; uc003ged.4; uc003gee.4; uc003gef.4; uc003geg.1; uc003geh.1; uc003gei.4; uc010icd.1; uc010ice.1; uc010icf.3; uc011bvh.2 -1.45 0.0005 0.2448 ENST00000446847; OTTHUMT00000099334 AGA 1.44 0.0006 0.2448 aspartylglucosaminidase4q34.3 NM_000027; NM_001171988; NR_033655; ENST00000264595; ENST00000506853; BC012392; OTTHUMT00000361916; OTTHUMT00000361917; OTTHUMT00000361918; OTTHUMT00000361919; OTTHUMT00000361920; OTTHUMT00000361921; uc003iuu.2; uc003iuv.2; uc003iuw.3; S53390; uc010irt.2 CTSK -1.32 0.0006 0.2448 cathepsin K 1q21 NM_000396; ENST00000271651; ENST00000480670; AY429530; BC016058; OTTHUMT00000084732; OTTHUMT00000084733; OTTHUMT00000095841; uc001evp.2; uc009wma.2 CNTNAP2 -1.39 0.0006 0.2448 contactin associated7q35 protein-likeNM_014141; 2 ENST00000361727; ENST00000463592; BC093780; CR933671; OTTHUMT00000327668; OTTHUMT00000327669; OTTHUMT00000327670; uc003weu.2; uc003wev.2; ENST00000538075 IRS1 -1.37 0.0006 0.2448 insulin receptor2q36 substrate 1 NM_005544; ENST00000305123; ENST00000498335; BC053895; OTTHUMT00000256886; OTTHUMT00000258138; uc002voh.4; uc021vxn.1 MIR199A2; MIR214; DNM3OS1.52 0.0006 0.2448 microRNA 199a-2;1q24.3 microRNANR_029618; 214; DNM3 oppositeNR_029627; strand/antisense NR_038397; ENST00000385214; RNA ENST00000385289; ENST00000417354; OTTHUMT00000098131; uc021pev.1 MIR573 -1.72 0.0006 0.2448 microRNA 5734p15.2 NR_030299; ENST00000384964; uc021xmx.1 PRSS35 -1.31 0.0006 0.2448 protease, serine6q14.2 35 NM_001170423; NM_153362; ENST00000369700; BC037170; OTTHUMT00000041352; uc003pjz.3; uc010kbm.3; ENST00000536636; uc021zce.1 RFXAP -1.34 0.0006 0.2448 regulatory factor13q14 X-associatedNM_000538; protein ENST00000255476; ENST00000472888; BC026088; OTTHUMT00000044521; OTTHUMT00000044522; uc001uvu.1 RFK -1.33 0.0006 0.2448 riboflavin kinase9q21.13 NM_018339; ENST00000376736; ENST00000479197; BC007069; OTTHUMT00000052720; OTTHUMT00000052721; OTTHUMT00000356692; OTTHUMT00000356693; OTTHUMT00000356694; OTTHUMT00000356695; uc004akd.2 sep-03 -1.47 0.0006 0.2448 septin 3 22q13.2 NM_019106; NM_145733; ENST00000396425; ENST00000396426; ENST00000406029; AF285108; AK299919; BC111779; OTTHUMT00000075382; OTTHUMT00000257773; OTTHUMT00000322051; OTTHUMT00000322052; OTTHUMT00000322053; OTTHUMT00000322054; uc003bbr.4; uc003bbs.4; uc010gys.3; uc011apj.2; ENST00000291236; ENST00000328414 SLC7A11 2.07 0.0006 0.2448 solute carrier family4q28.3 7 (anionicNM_014331; amino acid ENST00000280612;transporter light chain, BC012087; xc- system), OTTHUMT00000257251; member 11 OTTHUMT00000364387; uc021xrw.1 SULF2 -1.4 0.0006 0.2448 sulfatase 2 20q13.12 NM_001161841; NM_018837; NM_198596; ENST00000359930; ENST00000467815; ENST00000478766; ENST00000484875; AK308829; BC073790; BC110539; OTTHUMT00000079606; OTTHUMT00000079607; OTTHUMT00000079608; OTTHUMT00000079609; OTTHUMT00000079610; OTTHUMT00000354276; OTTHUMT00000354277; OTTHUMT00000354279; OTTHUMT00000354280; OTTHUMT00000354282; OTTHUMT00000354283; OTTHUMT00000356466; uc002xto.3; uc002xtq.3; uc002xtr.3; uc010ghv.1; uc010zyd.2; ENST00000361612; ENST00000371978 TMEM255A -1.83 0.0006 0.2448 transmembraneXq24 protein 255ANM_001104544; NM_001104545; NM_017938; ENST00000309720; ENST00000371352; ENST00000371369; ENST00000440464; ENST00000480821; BC047054; OTTHUMT00000058091; OTTHUMT00000058092; OTTHUMT00000058093; OTTHUMT00000058094; OTTHUMT00000378541; uc004eso.4; uc004esp.4; uc010nqo.3 -1.32 0.0006 0.2448 ENST00000416509; OTTHUMT00000329029 -1.31 0.0006 0.2448 ENST00000516072 -1.53 0.0006 0.2448 ENST00000362515 BMP6 -1.37 0.0007 0.2448 bone morphogenetic6p24-p23 proteinNM_001718; 6 ENST00000283147; OTTHUMT00000039794; uc003mxu.4; ENST00000537240; ENST00000540959 ITGAV 1.55 0.0007 0.2448 integrin alpha V2q31-q32 NM_001144999; NM_001145000; NM_002210; ENST00000261023; ENST00000374907; ENST00000433736; ENST00000474571; BC126231; BC136442; BC144100; OTTHUMT00000255882; OTTHUMT00000334603; OTTHUMT00000334604; OTTHUMT00000334605; OTTHUMT00000334606; OTTHUMT00000334607; OTTHUMT00000334608; OTTHUMT00000334611; ENST00000544640; uc002upq.3; uc010frs.3; uc010zfv.2 LATS2 1.35 0.0007 0.2448 large tumor suppressor13q12.11 kinaseNM_014572; 2 ENST00000382592; AK314235; OTTHUMT00000044102; OTTHUMT00000044104; uc001unr.4; uc009zzs.3; ENST00000496544; ENST00000542899; OTTHUMT00000044103 LRRC4B -1.59 0.0007 0.2448 leucine rich repeat19q13.33 containingNM_001080457; 4B ENST00000389201; uc002pss.3; ENST00000535879 LSM11 -1.37 0.0007 0.2448 LSM11, U7 small5q33.3 nuclear RNANM_173491; associated ENST00000286307; AK023159; BC126449; OTTHUMT00000252580; uc003lxe.1; uc003lxf.1 SCARA3 -1.49 0.0007 0.2448 scavenger receptor8p21 class A, memberNM_016240; 3 NM_182826; ENST00000301904; ENST00000337221; BC060811; BC075067; OTTHUMT00000376258; OTTHUMT00000376259; uc003xga.1; uc003xgb.1 USP31 -1.3 0.0007 0.2448 ubiquitin specific16p12.2 peptidase 31NM_020718; ENST00000219689; AK126447; BX648357; OTTHUMT00000211607; uc002dll.3; uc010bxm.3; uc010vca.2; ENST00000381162; uc002dlk.3 1.49 0.0007 0.2448 ENST00000384109 1.33 0.0007 0.2448 ENST00000544015 ASAP2 -1.49 0.0008 0.2448 ArfGAP with SH32p25|2p24 domain, ankyrinNM_001135191; repeat and PH NM_003887; domain 2 ENST00000281419; ENST00000315273; ENST00000491413; BC063308; OTTHUMT00000237522; OTTHUMT00000353417; OTTHUMT00000353418; OTTHUMT00000353419; uc002qzh.2; uc002qzi.2 CCDC6 1.79 0.0008 0.2448 coiled-coil domain10q21 containingNM_005436; 6 ENST00000263102; BC036757; BC064391; OTTHUMT00000048176; OTTHUMT00000048177; OTTHUMT00000379561; uc001jks.4 IWS1 -1.41 0.0008 0.2448 IWS1 homolog2q14.3 (S. cerevisiae)BC022892; uc002too.1 LYSMD3 -1.42 0.0008 0.2448 LysM, putative5q14.3 peptidoglycan-binding,NM_198273; domain ENST00000315948; containing 3 ENST00000500869; ENST00000509384; BC058027; BC136740; BC136741; CR933624; OTTHUMT00000369986; OTTHUMT00000369987; OTTHUMT00000369989; OTTHUMT00000369990; uc003kjr.3; uc003kjs.1; uc010jaz.2; ENST00000554351 RAB13 -1.42 0.0008 0.2448 RAB13, member1q21.2 RAS oncogeneNM_002870; family ENST00000368575; ENST00000462680; AK128675; BC000799; BC073168; OTTHUMT00000088992; OTTHUMT00000088993; OTTHUMT00000088994; OTTHUMT00000088995; uc001fdt.1; uc001fdu.1 RBBP8; MIR4741 -1.47 0.0008 0.2448 retinoblastoma18q11.2 binding proteinNM_002894; 8; microRNA NM_203291; 4741 NM_203292; NR_039895; ENST00000327155; ENST00000360790; ENST00000399721; ENST00000399722; ENST00000399725; BC001170; BC030590; OTTHUMT00000254699; OTTHUMT00000254700; uc002ktw.3; uc002ktx.1; uc002kty.3; uc002ktz.3; uc002kua.3; uc021uid.1; uc010xap.2 STRBP -1.42 0.0008 0.2448 spermatid perinuclear9q33.3 RNA bindingNM_001171137; protein NM_018387; NR_033234; ENST00000348403; ENST00000360998; ENST00000447404; AK027890; BC017732; uc004bns.3; uc004bnt.3; uc004bnu.3; uc004bnv.3; OTTHUMT00000053982; OTTHUMT00000053983; OTTHUMT00000053984; OTTHUMT00000053985; OTTHUMT00000053986; OTTHUMT00000053988 SNCA -1.36 0.0008 0.2448 synuclein alpha4q21 NM_000345; NM_001146054; NM_001146055; NM_007308; ENST00000336904; ENST00000345009; ENST00000394986; ENST00000394989; ENST00000394991; ENST00000420646; ENST00000502987; ENST00000505199; ENST00000506244; ENST00000508895; BC013293; BC108275; HQ830269; L36674; OTTHUMT00000253547; OTTHUMT00000253548; OTTHUMT00000253549; OTTHUMT00000361318; OTTHUMT00000361319; OTTHUMT00000361320; OTTHUMT00000361321; OTTHUMT00000361322; OTTHUMT00000361323; uc003hso.3; uc003hsp.3; uc003hsq.3; uc003hsr.3; uc021xqc.1; uc010ikt.3 TRERF1 -1.39 0.0008 0.2448 transcriptional6p21.1-p12.1 regulating factorNM_033502; 1 ENST00000340840; ENST00000354325; ENST00000372917; ENST00000372922; ENST00000541110; AJ277275; AJ277276; AK308473; AM404182; OTTHUMT00000040551; OTTHUMT00000040552; OTTHUMT00000040553; uc003osb.2; uc003osc.2; uc003osd.2; uc003ose.2; uc010jxu.1; uc011duq.1 LOC105375732 1.32 0.0008 0.2448 uncharacterized LOC105375732ENST00000518922; OTTHUMT00000381151 ZNF43 -1.41 0.0008 0.2448 zinc finger protein19p13.1-p12 43 NM_003423; ENST00000354959; AK291353; BC006528; CR933640; M61869; OTTHUMT00000250380; X59244; ENST00000397148; uc002nqj.3; uc002nqk.3; uc002nql.3; uc002nqm.3; uc010ecv.3 -1.33 0.0008 0.2448 ENST00000391316 1.57 0.0008 0.2448 DQ594390; uc003asp.2; uc003asp.3 1.35 0.0008 0.2448 ENST00000427398; OTTHUMT00000322387 1.31 0.0008 0.2448 ENST00000364518 -1.39 0.0008 0.2448 ENST00000450850; OTTHUMT00000054981 -1.82 0.0008 0.2448 uc021qxt.1 -1.42 0.0008 0.2448 ENST00000517208 CACNA1A -1.3 0.0009 0.2448 calcium channel,19p13 voltage-dependent,NM_000068; P/Q type,NM_001127221; alpha 1A subunit NM_001127222; NM_001174080; NM_023035; ENST00000360228; AF100774; OTTHUMT00000104062; U79666; U79667; uc002mwv.3; uc002mwx.3; uc002mwy.3; uc010dzc.2; uc010dze.2; uc010xnd.2; uc010xne.2; uc021ups.1; ENST00000325084; ENST00000357018; ENST00000418012; uc021upt.1 PCDH18 1.32 0.0009 0.2448 protocadherin 4q3118 NM_019035; ENST00000344876; ENST00000412923; ENST00000507846; ENST00000510305; ENST00000511115; AK297122; AK298607; BC071581; BC093815; BC143361; OTTHUMT00000364614; OTTHUMT00000364615; OTTHUMT00000364616; OTTHUMT00000364618; OTTHUMT00000364619; uc003ihe.4; uc003ihf.4; uc003ihg.4; uc011cgz.2; uc011cha.2 1.64 0.0009 0.2448 DQ587539; uc010tzn.1 1.64 0.0009 0.2448 DQ590589; uc001ytt.2 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by1.64 peer review) is0.0009 the author/funder.0.2448 All rights reserved. No reuse allowed withoutDQ590589; permission. uc021wgt.1 1.64 0.0009 0.2448 DQ590589; uc002yjd.1 1.64 0.0009 0.2448 DQ590589; uc001ejj.2; uc001ejj.3 1.64 0.0009 0.2448 DQ590589; uc021otc.1 1.64 0.0009 0.2448 DQ587539; uc011mfj.1 1.64 0.0009 0.2448 DQ587539; uc011mfk.2 1.64 0.0009 0.2448 DQ587539; uc021wkj.1 1.64 0.0009 0.2448 DQ587539; uc001ejl.1 1.64 0.0009 0.2448 DQ587539; uc021otd.1 1.64 0.0009 0.2448 DQ590589; uc003jaf.2; uc003jaf.3 1.64 0.0009 0.2448 DQ590589; uc002ksy.1 1.64 0.0009 0.2448 DQ587539; uc021vlb.1 1.64 0.0009 0.2448 DQ587539; uc002ksx.1 1.64 0.0009 0.2448 DQ587539; uc021vnx.1 1.64 0.0009 0.2448 DQ587539; uc002tqf.2; uc002tqf.3 1.64 0.0009 0.2448 DQ587539; uc002tqd.2; uc002tqd.3 1.64 0.0009 0.2448 DQ587539; uc010yzq.1 1.64 0.0009 0.2448 DQ590589; uc002tql.2; uc002tql.3 1.64 0.0009 0.2448 DQ590589; uc021vny.1 1.64 0.0009 0.2448 DQ587539; uc004awy.2; uc004awy.3 1.64 0.0009 0.2448 DQ590589; uc022bks.1 1.64 0.0009 0.2448 DQ587539; uc003ztd.1 1.64 0.0009 0.2448 DQ587539; uc004abe.1; uc004abe.2 1.64 0.0009 0.2448 DQ590589; uc004fsq.1; uc004fsq.2 -1.79 0.0009 0.2448 DQ595616; uc011dsj.1 1.64 0.0009 0.2448 DQ587539; uc022bra.1 1.64 0.0009 0.2448 DQ590589; uc003zte.1 1.64 0.0009 0.2448 DQ590589; uc022bgz.1 1.64 0.0009 0.2448 DQ587539; uc021xoh.1 1.64 0.0009 0.2448 DQ587539; uc003gyy.2; uc003gyy.3 1.64 0.0009 0.2448 DQ590589; uc021rmz.1 1.64 0.0009 0.2448 DQ590589; uc021rnf.1 1.64 0.0009 0.2448 DQ590589; uc011bzm.1; uc011bzm.2 1.64 0.0009 0.2448 DQ590589; uc022brq.1 GRK5 -1.38 0.001 0.2462 G protein-coupled10q26.11 receptor kinaseNM_005308; 5 ENST00000369108; ENST00000392870; AK298261; AK309761; BC064506; OTTHUMT00000050652; OTTHUMT00000050653; uc001led.3; uc009xzh.3; uc010qta.1; ENST00000369106; ENST00000457057; ENST00000473264; ENST00000421206; OTTHUMT00000050638; OTTHUMT00000050651 MFSD6 -1.31 0.001 0.252 major facilitator2q32.2 superfamily NM_017694;domain containing ENST00000281416; 6 ENST00000392328; ENST00000489793; AK302647; BC050537; OTTHUMT00000255931; OTTHUMT00000334928; OTTHUMT00000334929; OTTHUMT00000334930; OTTHUMT00000334931; OTTHUMT00000334932; OTTHUMT00000334933; OTTHUMT00000334934; OTTHUMT00000334935; uc002urz.2; uc010zge.1; ENST00000535751; ENST00000542423 NAIP -1.35 0.001 0.2519 NLR family, apoptosis5q13.2 inhibitoryNM_022892; protein AK124511; uc003jyj.1 PDIA4 -1.44 0.001 0.2563 protein disulfide7q35 isomerase familyNM_004911; A, member ENST00000286091; 4 BC000425; BC006344; BC011754; OTTHUMT00000317077; OTTHUMT00000317078; OTTHUMT00000317079; uc003wff.2 TSPAN6 1.33 0.001 0.2484 tetraspanin 6 Xq22 NM_003270; ENST00000373020; ENST00000496771; AK309581; BC012389; OTTHUMT00000057483; OTTHUMT00000057484; OTTHUMT00000057485; uc004ega.1; uc010nna.1; ENST00000431386 TMEM30A 1.37 0.001 0.2559 transmembrane6q14.1 protein 30ANM_001143958; NM_018247; ENST00000230461; ENST00000370050; ENST00000475111; BC009006; OTTHUMT00000041247; OTTHUMT00000041248; OTTHUMT00000375188; OTTHUMT00000375189; uc003phw.2; uc003phx.2; ENST00000545449 ENOPH1 -1.46 0.0011 0.2662 enolase-phosphatase4q21.22 1 NM_021204; ENST00000273920; ENST00000509635; BC001317; BC065815; OTTHUMT00000252638; OTTHUMT00000363376; OTTHUMT00000363377; uc003hmv.3; ENST00000456931; uc003hmx.3 LMNB1 1.4 0.0011 0.2572 lamin B1 5q23.2 NM_001198557; NM_005573; ENST00000261366; ENST00000395354; ENST00000460265; BC012295; BC052951; BC103723; OTTHUMT00000250956; OTTHUMT00000259188; OTTHUMT00000259189; OTTHUMT00000259190; OTTHUMT00000259191; OTTHUMT00000259193; OTTHUMT00000371422; OTTHUMT00000371423; uc003kud.2; uc010jdb.2; uc011cxb.2; OTTHUMT00000259194; OTTHUMT00000372431 NFE2L3 -1.37 0.0011 0.2572 nuclear factor,7p15.2 erythroid 2-likeNM_004289; 3 ENST00000056233; BC068455; OTTHUMT00000214088; uc003sxq.3; ENST00000398175 1.32 0.0011 0.2572 ENST00000516692; uc021pko.1 OXCT1 -1.31 0.0012 0.2731 3-oxoacid CoA-transferase5p13.1 1 NM_000436; ENST00000196371; ENST00000509987; ENST00000510634; ENST00000512084; ENST00000513081; AK298352; AK315902; BC009001; OTTHUMT00000211594; OTTHUMT00000367149; OTTHUMT00000367150; OTTHUMT00000367151; OTTHUMT00000367152; OTTHUMT00000367153; OTTHUMT00000367154; OTTHUMT00000367155; uc003jmn.3; uc011cpo.2; uc011cpp.2; ENST00000546045 CDKN3 -1.36 0.0012 0.2726 cyclin-dependent14q22 kinase inhibitorNM_001130851; 3 NM_005192; ENST00000335183; ENST00000395577; ENST00000442975; ENST00000458126; ENST00000541304; ENST00000543789; ENST00000556102; ENST00000556305; AF213034; AY257475; BC064965; OTTHUMT00000276893; uc001xap.3; uc001xar.3; uc010aoi.1; uc010aoj.2; ENST00000434252; ENST00000439312 GPHN -1.3 0.0012 0.2731 gephyrin 14q23.3 NM_001024218; NM_020806; ENST00000315266; ENST00000459628; ENST00000478722; ENST00000543237; ENST00000544752; AK025169; AK294532; AK295577; AK297447; BC030016; OTTHUMT00000074298; OTTHUMT00000074299; OTTHUMT00000286408; uc001xiw.3; uc001xix.3; uc001xiy.3; uc010tss.2; uc010tst.2; uc010tsu.2 PNMA2 -1.31 0.0012 0.2731 paraneoplastic8p21.2 Ma antigen 2NM_007257; ENST00000522362; ENST00000522764; BC036489; BC047515; BC062301; OTTHUMT00000375709; OTTHUMT00000375711; OTTHUMT00000375712; OTTHUMT00000375713; OTTHUMT00000375714; OTTHUMT00000376203; OTTHUMT00000376236; OTTHUMT00000376237; uc003xez.2; OTTHUMT00000375710; uc022atc.1 PIEZO2 -1.5 0.0012 0.2731 piezo-type mechanosensitive18p11.22 NM_022068; ion channel componentENST00000302079; 2 ENST00000383408; ENST00000503781; ENST00000538948; AK095053; OTTHUMT00000254528; uc002kos.2; uc002kot.1; ENST00000285141; AK098782; uc002koq.3; uc002kou.2; uc002kov.1; uc002kov.2; uc002kow.1 PRKCB -1.4 0.0012 0.2692 protein kinase 16p11.2C, beta NM_002738; NM_212535; ENST00000303531; ENST00000321728; ENST00000487674; BC036472; OTTHUMT00000254504; OTTHUMT00000254505; OTTHUMT00000268350; OTTHUMT00000268351; OTTHUMT00000268352; OTTHUMT00000268353; OTTHUMT00000268354; OTTHUMT00000268355; OTTHUMT00000268356; OTTHUMT00000268357; uc002dmd.3; uc002dme.3 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not SNORD42A certified by1.45 peer review) is0.0012 the author/funder.0.2713 All rightssmall reserved. nucleolar No reuse17q11 RNA, allowed C/D without boxNR_000014; permission.42A ENST00000459584; uc002hcm.1 SLC24A3 -1.77 0.0012 0.2702 solute carrier family20p13 24 (sodium/potassium/calciumNM_020689; ENST00000328041; exchanger), OTTHUMT00000078207; member 3 uc002wrl.3 TUBE1 1.48 0.0012 0.2702 tubulin, epsilon6q21 1 NM_016262; ENST00000368657; ENST00000368662; BC025405; BC031101; OTTHUMT00000041867; OTTHUMT00000041868; OTTHUMT00000041869; uc003pvq.3; ENST00000368658 1.81 0.0012 0.2704 DQ595407; uc021sve.1 1.35 0.0012 0.2687 DQ591120; uc002kph.2; uc002kph.3 -1.43 0.0013 0.2851 ENST00000408088 CDC25B -1.46 0.0014 0.2877 cell division cycle20p13 25B NM_004358; NM_021872; NM_021873; ENST00000245960; ENST00000340833; ENST00000344256; ENST00000379598; ENST00000439880; ENST00000467519; AK295573; AK299028; AK299192; BC006395; BC009953; BC051711; BX640836; BX647988; FR695900; FR695901; OTTHUMT00000077776; OTTHUMT00000077777; OTTHUMT00000077778; OTTHUMT00000077779; OTTHUMT00000077780; OTTHUMT00000077781; OTTHUMT00000077782; uc002wjl.3; uc002wjm.3; uc002wjn.3; uc002wjo.3; uc002wjp.3; uc002wjq.3; uc010zqk.2; uc010zql.2; uc010zqm.2; uc021waa.1 HLA-B -1.45 0.0014 0.2877 major histocompatibility6p21.3 complex,NM_005514; class I, B AK124160; AK309345; AK310586; BC013187; BC091497; M64259; OTTHUMT00000076924; OTTHUMT00000314806; OTTHUMT00000314807; OTTHUMT00000314808; OTTHUMT00000314809; OTTHUMT00000314810; OTTHUMT00000314811; OTTHUMT00000314812; uc011fcp.1; uc011fcq.1; uc011fct.1; GQ141863; uc011fcr.1; uc011fcs.1; uc021zkx.1 TCF19 -1.38 0.0014 0.2854 transcription factor6p21.3 19 NM_001077511; NM_007109; BC002493; BC033086; BC044632; OTTHUMT00000077326; OTTHUMT00000077327; OTTHUMT00000314779; uc011fbu.2; uc011fbv.2 TCF19 -1.4 0.0014 0.2877 transcription factor6p21.3 19 NM_001077511; NM_007109; BC002493; BC033086; BC044632; OTTHUMT00000310721; OTTHUMT00000310722; OTTHUMT00000310723; uc011gag.2; uc011gah.2 LOC100294145 -1.4 0.0014 0.2877 uncharacterized LOC100294145NR_037177; NR_037178; uc011fon.2; uc021zmi.1; uc011fon.1 ACSL1 -1.32 0.0015 0.2877 acyl-CoA synthetase4q35.1 long-chainNM_001995; family member ENST00000281455; 1 ENST00000454703; ENST00000504342; ENST00000504900; ENST00000507295; ENST00000513317; ENST00000515030; AK096117; AK296550; AK296826; AK303486; BC050073; DQ083028; OTTHUMT00000361098; OTTHUMT00000361099; OTTHUMT00000361100; OTTHUMT00000361101; OTTHUMT00000361102; OTTHUMT00000361103; OTTHUMT00000361108; OTTHUMT00000361109; OTTHUMT00000361110; OTTHUMT00000361111; OTTHUMT00000361112; uc003iws.1; uc003iwt.1; uc003iwu.1; uc003iww.2; uc010ise.1; uc011ckm.1; uc011ckn.1; ENST00000437665; ENST00000509038; OTTHUMT00000361113 ALK -1.68 0.0015 0.2877 anaplastic lymphoma2p23 receptorNM_004304; tyrosine kinase ENST00000389048; ENST00000431873; ENST00000498037; OTTHUMT00000324994; OTTHUMT00000324995; OTTHUMT00000324996; uc002rmy.3; AB374365; uc010ymo.2 MIR1265 1.54 0.0015 0.2877 microRNA 1265 NR_031668; ENST00000408444; uc021pne.1 MAP1A -1.48 0.0015 0.2877 microtubule associated15q15.3 proteinNM_002373; 1A ENST00000300231; ENST00000382031; OTTHUMT00000132894; OTTHUMT00000132895; uc001zrt.3; ENST00000399453; ENST00000442025 TCF19 -1.36 0.0015 0.2877 transcription factor6p21.3 19 NM_001077511; NM_007109; BC002493; BC033086; BC044632; OTTHUMT00000314223; OTTHUMT00000314224; OTTHUMT00000314225; uc011imf.2; uc011img.2 TCF19 -1.36 0.0015 0.2877 transcription factor6p21.3 19 NM_001077511; NM_007109; BC002493; BC033086; BC044632; OTTHUMT00000088012; OTTHUMT00000258048; OTTHUMT00000315311; uc011jhp.2; uc011jhq.2 LOC401127 -1.4 0.0015 0.2877 WD repeat domain4p14 5 pseudogeneNR_026854; uc011byn.2; ENST00000513652; uc011byn.1 -1.56 0.0015 0.2921 ENST00000537921 C16orf72 -1.83 0.0016 0.2934 chromosome 1616p13.2 open readingAK057657; frame 72 uc002czn.2; uc002czn.3 MAD2L1 -1.33 0.0016 0.2937 MAD2 mitotic 4q27arrest deficient-likeNM_002358; 1 (yeast) ENST00000296509; AF394735; BC000356; BC005945; BC070283; OTTHUMT00000256525; OTTHUMT00000364557; OTTHUMT00000364558; OTTHUMT00000364559; OTTHUMT00000364560; uc003idl.2; uc003idm.2 SPIN2A 1.33 0.0016 0.2934 spindlin family,Xp11.1 member 2A NM_019003; ENST00000374906; ENST00000374908; BC071694; OTTHUMT00000058915; OTTHUMT00000058916; uc004dvb.3; uc022bxx.1 -1.39 0.0016 0.2969 DQ579694; uc011ltq.1 3.28 0.0016 0.2949 ENST00000458976 CYFIP2 -1.54 0.0017 0.3032 cytoplasmic FMR15q33.3 interactingNM_001037332; protein 2 NM_001037333; NM_014376; ENST00000435847; ENST00000520960; ENST00000521420; ENST00000522463; AK294220; AK295865; AK303702; BC011762; OTTHUMT00000373710; OTTHUMT00000373711; OTTHUMT00000373712; OTTHUMT00000373713; OTTHUMT00000373715; OTTHUMT00000373716; OTTHUMT00000373717; OTTHUMT00000373720; OTTHUMT00000373796; OTTHUMT00000373797; OTTHUMT00000373798; OTTHUMT00000373799; OTTHUMT00000373800; OTTHUMT00000373801; OTTHUMT00000373802; OTTHUMT00000373803; OTTHUMT00000373804; OTTHUMT00000373805; OTTHUMT00000373806; OTTHUMT00000373807; OTTHUMT00000373808; OTTHUMT00000373809; OTTHUMT00000373810; OTTHUMT00000373811; uc011ddn.2; uc011ddo.2; uc011ddp.2; uc021ygm.1; uc021ygn.1; uc021ygo.1; ENST00000318218; ENST00000347377; ENST00000377576; OTTHUMT00000373718; ENST00000541131; uc003lwt.3 NEB 1.38 0.0017 0.3036 nebulin 2q22 NM_001164507; NM_001164508; NM_004543; ENST00000172853; ENST00000397345; ENST00000409198; ENST00000427231; ENST00000498015; AK300079; AK300674; AK300722; BC050436; BC063136; BX648963; OTTHUMT00000332406; OTTHUMT00000333620; OTTHUMT00000333621; OTTHUMT00000333622; OTTHUMT00000333624; OTTHUMT00000333650; OTTHUMT00000333651; OTTHUMT00000333652; OTTHUMT00000333753; OTTHUMT00000333754; OTTHUMT00000333755; OTTHUMT00000333756; OTTHUMT00000338133; OTTHUMT00000338177; U35637; uc002txq.3; uc002txr.3; uc002txt.4; uc002txu.3; uc010fnx.3; uc010fny.2; uc010zbz.2; uc010zca.2; uc010zcb.2; uc021vrc.1; uc021vrd.1; X83957; ENST00000397336; ENST00000397342; ENST00000439291; ENST00000509223; ENST00000536533; OTTHUMT00000333623; uc021vrb.1 -1.41 0.0017 0.3067 ENST00000410395 -1.52 0.0017 0.3036 DQ592954; uc003orh.1 1.39 0.0017 0.303 DQ601324; uc021yxx.1 -1.35 0.0017 0.3029 ENST00000408500; uc021rtv.1 DNER -1.71 0.0018 0.3084 delta/notch like2q36.3 EGF repeat containingNM_139072; ENST00000341772; ENST00000482831; AK304631; BC035009; OTTHUMT00000331902; OTTHUMT00000331903; uc002vpv.3; uc010zly.1; ENST00000543700 TNC -1.33 0.0018 0.3137 tenascin C 9q33 NM_002160; ENST00000341037; ENST00000350763; ENST00000423613; ENST00000481475; ENST00000535648; ENST00000537320; ENST00000542877; BC151843; GU473235; OTTHUMT00000055418; OTTHUMT00000055419; OTTHUMT00000055420; OTTHUMT00000055421; OTTHUMT00000055422; OTTHUMT00000055423; uc004bjj.4; uc010mvf.3; uc022bmj.1; ENST00000340094; ENST00000345230; ENST00000346706; ENST00000442945 1.33 0.0018 0.3113 ENST00000547554 MIR548X -2.2 0.0019 0.3172 microRNA 548x NR_036166; uc021tct.1 RNF182 -1.42 0.0019 0.3138 ring finger protein6p23 182 NM_001165032; NM_001165033; NM_001165034; NM_152737; ENST00000488300; ENST00000537388; ENST00000537663; ENST00000544682; BC030666; BC050030; OTTHUMT00000039911; OTTHUMT00000039912; OTTHUMT00000039913; OTTHUMT00000356080; OTTHUMT00000356081; uc003nbe.3; uc003nbf.3; uc003nbg.3; uc021ylw.1; uc021ylx.1; uc021yly.1 -1.95 0.0019 0.3137 AX747167; uc003xqy.1 ELOVL2 -1.44 0.002 0.3215 ELOVL fatty acid6p24.2 elongase 2 NM_017770; ENST00000354666; BC050278; BC060809; OTTHUMT00000039849; uc003mzp.4 PPP2R1B -1.39 0.002 0.3215 protein phosphatase11q23.2 2, regulatoryNM_001177562; subunit A, beta NM_001177563; NM_002716; NM_181699; NM_181700; ENST00000311129; ENST00000341980; ENST00000393055; ENST00000426998; ENST00000527614; ENST00000530787; AK293388; BC027596; EF491803; EF491816; uc001plw.1; uc001plx.1; uc009yye.1; uc009yyf.1; uc010rwi.1; uc010rwj.1; uc010rwk.1; uc010rwl.1; ENST00000412902; ENST00000427203 -1.34 0.002 0.3215 ENST00000561392 -1.58 0.002 0.3215 ENST00000516039 -1.34 0.002 0.3215 ENST00000542270 1.32 0.002 0.3215 DQ601943; uc022bar.1 GCH1 -1.4 0.0021 0.3258 GTP cyclohydrolase14q22.1-q22.2 1 NM_000161; NM_001024024; NM_001024070; NM_001024071; ENST00000254299; ENST00000395514; ENST00000491895; ENST00000536224; ENST00000543643; AY137465; BC025415; OTTHUMT00000074213; OTTHUMT00000074214; OTTHUMT00000074215; OTTHUMT00000276895; S43856; uc001xbh.1; uc001xbi.1; uc001xbj.1; uc001xbk.1; uc001xbl.1; uc010aol.1; ENST00000395524 LINC00920 -1.34 0.0021 0.3279 long intergenic non-protein codingAK056683; RNA 920ENST00000499966; uc002eoo.1 NUDT19 -1.46 0.0021 0.3261 nudix hydrolase19q13.11 19 NM_001105570; ENST00000397061; uc010edf.3 TENM2 1.37 0.0021 0.3258 teneurin transmembrane5q34 proteinNM_001122679; 2 ENST00000403607; ENST00000518659; ENST00000518693; ENST00000519204; ENST00000520394; ENST00000545108; AB032953; AK056053; BX648178; HE578283; OTTHUMT00000371066; OTTHUMT00000371190; OTTHUMT00000371191; OTTHUMT00000371192; OTTHUMT00000371193; OTTHUMT00000371194; OTTHUMT00000371195; OTTHUMT00000376096; OTTHUMT00000376097; uc003lzt.4; uc010jjd.3; uc010jje.3; uc021yhi.1; uc003lzq.2; uc003lzr.4 ZC3H12C -1.34 0.0021 0.3258 zinc finger CCCH-type11q22.3 containingNM_033390; 12C ENST00000278590; ENST00000453089; ENST00000528673; AB096241; AK095101; AK299100; uc001pkq.2; uc001pkr.4; uc009yxw.3; uc010rwd.2; uc010rwc.2 1.37 0.0021 0.3261 ENST00000509548; OTTHUMT00000362851 RP11-91H12.2 -1.44 0.0021 0.3266 OTTHUMT00000371985; ENST00000502813 CENPQ 1.31 0.0022 0.3298 centromere protein6p12.3 Q NM_018132; ENST00000335783; BC016279; OTTHUMT00000040855; uc003ozh.1 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not KIF23 certified by-1.34 peer review) is0.0022 the author/funder.0.3283 All rightskinesin reserved. family No reuse member15q23 allowed without23 NM_004856; permission. NM_138555; ENST00000260363; ENST00000352331; ENST00000395392; ENST00000558303; ENST00000558585; ENST00000559279; ENST00000560125; ENST00000561089; AK303874; AK308322; AK310402; BC051826; uc002asb.3; uc002asc.3; uc010bih.2; uc010bii.3; uc010ukc.2; ENST00000537891 MIR877 -1.39 0.0022 0.3283 microRNA 8776p21.33 NR_030615; uc021yud.1; ENST00000401282 MIR877 -1.39 0.0022 0.3283 microRNA 8776p21.33 NR_030615; uc021zkn.1 MIR877 -1.39 0.0022 0.3283 microRNA 8776p21.33 NR_030615; uc021zna.1 MIR877 -1.39 0.0022 0.3283 microRNA 8776p21.33 NR_030615; uc021zou.1 MIR877 -1.39 0.0022 0.3283 microRNA 8776p21.33 NR_030615; uc021zre.1 MIR877 -1.39 0.0022 0.3283 microRNA 8776p21.33 NR_030615; uc021zto.1 MIR877 -1.39 0.0022 0.3283 microRNA 8776p21.33 NR_030615; uc021zvz.1 PYGB -1.32 0.0022 0.3283 phosphorylase,20p11.21 glycogen; brainNM_002862; ENST00000216962; ENST00000471359; BC017045; BC030795; OTTHUMT00000078415; OTTHUMT00000078416; OTTHUMT00000078417; uc002wup.3 1.44 0.0022 0.3283 DQ591574; uc021suv.1 CNN2 1.77 0.0023 0.3343 calponin 2 19p13.3 NM_004368; NM_201277; ENST00000263097; ENST00000348419; AK293171; AK300788; AY927510; AY927514; BC141818; BC148264; uc002lqt.1; uc002lqu.3; uc002lqv.3; uc010drz.1; uc010xgb.2; uc010xgc.2; ENST00000442531 SCARNA12 1.56 0.0023 0.3343 small Cajal body-specific12p13.31 RNANR_003010; 12 ENST00000459155; uc001qsg.3 TRPM8 -1.32 0.0023 0.3343 transient receptor2q37.1 potential cationNM_024080; channel, ENST00000324695; subfamily M, member ENST00000355722; 8 ENST00000409625; ENST00000433712; ENST00000466594; AY532375; BC001135; BC033137; BC126342; OTTHUMT00000131005; OTTHUMT00000131006; OTTHUMT00000131007; OTTHUMT00000131008; OTTHUMT00000131009; OTTHUMT00000131010; OTTHUMT00000216806; OTTHUMT00000277115; OTTHUMT00000277116; OTTHUMT00000277117; OTTHUMT00000329816; OTTHUMT00000329817; OTTHUMT00000329818; uc002vvh.3; uc002vvi.3; uc002vvj.3; uc010fyj.3; uc010fyk.3 CDK19 -1.31 0.0024 0.3343 cyclin-dependent6q21 kinase 19 NM_015076; ENST00000323817; ENST00000368911; ENST00000413605; ENST00000497709; AK300567; BC024247; BC037289; OTTHUMT00000041804; OTTHUMT00000041805; OTTHUMT00000041806; OTTHUMT00000041807; OTTHUMT00000041808; OTTHUMT00000041809; OTTHUMT00000041810; uc003puh.1; uc003pui.1; uc011eax.1; ENST00000392576 MIR548AN -1.45 0.0024 0.3343 microRNA 548an NR_039765; uc021rly.1 PNRC2 -1.58 0.0024 0.3345 proline-rich nuclear1p36.11 receptorNM_017761; coactivator 2 AF374386; BC001959; BC078177; BC085018; uc002qvo.3 SYNE2 -1.42 0.0024 0.3362 spectrin repeat14q23.2 containing, nuclearNM_015180; envelope NM_182910; 2 NM_182913; NM_182914; ENST00000341472; ENST00000344113; ENST00000357395; ENST00000358025; ENST00000394768; ENST00000441438; ENST00000458046; ENST00000553455; ENST00000554584; ENST00000554805; ENST00000555002; ENST00000555022; AF357236; AK074055; AK127612; AK128631; AK297874; AY061759; AY184205; AY927627; BC036941; BC071873; BX537642; BX538095; CR749324; OTTHUMT00000276994; uc001xgk.3; uc001xgl.3; uc001xgm.3; uc001xgn.3; uc001xgo.3; uc001xgp.3; uc001xgq.3; uc001xgr.3; uc001xgs.3; uc001xgt.3; uc010apw.1; uc010apx.1; uc010apy.3; uc010apz.1; uc010aqa.3; uc010tsi.2; uc021ruh.1; uc021rui.1; ENST00000261678; ENST00000356081 STAU2 -1.32 0.0024 0.3362 staufen double-stranded8q21.11 RNANM_001164380; binding protein 2NM_001164381; NM_001164382; NM_001164383; NM_001164384; NM_001164385; NM_014393; ENST00000355780; ENST00000517542; ENST00000519961; ENST00000521210; ENST00000521419; ENST00000521451; ENST00000521727; ENST00000522509; ENST00000522695; ENST00000522962; ENST00000523558; ENST00000524104; ENST00000524300; AK307841; AL079285; BC008369; BC008370; BC110447; BC110448; CR627442; uc003xzm.3; uc003xzn.3; uc003xzo.3; uc003xzp.3; uc003xzq.3; uc003xzr.3; uc003xzs.3; uc010lzk.3; uc010lzl.1; uc011lfg.2; uc011lfh.2; uc011lfi.2 TOMM20 -1.38 0.0024 0.3362 translocase of 1q42outer mitochondrialNM_014765; membrane ENST00000366607; 20 homolog (yeast) ENST00000467767; BC000882; BC066335; BC071994; BC100286; BC107851; OTTHUMT00000095551; OTTHUMT00000095552; OTTHUMT00000095553; uc001hwl.3 YME1L1 -1.41 0.0024 0.3362 YME1-like 1 ATPase10p14 GQ179994; ENST00000390428; L02827; uc001wbt.1; uc021rpd.1 ZFP69 -1.3 0.0024 0.3362 ZFP69 zinc finger1p34.2 protein NM_198494; ENST00000372705; ENST00000372706; ENST00000482712; BC041873; BC144174; OTTHUMT00000019082; OTTHUMT00000019083; OTTHUMT00000019084; uc001cfo.3; uc009vwb.3; uc010ojk.2 1.33 0.0024 0.3345 DQ593611; uc011drs.1; uc011drs.2 HMSD -1.39 0.0025 0.3364 histocompatibility18q22.1 (minor) serpinNM_001123366; domain containing ENST00000408945; ENST00000526932; OTTHUMT00000134010; OTTHUMT00000280624; uc010dqj.3 TMEM132B -1.48 0.0025 0.3364 transmembrane12q24.31 protein 132BNM_052907; ENST00000299308; ENST00000418253; ENST00000535886; AB058689; AK094786; BC113366; BC113368; BC131621; uc001uhe.1; uc001uhf.1; uc021rgl.1; uc021rgm.1 LOC100294145 -1.32 0.0025 0.3364 uncharacterized LOC100294145NR_037177; NR_037178; uc011gkw.2; uc021zog.1; uc011gkw.1 LOC100294145 -1.38 0.0025 0.3364 uncharacterized LOC100294145NR_037177; NR_037178; uc011hfg.2; uc021zqn.1; uc011hfg.1 LOC100294145 -1.38 0.0025 0.3364 uncharacterized LOC100294145NR_037177; NR_037178; uc011ixz.2; uc021zvf.1; uc011ixz.1 ZNF638-IT1 -1.44 0.0025 0.3364 ZNF638 intronic2p13.1 transcript 1 OTTHUMT00000327430; ENST00000434786 2.13 0.0025 0.3364 DQ583379; uc021uhb.1 1.77 0.0025 0.3364 DQ578031; uc022bjg.1 1.77 0.0025 0.3364 DQ587746; uc004apx.1 LOXHD1 -1.44 0.0026 0.3379 lipoxygenase homology18q21.1 domainsNM_001145472; 1 NM_001145473; NM_001173129; NM_144612; ENST00000300591; ENST00000335730; ENST00000398686; ENST00000398705; ENST00000536111; ENST00000536736; AK127869; AK302484; AK302848; BC041860; BX647229; OTTHUMT00000255893; OTTHUMT00000255894; OTTHUMT00000317346; OTTHUMT00000317347; OTTHUMT00000317348; OTTHUMT00000317349; OTTHUMT00000317350; OTTHUMT00000317351; uc002lcd.4; uc002lce.4; uc002lcf.4; uc002lcg.1; uc010xcu.1; uc010xcv.2; uc010xcw.1; uc010xcx.1; ENST00000441893 PALM3 -1.33 0.0026 0.3365 paralemmin 3 19p13.12 NM_001145028; ENST00000340790; uc010xnk.1 SLC7A5 1.52 0.0026 0.3365 solute carrier family16q24.3 7 (aminoNM_003486; acid transporter ENST00000261622; light chain, L system), BC039692; member BC042600; 5 OTTHUMT00000269110; uc002fkm.3 -1.51 0.0026 0.3379 AK055601; uc002wbj.3 EFNA3 -1.48 0.0027 0.34 ephrin-A3 1q21-q22 NM_004952; ENST00000368408; ENST00000498667; AK316248; BC017722; BC110406; OTTHUMT00000085429; OTTHUMT00000085430; OTTHUMT00000085431; uc001fhf.3; uc010pex.2; ENST00000418360 EIF1AX-AS1 -1.45 0.0028 0.3464 EIF1AX antisenseXp22.12 RNA 1 ENST00000424026; OTTHUMT00000056005 MN1 -1.39 0.0028 0.3475 meningioma (disrupted22q12.1 in balancedNM_002430; translocation) ENST00000302326; 1 ENST00000497225; AK307152; OTTHUMT00000320737; OTTHUMT00000320738; OTTHUMT00000320739; uc003adj.3; uc010gvg.3 TCF19 -1.42 0.0029 0.3534 transcription factor6p21.3 19 NM_001077511; NM_007109; BC002493; BC033086; BC044632; OTTHUMT00000311683; OTTHUMT00000311684; OTTHUMT00000311685; uc011gwh.2; uc011gwi.2 TCF19 -1.42 0.0029 0.3534 transcription factor6p21.3 19 NM_001077511; NM_007109; BC002493; BC033086; BC044632; OTTHUMT00000312779; OTTHUMT00000312780; OTTHUMT00000312781; uc011hos.2; uc011hot.2 1.43 0.0029 0.3496 DQ574810; uc022bux.1 1.43 0.0029 0.3496 DQ574810; uc022bfx.1 -1.34 0.0029 0.3496 ENST00000516372 1.37 0.0029 0.3521 ENST00000506305; OTTHUMT00000365544 C8orf4 -1.36 0.003 0.3566 chromosome 88p11.2 open readingNM_020130; frame 4 ENST00000315792; BC020623; BC021672; OTTHUMT00000376943; uc003xnq.2 SCARNA2 1.37 0.003 0.3566 small Cajal body-specific1q13.1 RNANR_003023; 2 ENST00000458748; uc001dwo.1 -1.46 0.003 0.3544 ENST00000515904 CTGF 1.44 0.0031 0.3595 connective tissue6q23.1 growth factorNM_001901; ENST00000367976; BC087839; OTTHUMT00000042239; uc003qcz.3 DPYSL3 -1.34 0.0031 0.3595 dihydropyrimidinase-like5q32 3 NM_001197294; NM_001387; ENST00000343218; ENST00000398514; ENST00000504965; BC039006; BC077077; OTTHUMT00000373421; OTTHUMT00000373422; OTTHUMT00000373423; OTTHUMT00000373424; OTTHUMT00000373425; OTTHUMT00000373426; OTTHUMT00000377410; OTTHUMT00000377411; OTTHUMT00000377412; uc003lon.1; uc003loo.3; ENST00000534907 RNF152 -1.65 0.0031 0.3595 ring finger protein18q21.33 152 NM_173557; ENST00000312828; BC094004; BC111956; OTTHUMT00000256180; uc002lih.1; uc021ula.1 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by-1.4 peer review) is0.0031 the author/funder.0.3594 All rights reserved. No reuse allowed withoutENST00000366185; permission. OTTHUMT00000056728 -1.36 0.0031 0.3595 ENST00000514134; OTTHUMT00000366137 MIR4324 -1.44 0.0032 0.3635 microRNA 4324 NR_036209; uc021uxj.1 1.3 0.0032 0.3635 DQ573684; uc021wke.1 1.3 0.0032 0.3635 DQ583165; uc010zbc.1; uc010zbc.2 ADNP2 -1.46 0.0033 0.3635 ADNP homeobox18q23 2 NM_014913; ENST00000262198; ENST00000560561; BC071589; uc002lnw.3 CD83 -1.55 0.0033 0.3635 CD83 molecule6p23 NM_001040280; NM_001251901; NM_004233; ENST00000379153; BC030830; OTTHUMT00000039916; uc003nbh.3; uc003nbi.3; uc021ylz.1 KIF11 -1.37 0.0033 0.3635 kinesin family member10q24.1 11 NM_004523; ENST00000260731; BC126211; BC136474; OTTHUMT00000049401; uc001kic.3 MKI67 -1.43 0.0033 0.3635 marker of proliferation10q26.2 Ki-67NM_001145966; NM_002417; ENST00000368653; ENST00000368654; ENST00000484853; AJ567756; AJ567757; OTTHUMT00000050999; OTTHUMT00000051000; OTTHUMT00000051001; OTTHUMT00000051002; OTTHUMT00000051003; uc001lke.3; uc001lkf.3; uc009yav.1; uc009yaw.1; ENST00000368652; ENST00000537609; ENST00000538447 MIR3145 1.75 0.0033 0.3635 microRNA 3145 NR_036099; uc021zfw.1 MIR4307 1.48 0.0033 0.3635 microRNA 4307 NR_036193; uc021rrs.1 TRIM53AP 1.37 0.0033 0.3635 tripartite motif11q14.3 containing 53A,NR_028346; pseudogene uc010rtz.2 TULP4 -1.38 0.0033 0.3635 tubby like protein6q25-q26 4 ENST00000432358; OTTHUMT00000042868 -1.32 0.0033 0.3635 -2.38 0.0033 0.3635 DQ601842; uc021xyf.1 RAET1K 1.53 0.0034 0.3643 retinoic acid early6q25.1 transcript 1KNR_024045; pseudogene ENST00000533735; uc003qnq.3; uc003qnq.2 1.48 0.0034 0.3643 DQ578824; uc010uhq.1; uc010uhq.2 -1.47 0.0034 0.3643 AK125301; uc004ebq.1 1.5 0.0034 0.3643 ENST00000364912; 7SK 1.64 0.0034 0.3636 uc021xto.1 1.44 0.0034 0.3643 ENST00000500632 2.48 0.0034 0.3643 DQ582894; uc021qgp.1 ATP1A3 -1.34 0.0035 0.3658 ATPase, Na+/K+19q13.31 transporting,NM_001256213; alpha 3 polypeptide NM_001256214; NM_152296; ENST00000302102; ENST00000543770; ENST00000545399; AK295833; AK296557; AK316069; BC009282; BC013763; OTTHUMT00000268107; OTTHUMT00000268108; OTTHUMT00000268109; OTTHUMT00000268111; OTTHUMT00000268112; OTTHUMT00000268113; OTTHUMT00000268114; OTTHUMT00000268115; uc010xwf.2; uc010xwg.2; ENST00000368080; ENST00000473840; ENST00000535899; OTTHUMT00000268110; uc002osg.3; uc002osh.3; uc010xwh.2 HLA-B -1.42 0.0035 0.3659 major histocompatibility6p21.3 complex,NM_005514; class I, B ENST00000412585; AK124160; AK309345; AK310586; BC013187; BC091497; M64259; OTTHUMT00000076280; OTTHUMT00000258071; OTTHUMT00000258072; OTTHUMT00000258074; OTTHUMT00000258076; OTTHUMT00000258077; OTTHUMT00000335177; uc003ntg.1; uc003nth.2; uc010jso.2; ENST00000428231; ENST00000452596; GQ141863; OTTHUMT00000258073; uc003nti.1; uc010jsn.1; uc021yum.1 RNF24 -1.3 0.0035 0.3658 ring finger protein20p13 24 NM_001134337; NM_001134338; NM_007219; ENST00000336095; ENST00000358395; ENST00000432261; ENST00000545616; BC000213; BC039584; uc002wkh.2; uc002wki.2; uc002wkj.2; OTTHUMT00000077795; OTTHUMT00000252862 1.3 0.0035 0.3643 ENST00000448256; OTTHUMT00000347397 1.41 0.0035 0.3665 uc001lsr.1 DPCR1 1.48 0.0036 0.3713 diffuse panbronchiolitis6p21.33 criticalNM_080870; region 1 OTTHUMT00000311924; uc011hoc.1 MIR663B 1.39 0.0036 0.3713 microRNA 663b NR_031608; ENST00000408361; uc021vpu.1 TRIB1 -1.41 0.0037 0.3727 tribbles pseudokinase8q24.13 1 NM_025195; ENST00000311922; ENST00000519576; ENST00000520847; ENST00000521778; AK022787; AK297539; AK307561; BC063292; OTTHUMT00000381430; OTTHUMT00000381431; OTTHUMT00000381432; OTTHUMT00000381433; uc003yrx.3; uc010mdn.3; uc011lis.2; uc022bay.1 1.64 0.0037 0.3727 DQ581539; uc002nbx.2 -1.53 0.0037 0.3727 ENST00000408094 -1.32 0.0037 0.3727 uc021yox.1 MIR3688-1 -1.4 0.0038 0.3731 microRNA 3688-1 NR_037459; uc021xtt.1 NLGN4Y; NLGN4X -1.48 0.0038 0.3727 neuroligin 4, Y-linked;Yq11.221; neuroligin Xp22.33NM_001206850; 4, X-linked NM_020742; NM_181332; ENST00000275857; ENST00000381092; ENST00000381093; ENST00000381095; ENST00000469740; ENST00000538097; AK055471; AK291036; AY358562; BC034018; OTTHUMT00000055670; OTTHUMT00000055671; OTTHUMT00000055672; OTTHUMT00000055673; OTTHUMT00000055674; OTTHUMT00000055675; uc004crp.3; uc004crq.3; uc004crr.3; uc010ndh.3; uc010ndi.3; uc010ndj.3 MGC24103 -1.64 0.0038 0.3731 uncharacterized9p22.3 MGC24103 BC020879 -1.35 0.0038 0.3731 ENST00000408835 -1.31 0.0038 0.3731 ENST00000447643; OTTHUMT00000339263; uc003tjg.1 -1.3 0.0038 0.3731 uc022akl.1 CDKN2C -1.42 0.0039 0.3764 cyclin-dependent1p32 kinase inhibitorNM_001262; 2C (p18, NM_078626;inhibits CDK4) ENST00000262662; ENST00000371761; ENST00000396148; BC000598; BC005041; BC016173; OTTHUMT00000022057; OTTHUMT00000022058; uc001csf.3; uc001csg.3 -1.34 0.0039 0.3764 ENST00000401198; uc021wbe.1 1.36 0.0039 0.3764 ENST00000438582; OTTHUMT00000052925 -1.37 0.0039 0.3764 ENST00000527543 DOCK10 -1.44 0.004 0.3794 dedicator of cytokinesis2q36.2 10 NM_014689; ENST00000258390; ENST00000409592; ENST00000474102; AK293847; AK293879; EU236710; OTTHUMT00000331158; OTTHUMT00000331159; OTTHUMT00000331231; OTTHUMT00000331232; OTTHUMT00000331233; OTTHUMT00000331234; OTTHUMT00000331235; OTTHUMT00000331236; OTTHUMT00000331237; OTTHUMT00000331238; OTTHUMT00000331246; uc002voa.2; uc002vob.2; uc002voc.2; uc010fwz.1; ENST00000373702; OTTHUMT00000331230; uc002vod.1 HAP1 -1.59 0.004 0.3794 huntingtin-associated17q21.2-q21.3 proteinNM_001079870; 1 NM_001079871; NM_177977; ENST00000310778; ENST00000341193; ENST00000347901; ENST00000393939; OTTHUMT00000257418; OTTHUMT00000257419; OTTHUMT00000257420; OTTHUMT00000257421; OTTHUMT00000257422; uc002hxm.1; uc002hxn.1; uc002hxo.1; uc002hxp.1 1.46 0.004 0.3788 ENST00000556013 2.15 0.004 0.3794 DQ595071; uc001nbf.2 ANKRD13C -1.35 0.0041 0.3794 ankyrin repeat1p31.1 domain 13C NM_030816; ENST00000262346; ENST00000370944; ENST00000464236; AL136717; BC028840; OTTHUMT00000025903; OTTHUMT00000025904; OTTHUMT00000025905; OTTHUMT00000025906; OTTHUMT00000092212; uc001dex.4; uc009wbk.3; BC042365; uc001dey.4 RNF213 -1.34 0.0041 0.3813 ring finger protein17q25.3 213 NM_001256071; NM_020954; ENST00000319921; ENST00000427003; ENST00000508628; AB046838; AB537889; AL161961; BC036891; BC040341; OTTHUMT00000364861; uc002jyg.1; ENST00000336301; ENST00000456466; uc002jyf.3; uc002jyh.2; uc010dhx.2; uc021uen.1 SIPA1L1 -1.56 0.0041 0.3794 signal-induced14q24.2 proliferation-associatedNM_015556; 1 like ENST00000358550; 1 ENST00000381232; ENST00000537413; ENST00000554874; ENST00000555818; AF090989; AK094532; AK122930; AK302650; BC146777; CR936651; uc001xmr.1; uc001xms.3; uc001xmt.3; uc001xmu.3; uc010ttm.2; uc001xmv.3; uc021rvu.1 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not CEP170P1 certified by-1.37 peer review) is0.0042 the author/funder.0.3824 All rightscentrosomal reserved. No reuse protein4q26 allowed 170kDa without NR_003135; pseudogenepermission. ENST00000412784;1 uc003icb.3 FLRT1 -1.33 0.0042 0.3836 fibronectin leucine11q13.1 rich transmembraneNM_013280; protein ENST00000246841; 1 BC018370; uc001nyi.1; uc021qks.1 GFRA2 -1.65 0.0042 0.3836 GDNF family receptor8p21.3 alpha 2NM_001165038; NM_001165039; NM_001495; ENST00000517328; ENST00000518077; ENST00000520676; ENST00000524240; BC041688; OTTHUMT00000376253; OTTHUMT00000376254; OTTHUMT00000376255; OTTHUMT00000376335; OTTHUMT00000376336; OTTHUMT00000376337; OTTHUMT00000376338; OTTHUMT00000378764; uc003wzu.1; uc003wzv.1; uc003wzw.1; ENST00000400782; OTTHUMT00000378763 MIR3115 -1.61 0.0042 0.3834 microRNA 3115 NR_036057; uc021oid.1 SNORD114-4 1.62 0.0042 0.3836 small nucleolar14q32 RNA, C/D boxNR_003196; 114-4 uc001yiu.3; ENST00000363962; uc001yiu.2 LOC90784 -1.4 0.0042 0.382 uncharacterized2p11.2 LOC90784 NR_026984; uc010yta.1 -1.53 0.0042 0.382 ENST00000412798; OTTHUMT00000320951 1.32 0.0042 0.3823 ENST00000517043; uc022bad.1 -1.49 0.0042 0.3823 ENST00000363656 CACNG4 -1.31 0.0043 0.3854 calcium channel,17q24 voltage-dependent,NM_014405; gamma ENST00000262138; subunit 4 BC034532; uc002jft.2; ENST00000375684 FAM84B -1.32 0.0043 0.3855 family with sequence8q24.21 similarityNM_174911; 84, member ENST00000304916; B ENST00000517458; BC052957; OTTHUMT00000381487; OTTHUMT00000381488; uc003yrz.2; uc022bbc.1 NAV1 -1.55 0.0044 0.3866 neuron navigator1q32.3 1 NM_001167738; NM_020443; ENST00000367295; ENST00000367296; ENST00000367302; ENST00000469130; AB033039; AK056158; BC069250; OTTHUMT00000087013; OTTHUMT00000087014; OTTHUMT00000087015; OTTHUMT00000087016; OTTHUMT00000087017; OTTHUMT00000087018; OTTHUMT00000087019; OTTHUMT00000097758; OTTHUMT00000331155; uc001gwu.3; uc001gwv.1; uc001gww.2; uc001gwx.3; uc001gwy.1; ENST00000295624; ENST00000367297; ENST00000367300; ENST00000367301; ENST00000391966; uc021phi.1 SDK1 -1.46 0.0044 0.3865 sidekick cell adhesion7p22.2 moleculeNM_001079653; 1 NM_152744; ENST00000389531; ENST00000404826; ENST00000466611; AK055987; AK074083; OTTHUMT00000323702; OTTHUMT00000323703; OTTHUMT00000323704; OTTHUMT00000323705; OTTHUMT00000323706; OTTHUMT00000323707; OTTHUMT00000323708; OTTHUMT00000323709; OTTHUMT00000323710; uc003smx.3; uc003smy.3; uc003smz.3; uc010kso.3; NR_027816; ENST00000446104 1.33 0.0044 0.3865 ENST00000457224; OTTHUMT00000078369 -1.41 0.0044 0.3865 ENST00000459621 1.34 0.0044 0.3865 uc003gsx.4 LUM 1.43 0.0045 0.3866 lumican 12q21.33 NM_002345; ENST00000266718; ENST00000548071; BC007038; BC035997; uc001tbm.3 MIR2113 1.47 0.0045 0.3866 microRNA 2113 NR_031579; ENST00000459007; uc021zdb.1 RHNO1 -1.42 0.0045 0.3866 RAD9-HUS1-RAD112p13.33 interactingNM_001252499; nuclear orphan 1NM_001252500; NR_027365; ENST00000461997; ENST00000464682; ENST00000489288; OTTHUMT00000351286; OTTHUMT00000351287; OTTHUMT00000351288; uc001qlh.3; uc001qli.3; uc010see.2 SLITRK6 1.45 0.0045 0.3866 SLIT and NTRK-like13q31.1 family, memberNM_032229; 6 ENST00000400286; BC101070; BC101071; OTTHUMT00000045404; uc001vll.1; uc021rla.1 1.41 0.0045 0.3866 ENST00000420172; OTTHUMT00000321888 LOC100130964 1.45 0.0046 0.3872 ADAM metallopeptidase8p11.22 domainENST00000519537; 3A-like ENST00000523523; OTTHUMT00000376913; OTTHUMT00000376914 CDS1 -1.37 0.0046 0.3872 CDP-diacylglycerol4q21.23 synthase 1NM_001263; ENST00000295887; AY312584; BC074833; BC074881; OTTHUMT00000252817; OTTHUMT00000363041; uc011ccv.2; uc010ike.1 DGKD -1.39 0.0046 0.3872 diacylglycerol kinase,2q37.1 delta 130kDaNM_003648; NM_152879; ENST00000264057; ENST00000409813; ENST00000442524; ENST00000489613; AK311044; BC032102; OTTHUMT00000257072; OTTHUMT00000317152; OTTHUMT00000317153; OTTHUMT00000317154; OTTHUMT00000317155; OTTHUMT00000317156; OTTHUMT00000317157; OTTHUMT00000317158; OTTHUMT00000317159; OTTHUMT00000330085; OTTHUMT00000330086; OTTHUMT00000330087; OTTHUMT00000330088; uc002vui.1; uc002vuj.1; uc010fyh.1; uc010fyi.1; BC036826; OTTHUMT00000317151; uc002vuk.1 -1.54 0.0046 0.3866 ENST00000408110 ANXA2P3 1.41 0.0047 0.3909 annexin A2 pseudogene10q21.3 3 NR_001446; uc009xpm.1 SNORD114-6 1.57 0.0047 0.3908 small nucleolar14q32 RNA, C/D boxNR_003198; 114-6 ENST00000364393; uc001yiw.3; uc001yiw.2 1.31 0.0047 0.3908 ENST00000451090; OTTHUMT00000023100 -1.43 0.0047 0.3905 DQ597779; uc021ptx.1 -1.32 0.0047 0.3908 ENST00000539313 BTG2 -1.32 0.0049 0.3946 BTG family, member1q32 2 NM_006763; ENST00000290551; BC105948; BC105949; OTTHUMT00000087168; OTTHUMT00000087169; uc001gzq.3 C15orf65 -1.59 0.0049 0.3946 chromosome 1515q21.3 open readingNM_001198784; frame 65 uc002ada.3 FN1 -1.57 0.0049 0.3944 fibronectin 1 2q34 NM_002026; NM_054034; NM_212474; NM_212476; NM_212478; NM_212482; ENST00000323926; ENST00000336916; ENST00000354785; ENST00000356005; ENST00000357867; ENST00000359671; ENST00000421182; ENST00000426059; ENST00000432072; ENST00000443816; ENST00000446046; ENST00000490833; AJ320525; AJ320526; AJ320527; AK300246; BC117176; BC143754; BX537590; BX641150; CR749316; EF550133; EF550135; OTTHUMT00000256667; OTTHUMT00000256668; OTTHUMT00000256669; OTTHUMT00000256670; OTTHUMT00000337226; OTTHUMT00000337228; OTTHUMT00000337229; OTTHUMT00000337230; OTTHUMT00000337231; OTTHUMT00000337232; OTTHUMT00000337233; OTTHUMT00000337234; OTTHUMT00000337235; OTTHUMT00000337238; OTTHUMT00000337239; OTTHUMT00000337240; OTTHUMT00000337242; OTTHUMT00000337243; OTTHUMT00000337244; OTTHUMT00000337246; OTTHUMT00000337247; OTTHUMT00000337248; OTTHUMT00000337323; OTTHUMT00000337326; OTTHUMT00000337327; OTTHUMT00000341268; uc002vez.3; uc002vfa.3; uc002vfc.3; uc002vfe.3; uc002vff.3; uc002vfg.3; uc002vfh.3; uc002vfi.3; uc002vfj.3; uc002vfk.1; uc00 -1.7 0.0049 0.3946 ENST00000410374 -1.4 0.0049 0.3946 ENST00000364481 LGR5 -1.31 0.005 0.3995 leucine-rich repeat12q22-q23 containingNM_003667; G protein-coupled ENST00000266674; receptor 5 ENST00000536515; ENST00000540815; AK075399; BC096324; BC096325; BC096326; FN820440; ENST00000451585; uc001swl.3; uc001swm.3; uc001swn.1; uc021rar.1 PTPN1 -1.32 0.005 0.3979 protein tyrosine20q13.1-q13.2 phosphatase,NM_002827; non-receptor ENST00000371621; type 1 ENST00000541713; AK299830; BC015660; BC018164; OTTHUMT00000079694; uc002xvl.3; uc010zys.2 SLC4A4 1.42 0.005 0.3988 solute carrier family4q21 4 (sodiumNM_001098484; bicarbonate cotransporter), NM_001134742; member NM_003759; 4 ENST00000264485; ENST00000340595; ENST00000351898; ENST00000425175; ENST00000512686; ENST00000514331; AF004813; AF069510; AF157492; BC030977; CR749482; OTTHUMT00000252158; OTTHUMT00000362090; OTTHUMT00000362091; OTTHUMT00000362107; OTTHUMT00000362108; uc003hfy.3; uc003hfz.3; uc003hga.2; uc003hgb.3; uc003hgc.4; uc010iib.3; uc010iic.3; uc010iid.3 1.34 0.005 0.3995 ENST00000408632 LUZP6; MTPN -1.43 0.0051 0.3995 leucine zipper 7q33protein 6; myotrophinNM_001128619; NM_145808; ENST00000393085; ENST00000435723; AK309816; BC028093; OTTHUMT00000340921; OTTHUMT00000340922; uc003vte.4; uc010lmv.3 KRCC1 -1.38 0.0051 0.4015 lysine-rich coiled-coil2p11.2 1 NM_016618; ENST00000347055; BC015927; BC107580; OTTHUMT00000252664; uc002sso.1; uc002ssp.1; uc021vko.1 LOC730159 1.41 0.0051 0.3995 uncharacterized1q25.1 LOC730159 NM_001195190; uc021pez.1; ENST00000417563; OTTHUMT00000097581 -1.53 0.0051 0.3995 ENST00000450980; OTTHUMT00000047630 STAT6 -1.41 0.0052 0.4033 signal transducer12q13 and activatorNM_001178078; of transcription NM_001178079; 6, interleukin-4 inducedNM_001178080; NM_001178081; NM_003153; NR_033659; ENST00000300134; ENST00000454075; ENST00000537215; ENST00000538913; ENST00000543873; ENST00000556155; AK308751; BC075852; uc001sna.3; uc009zpe.3; uc009zpf.3; uc009zpg.3; uc010srb.2; uc010src.2; uc010srd.2; ENST00000535201; ENST00000542516; ENST00000542721 1.33 0.0052 0.4033 ENST00000423276; OTTHUMT00000195205 -1.4 0.0052 0.4033 ENST00000418945; DQ599242; OTTHUMT00000041601; uc003ppu.3 MIR4659B -1.54 0.0053 0.4043 microRNA 4659b NR_039807; uc022aqu.1 ZNF138 -1.38 0.0053 0.4033 zinc finger protein7q11.21 138 NM_001160183; NM_006524; ENST00000307355; ENST00000359735; ENST00000430838; ENST00000437743; ENST00000440155; ENST00000440598; ENST00000494380; BC131762; BC141847; OTTHUMT00000344743; OTTHUMT00000344744; OTTHUMT00000344745; OTTHUMT00000344746; OTTHUMT00000344747; OTTHUMT00000344748; NR_027660; NR_027661; ENST00000397136; uc003ttg.3; uc003tth.3; uc010kzs.3; uc011kdp.2; uc011kdq.2 1.35 0.0053 0.4035 ENST00000413255; OTTHUMT00000039991 1.4 0.0053 0.4033 ENST00000459046 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not RASGEF1B certified by-1.3 peer review) is0.0054 the author/funder.0.4058 All rightsRasGEF reserved. domain No reuse4q21.21 family allowed member withoutNM_152545; permission. 1B ENST00000264400; ENST00000335927; ENST00000436139; ENST00000509081; ENST00000514889; AK291459; BC036784; BC121003; BC121004; OTTHUMT00000362830; OTTHUMT00000362831; OTTHUMT00000362832; OTTHUMT00000362833; OTTHUMT00000362834; OTTHUMT00000362835; OTTHUMT00000362844; uc003hmi.1; uc003hmj.1; uc003hmk.3; uc010ijq.1; ENST00000395570 SLC36A4 -1.34 0.0054 0.4051 solute carrier family11q21 36 (proton/aminoAK093898; acid uc001pdl.1 symporter), member 4 VKORC1L1 -1.42 0.0054 0.4043 vitamin K epoxide7q11.21 reductase NM_173517;complex subunit ENST00000360768; 1 like 1 ENST00000434382; AK304077; BC027734; OTTHUMT00000251612; OTTHUMT00000345550; uc003tul.3; uc011kds.2; DQ594001; uc003tum.1 -1.43 0.0055 0.4077 DQ586415; uc021src.1 -1.67 0.0055 0.4077 ENST00000516793 1.38 0.0055 0.4077 DQ574554; uc021swy.1 -1.43 0.0055 0.4077 DQ586415; uc021sri.1 CACNA1G -1.42 0.0056 0.4079 calcium channel,17q22 voltage-dependent,NM_001256324; T type, alpha NM_001256325; 1G subunit NM_001256326; NM_001256327; NM_001256328; NM_001256329; NM_001256330; NM_001256331; NM_001256332; NM_001256333; NM_001256334; NM_001256359; NM_001256360; NM_001256361; NM_018896; NM_198376; NM_198377; NM_198378; NM_198379; NM_198380; NM_198382; NM_198383; NM_198384; NM_198385; NM_198386; NM_198387; NM_198388; NM_198396; NM_198397; NR_046054; NR_046055; NR_046056; NR_046057; NR_046058; ENST00000352832; ENST00000354983; ENST00000358244; ENST00000359106; ENST00000360761; ENST00000416767; ENST00000429973; ENST00000442258; ENST00000502264; ENST00000503485; ENST00000505165; ENST00000507336; ENST00000507510; ENST00000507609; ENST00000507896; ENST00000510115; ENST00000510366; ENST00000512389; ENST00000513689; ENST00000513964; ENST00000514079; ENST00000514181; ENST00000514717; ENST00000515165; ENST00000515411; ENST00000515765; AF029228; BC110995; DQ494457; DQ494460; DQ494461; DQ494463; DQ494467; DQ494470; DQ494471; DQ494472; DQ494473; DQ494474; DQ494476; DQ494479; OTTHUMT00000367762; OTTHUM 2.49 0.0056 0.4079 DQ587169; uc021uhg.1 -1.61 0.0056 0.4079 OTTHUMT00000374887 1.43 0.0057 0.4113 ENST00000363576 1.31 0.0057 0.408 uc022bbr.1 1.34 0.0058 0.4113 ENST00000516449 1.55 0.0058 0.4119 DQ587734; uc010yxb.1 1.55 0.0058 0.4119 DQ574014; uc002tgh.1 -1.57 0.0059 0.413 DQ573673; uc021tys.1 EIF5 -1.37 0.006 0.4155 eukaryotic translation14q32.32 initiationNM_001969; factor 5 NM_183004; ENST00000216554; ENST00000392715; ENST00000558506; ENST00000560200; BC007728; BC032866; BX537367; U49436; uc001ymu.3; uc001ymq.3; uc001ymr.3; uc001ymt.3 MIR766 1.31 0.006 0.4155 microRNA 766Xq24 NR_030413; ENST00000390223; uc022cdl.1 -1.32 0.0061 0.417 ENST00000556738 TRIM49D2; TRIM49D1 1.46 0.0062 0.4196 tripartite motif11q14.3 containing 49D2;NM_001105522; tripartite motif NM_001206627; containing 49D1 uc009yvv.3 -1.52 0.0062 0.4181 ENST00000410597 LINC00940 1.32 0.0063 0.4214 long intergenic non-protein codingNR_036546; RNA 940 ENST00000418006; uc001qjw.3 1.47 0.0063 0.4214 DQ600033; uc021swc.1 MBD3L5 -1.48 0.0064 0.4221 methyl-CpG binding19p13.2 domain proteinNM_001136507; 3-like 5 ENST00000329753; uc010xjl.2; ENST00000450263 -1.5 0.0064 0.4221 DQ581328; uc021wth.1 -1.45 0.0064 0.4225 uc021vpk.1 1.37 0.0065 0.4259 DQ585554; uc002nwq.1 -1.3 0.0065 0.4248 ENST00000458832 1.32 0.0066 0.426 ENST00000534168 PPP3R1 -1.36 0.0067 0.4291 protein phosphatase2p15 3, regulatoryNM_000945; subunit ENST00000234310;B, alpha ENST00000409377; ENST00000409752; BC027913; OTTHUMT00000326765; OTTHUMT00000326786; OTTHUMT00000326787; uc002sei.1 LOC100506730 -1.51 0.0067 0.4291 uncharacterized1p36 LOC100506730NR_037847; uc021ohp.1 2.48 0.0067 0.4302 DQ586005; uc021tth.1 1.6 0.0067 0.4291 ENST00000364788 SOWAHA -1.3 0.0068 0.4304 sosondowah ankyrin5q31.1 repeat domainNM_175873; family ENST00000378693; member A BC104771; OTTHUMT00000133062; uc003kxw.3 1.31 0.0068 0.4304 ENST00000517210; 7SK; uc021xsw.1 1.54 0.0068 0.4304 ENST00000363518 1.37 0.0069 0.4337 ENST00000363336 1.62 0.0069 0.4351 DQ580770; uc011mhy.1; uc011mhy.2 1.62 0.0069 0.4351 DQ580770; uc022bso.1 LINC01031 1.4 0.007 0.4357 long intergenic1q31.2 non-protein codingENST00000420807; RNA 1031 OTTHUMT00000086758 SNORD56B -1.88 0.0071 0.4394 small nucleolar14q24.2 RNA, C/D boxNR_001276; 56B ENST00000384713; uc001xmq.3; uc001xmq.2 1.3 0.0071 0.4381 uc021tbj.1 1.32 0.0071 0.4392 ENST00000411386; uc021vrx.1 HLA-B -1.45 0.0072 0.4429 major histocompatibility6p21.3 complex,NM_005514; class I, B AK124160; AK309345; AK310586; BC013187; BC091497; M64259; OTTHUMT00000311963; OTTHUMT00000311964; OTTHUMT00000311965; OTTHUMT00000311966; OTTHUMT00000311967; OTTHUMT00000311968; OTTHUMT00000311969; OTTHUMT00000311970; uc011hpo.2; uc011hpp.2; uc011hps.1; GQ141863; uc011hpq.1; uc011hpr.1; uc021zrp.1 MIR335 1.38 0.0072 0.4429 microRNA 3357q32.2 NR_029899; ENST00000362173; uc011kpi.2; uc011kpi.1 1.35 0.0072 0.4415 ENST00000441746; OTTHUMT00000328345 -1.36 0.0072 0.4429 ENST00000516103 -1.46 0.0072 0.4433 ENST00000543596 1.36 0.0072 0.4426 ENST00000408572 ANKRD52 -1.52 0.0073 0.4434 ankyrin repeat12q13.3 domain 52 NM_173595; ENST00000267116; ENST00000548241; BC042070; uc001skm.4; ENST00000417002; AK098479; uc001skn.1; uc021qza.1 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by-1.71 peer review) is0.0073 the author/funder.0.4434 All rights reserved. No reuse allowed withoutDQ593990; permission. uc003ofv.2; uc003ofv.3 KRTAP21-1 1.45 0.0074 0.4466 keratin associated21q22.1 protein 21-1NM_181619; ENST00000335093; BC105029; BC105031; OTTHUMT00000128229; uc011adi.2 -1.38 0.0074 0.4445 uc021wsq.1 -1.49 0.0074 0.4457 ENST00000464659; OTTHUMT00000355354 -1.46 0.0074 0.4457 BC069792; uc001jtm.3 DPYSL5 -1.43 0.0075 0.447 dihydropyrimidinase-like2p23.3 5 NM_001253723; NM_001253724; NM_020134; ENST00000288699; ENST00000401478; BC002874; OTTHUMT00000214187; OTTHUMT00000324739; OTTHUMT00000324740; OTTHUMT00000324741; OTTHUMT00000324742; OTTHUMT00000324743; uc002rhu.4; uc002rhv.4; uc021vev.1 1.52 0.0075 0.4468 DQ601004; uc021swo.1 FMNL3 -1.33 0.0076 0.4482 formin like 3 12q13.12 NM_175736; NM_198900; ENST00000335154; ENST00000352151; ENST00000550488; ENST00000550668; AK127200; BC090955; BC159100; uc001rut.1; uc001ruu.1; uc001ruv.1; uc001ruw.1; ENST00000293590 -1.47 0.0076 0.4492 DQ577092; uc021yaj.1 AGAP1 -1.33 0.0077 0.4527 ArfGAP with GTPase2q37 domain,NM_001037131; ankyrin repeat and NM_001244888; PH domain 1 NM_014914; ENST00000304032; ENST00000336665; ENST00000409457; ENST00000409538; ENST00000428334; BC140856; BC167153; BC167157; OTTHUMT00000257076; OTTHUMT00000257077; OTTHUMT00000329672; OTTHUMT00000329673; OTTHUMT00000329674; OTTHUMT00000329675; OTTHUMT00000329676; OTTHUMT00000329677; OTTHUMT00000329678; OTTHUMT00000329679; uc002vvs.3; uc002vvt.3; uc021vyp.1 RB1 1.34 0.0077 0.4527 retinoblastoma13q14.2 1 NM_000321; ENST00000267163; ENST00000484879; AY429568; BC039060; BC040540; M19701; OTTHUMT00000044883; OTTHUMT00000044884; OTTHUMT00000044885; OTTHUMT00000044886; uc001vcb.3; uc010acs.1; uc010act.1; ENST00000542917 SIX2 1.34 0.0078 0.4527 SIX homeobox 2p212 NM_016932; ENST00000303077; BC024033; OTTHUMT00000326188; uc002ruo.3 1.41 0.0078 0.4527 ENST00000459015 HLA-B -1.44 0.008 0.4591 major histocompatibility6p21.3 complex,NM_005514; class I, B AK124160; AK310586; BC013187; BC091497; M64259; OTTHUMT00000314270; OTTHUMT00000314271; OTTHUMT00000314272; OTTHUMT00000314273; OTTHUMT00000314274; OTTHUMT00000314275; OTTHUMT00000314276; OTTHUMT00000314277; uc011imy.2; uc011imz.2; uc011inb.1; uc011ina.1 -1.63 0.0081 0.4606 ENST00000516519 -1.57 0.0082 0.4629 ENST00000410379 APLP1 -1.31 0.0083 0.4666 amyloid beta (A4)19q13.1 precursor-likeNM_001024807; protein 1 NM_005166; ENST00000221891; ENST00000537454; AK092376; AK297339; AK297640; BC012889; uc002oce.3; uc002ocf.3; uc002ocg.3; uc010xsz.2; uc010xta.2 1.53 0.0083 0.4666 ENST00000384401 -1.46 0.0083 0.4666 DQ571863; uc021yxq.1 -1.45 0.0083 0.4666 ENST00000459103 PAGR1 -1.34 0.0084 0.4668 PAXIP1 associated16p11.2 glutamate-richNM_024516; protein 1ENST00000320330; BC003640; uc002dug.4; OTTHUMT00000255159 -1.41 0.0084 0.4668 ENST00000424630; OTTHUMT00000348210 CCNF -1.48 0.0085 0.4668 cyclin F 16p13.3 NM_001761; ENST00000293968; ENST00000397066; AB208829; BC012349; OTTHUMT00000250801; uc002cqd.1; uc002cqe.1 MIR1256 -1.51 0.0085 0.4668 microRNA 1256 NR_031657; uc021pth.1 -1.36 0.0085 0.4675 ENST00000517140 CLDN1 -1.77 0.0086 0.4682 claudin 1 3q28-q29 NM_021101; ENST00000295522; BC012471; OTTHUMT00000343516; OTTHUMT00000343561; uc003fsh.3; ENST00000545382 -1.4 0.0086 0.4682 DQ587962; uc010uia.1 -1.37 0.0086 0.4675 ENST00000516499 -1.56 0.0086 0.4675 AF520792; uc003vcq.1 -1.93 0.0087 0.4687 DQ594582; uc021zzj.1 -1.37 0.0087 0.4687 ENST00000517134 ZBTB24 -1.34 0.0088 0.4702 zinc finger and6q21 BTB domain containingNM_001164313; 24 NM_014797; ENST00000230122; AK309697; BC117374; BC143843; BX648883; OTTHUMT00000041758; uc003ptl.1; uc003ptm.3; uc010kds.1; uc010kdt.1; uc011ear.1 RNU105C 1.4 0.0089 0.4702 RNA, U105C small8q11.23 nucleolar ENST00000362342 SHISA9 -1.35 0.0089 0.4702 shisa family member16p13.12 9 NM_001145204; NM_001145205; ENST00000423335; ENST00000482916; ENST00000558583; OTTHUMT00000334564; OTTHUMT00000334571; OTTHUMT00000334572; uc002dcd.2; uc010uyy.2; ENST00000558318 1.42 0.0089 0.4702 DQ574249; uc002gyb.1 1.42 0.0089 0.4702 DQ570768; uc021tro.1 MIR550B2 -1.36 0.0091 0.4702 microRNA 550b-2 NR_037514; uc022abl.1 1.37 0.0091 0.4702 DQ573684; uc021sfb.1 1.37 0.0091 0.4702 DQ573684; uc010tzo.1; uc010tzo.2 1.31 0.0091 0.4702 ENST00000445166; OTTHUMT00000011055 1.37 0.0091 0.4702 DQ573684; uc021wki.1 1.37 0.0091 0.4702 DQ591735; uc010zau.1; uc010zau.2 1.37 0.0091 0.4702 DQ573684; uc021rnm.1 1.37 0.0091 0.4702 DQ599717; uc021rna.1 1.37 0.0091 0.4702 DQ599717; uc021rng.1 1.37 0.0091 0.4702 DQ599717; uc021rnh.1 -1.45 0.0092 0.471 DQ592825; uc002har.2; uc002har.3 -1.41 0.0092 0.4702 ENST00000415509; OTTHUMT00000050846 1.34 0.0093 0.4713 ENST00000516876 -1.32 0.0093 0.4717 ENST00000516274 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by-1.32 peer review) is0.0094 the author/funder.0.4718 All rights reserved. No reuse allowed withoutENST00000560268 permission. -1.56 0.0094 0.4724 ENST00000517099 DYM -1.35 0.0096 0.4758 dymeclin 18q21.1 NM_017653; ENST00000269445; ENST00000418472; ENST00000442713; AK225205; AK296579; BC064394; DQ925676; OTTHUMT00000255912; uc002ldi.1; uc002ldj.3; uc010dov.1; uc010xdf.1 KCNH4 -1.56 0.0096 0.4759 potassium channel,17q21.2 voltage gatedNM_012285; eag related ENST00000264661; subfamily H, member uc002hzb.2 4 1.78 0.0097 0.476 DQ593003; uc021rxn.1 -1.31 0.0098 0.4778 ENST00000429293; OTTHUMT00000011553 1.35 0.0098 0.4781 ENST00000427804; OTTHUMT00000010342 -1.34 0.0098 0.4781 BC062763; uc001tgo.1 MURC -1.42 0.0099 0.4787 muscle-related9q31.1 coiled-coil proteinNM_001018116; ENST00000307584; BC090888; OTTHUMT00000053419; uc004bba.3 1.39 0.0099 0.4781 ENST00000555313; ENST00000556652 -1.37 0.0099 0.4781 OTTHUMT00000364977 RP11-423H2.2 -1.51 0.0099 0.4781 OTTHUMT00000373213; ENST00000503449 1.31 0.01 0.4798 ENST00000415575; OTTHUMT00000039801 1.61 0.01 0.4798 DQ579335; uc022bcp.1 1.32 0.01 0.4798 ENST00000516650 1.41 0.0101 0.4829 AF079515; uc004coz.1 LOC100128088 1.31 0.0102 0.4854 matrix metallopeptidase11q22.2 1-likeAB231724; ENST00000416164; uc001phf.2; uc001phf.3 TRAF3 -1.37 0.0104 0.4892 TNF receptor-associated14q32.32 factorNM_001199427; 3 NM_003300; NM_145725; NM_145726; ENST00000347662; ENST00000351691; ENST00000392745; ENST00000539721; ENST00000560371; BC075086; uc001ymc.2; uc001ymd.2; uc001yme.2; uc010txy.2 MIR539 1.81 0.0105 0.4902 microRNA 53914q32.31 NR_030256; uc021sdg.1; ENST00000365690 SIAH3 -1.36 0.0105 0.4904 siah E3 ubiquitin13q14.13 protein ligaseNM_198849; family member ENST00000400405; 3 OTTHUMT00000044788; uc001vap.3; ENST00000471241; OTTHUMT00000343033 ANKRD18DP -1.31 0.0106 0.4911 ankyrin repeat3q29 domain 18D, pseudogeneNR_003291; ENST00000435620; BC053879; uc003fyx.3; uc010iat.2 TMEM65 -1.43 0.0107 0.4927 transmembrane8q24.13 protein 65 NM_194291; ENST00000297632; BC032396; BC041379; OTTHUMT00000381464; uc010mdl.3 XYLT1 -1.5 0.0107 0.4911 xylosyltransferase16p12.3 I NM_022166; ENST00000261381; OTTHUMT00000252241; uc002dfa.3 TRIM49D2; TRIM49D1 1.35 0.0108 0.495 tripartite motif11q14.3 containing 49D2;NM_001105522; tripartite motif NM_001206627; containing 49D1 uc009yvu.3 KRTAP5-6 1.58 0.0109 0.4963 keratin associated11p15.5 protein 5-6NM_001012416; ENST00000382160; BC130399; OTTHUMT00000102339; uc001lua.3 -1.42 0.011 0.4973 DQ570895; uc002ndc.2; uc002ndc.3 1.35 0.011 0.4967 AY748447; uc001yry.1 1.31 0.011 0.4967 ENST00000426063 -1.37 0.0111 0.5004 ENST00000419703; OTTHUMT00000042901 -1.9 0.0113 0.5021 DQ582888; uc021qii.1 PDE1B -1.35 0.0114 0.5031 phosphodiesterase12q13 1B, calmodulin-dependentNM_000924; NM_001165975; ENST00000243052; ENST00000394277; ENST00000538346; ENST00000550620; AK126899; AK296422; AK302899; BC032226; BX538092; uc001sgd.2; uc001sge.3; uc001sgf.3; uc009znq.3; uc010soz.2; uc010spa.1 SLCO3A1 -1.44 0.0114 0.5031 solute carrier organic15q26 anion transporterNM_001145044; family, NM_013272; member 3A1 ENST00000318445; ENST00000424469; ENST00000555549; ENST00000555769; AK097797; AK310306; BC000585; OTTHUMT00000313529; uc002bqx.2; uc002bqy.2; uc002bqz.1; uc010boc.1 MIR4804 -1.3 0.0115 0.5047 microRNA 4804 NR_039968; uc021yal.1 TMSB15A -1.39 0.0115 0.5047 thymosin betaXq21.33-q22.3 15a NM_021992; ENST00000289373; BC000183; OTTHUMT00000057621; uc004eje.3 E2F7 -1.31 0.0116 0.5052 E2F transcription12q21.2 factor 7 NM_203394; ENST00000322886; ENST00000416496; BC016658; BC136366; uc001sym.4; uc009zse.3; ENST00000339887 PELI2 -1.3 0.0116 0.5064 pellino E3 ubiquitin14q21 protein ligaseNM_021255; family member ENST00000267460; 2 BC009476; OTTHUMT00000276925; uc001xch.3 1.57 0.0116 0.5062 ENST00000364172 2.44 0.0117 0.5087 DQ594304; uc010ufx.1; uc010ufx.2 CYP1B1 -1.63 0.0118 0.5094 cytochrome P450,2p22.2 family 1, subfamilyOTTHUMT00000325647 B, polypeptide 1 -1.59 0.0118 0.5094 ENST00000441587; OTTHUMT00000327862 GOPC -1.41 0.0119 0.5096 golgi-associated6q21 PDZ and coiled-coilNM_001017408; motif containing NM_020399; ENST00000052569; ENST00000368498; ENST00000535237; AJ420595; BC009553; OTTHUMT00000041987; OTTHUMT00000041988; uc003pxu.3; uc003pxv.3; uc010keg.2 1.36 0.0119 0.5096 ENST00000384400 MIR548H4 -1.37 0.012 0.5105 microRNA 548h-4 NR_031680; uc021spl.1 RBBP9 -1.35 0.012 0.5107 retinoblastoma20p11.2 binding proteinNM_006606; 9 ENST00000337227; ENST00000493184; BC015938; OTTHUMT00000078175; OTTHUMT00000078177; OTTHUMT00000078178; uc002wqy.3; ENST00000339848 GABRQ -1.5 0.0121 0.5118 gamma-aminobutyricXq28 acid (GABA)NM_018558; A receptor, BC109210; theta OTTHUMT00000058763; uc004ffp.1; ENST00000333733 1.37 0.0121 0.5118 ENST00000410247; 7SK; uc021ujh.1 1.4 0.0122 0.5118 uc022aoq.1 C1orf54 -1.39 0.0123 0.515 chromosome 11q21.2 open readingNM_024579; frame 54 ENST00000369098; ENST00000369099; ENST00000369102; BC017761; OTTHUMT00000035053; OTTHUMT00000035054; OTTHUMT00000035055; uc001euc.3; uc001eud.3; uc001eue.3 1.63 0.0123 0.5135 ENST00000411281; uc021qyi.1 IGHV1-8 1.31 0.0125 0.5185 immunoglobulin heavy variableENST00000390599; 1-8 OTTHUMT00000325672 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by1.39 peer review) is0.0125 the author/funder.0.5185 All rights reserved. No reuse allowed withoutENST00000458972 permission. PAX7 -1.48 0.0126 0.5185 paired box 7 1p36.13 NM_001135254; NM_002584; NM_013945; ENST00000375375; ENST00000400661; ENST00000420770; BC121165; BC121166; OTTHUMT00000006928; OTTHUMT00000372482; OTTHUMT00000372483; uc001bay.3; uc001baz.3; uc010oct.2 PARM1 -1.41 0.0126 0.5185 prostate androgen-regulated4q13.3-q21.3 NM_015393; mucin-like protein ENST00000307428; 1 ENST00000513238; BC013294; OTTHUMT00000362494; OTTHUMT00000362495; uc003hih.2 1.33 0.0126 0.5185 DQ570033; uc002ajf.2; uc002ajf.3 1.42 0.0126 0.5185 DQ591664; uc022bir.1 MIR4718 1.32 0.0127 0.5197 microRNA 4718 NR_039869; uc021tdb.1 RNF141 -1.33 0.0129 0.5197 ring finger protein11p15.4 141 NM_016422; ENST00000265981; ENST00000528665; AK309367; BC018104; uc001mis.1; uc009yga.1 -1.38 0.0129 0.5197 uc021pyq.1 -1.37 0.0131 0.5229 DQ597986; uc021swt.1 1.39 0.0131 0.5224 ENST00000457477; OTTHUMT00000096287 -1.33 0.0131 0.5224 ENST00000435106; OTTHUMT00000046741 1.35 0.0133 0.5242 ENST00000459153 -1.47 0.0133 0.5241 DQ571357; uc010lcl.3 ANKFY1 -1.43 0.0134 0.5247 ankyrin repeat17p13.3 and FYVE domainNM_016376; containing NM_020740; 1 ENST00000341657; AB037360; AK025483; AK057047; AK302712; uc002fxn.3; uc002fxo.3; uc002fxp.3; uc002fxq.1; uc010ckp.3; uc010vrz.2; ENST00000433651; ENST00000535427; uc002fxr.3 PLPPR2 -1.32 0.0134 0.5247 phospholipid phosphatase19p13.2 relatedNM_001170635; 2 NM_022737; ENST00000251473; BC009378; CR936652; uc002mre.2; uc002mrf.2; uc010dxy.2 -1.45 0.0134 0.5251 ENST00000459555 1.41 0.0135 0.5253 ENST00000459515 GATSL2 -1.56 0.0136 0.5255 GATS protein-like7q11.23 2 AL832384; uc003ubq.3; uc003ubq.4 2.13 0.0138 0.5257 DQ594846; uc010uhe.1; uc010uhe.2 NPTXR -1.36 0.0139 0.5257 neuronal pentraxin22q13.1 receptor NM_014293; ENST00000333039; OTTHUMT00000318194; uc003awk.3 LOC101928047 -1.36 0.0139 0.5257 uncharacterized LOC101928047BC039678; ENST00000501751; uc003mxa.3 1.38 0.0139 0.5257 ENST00000364863 -1.74 0.014 0.5264 DQ596823; uc002beh.1; uc002beh.2 B4GALT5 -1.31 0.0141 0.5267 UDP-Gal:betaGlcNAc20q13.1-q13.2 beta 1,4-NM_004776; galactosyltransferase, ENST00000371711; polypeptide BC074821; 5 BC104987; OTTHUMT00000080543; uc002xuu.4 -1.65 0.0141 0.5264 ENST00000408505 LOC100288842 -1.31 0.0142 0.528 UDP-GlcNAc:betaGal9q33.2 beta-1,3-N-acetylglucosaminyltransferaseNR_027442; ENST00000540063; uc011lyd.1; 5 pseudogene OTTHUMT00000053832 LOC100379224 -1.36 0.0142 0.528 uncharacterized19q13.2 LOC100379224NR_033341; uc002oyi.3 NKAIN2 -1.48 0.0144 0.531 Na+/K+ transporting6q21 ATPase NM_001040214;interacting 2 NM_153355; ENST00000368416; ENST00000368417; ENST00000476571; ENST00000545433; ENST00000546092; AB070452; AK309385; AK309802; BC035062; OTTHUMT00000042056; OTTHUMT00000042057; OTTHUMT00000042058; uc003pzn.1; uc003pzo.3; uc003pzp.3; uc010kep.1; uc010keq.3; uc010ker.3; ENST00000539866 1.39 0.0144 0.531 ENST00000557174 DPY19L2P1 -1.46 0.0145 0.5322 DPY19L2 pseudogene7p14.2 1 NR_002833; BC013598; BC066987; BX648666; ENST00000436258; uc003tep.1; uc003teq.1; uc010kwz.1 -1.76 0.0145 0.5311 ENST00000384794 1.35 0.0145 0.5328 ENST00000557800 1.37 0.0145 0.5322 ENST00000517154; 7SK 1.4 0.0145 0.5322 ENST00000428410; OTTHUMT00000195552 1.48 0.0145 0.5322 ENST00000424015 -1.59 0.0145 0.5311 ENST00000507144 2.08 0.0147 0.533 DQ570864; uc001mzs.1 MIR1264 1.79 0.0148 0.533 microRNA 1264 NR_031563; uc022ccy.1 -1.79 0.0148 0.533 DQ598345; uc010vck.1 1.36 0.0148 0.533 ENST00000390964 1.44 0.0149 0.5353 DQ591331; uc001qlw.1 SCD5 -1.44 0.015 0.5361 stearoyl-CoA desaturase4q21.22 5 NM_001037582; NM_024906; ENST00000273908; ENST00000319540; BC004936; BC137429; BC137432; OTTHUMT00000252635; OTTHUMT00000252636; uc003hna.2; uc003hnb.4; uc003hnc.3; ENST00000282709 MBD3L2 -1.79 0.0151 0.5361 methyl-CpG binding19p13.2 domain proteinNM_144614; 3-like ENST00000381393;2 uc010dvf.1; ENST00000412046 -1.39 0.0151 0.5361 ENST00000411390 -1.42 0.0151 0.5361 ENST00000521408; OTTHUMT00000375939 LOC100507351 -1.39 0.0153 0.5397 uncharacterized LOC100507351NR_040050; uc021udz.1 -1.44 0.0155 0.5418 ENST00000364921 1.5 0.0155 0.5418 uc021ves.1 1.38 0.0156 0.5426 ENST00000365439 PKM -1.31 0.0157 0.543 pyruvate kinase,15q22 muscle NM_001206796; NM_001206797; NM_001206798; NM_001206799; NM_002654; NM_182470; NM_182471; ENST00000319622; ENST00000335181; ENST00000389093; ENST00000449901; AK308264; BC000481; BC007640; BC007952; BC012811; BC035198; BC035487; BC094767; BC096823; uc002atr.1; uc002atv.2; uc002atw.2; uc002atx.2; uc002aty.2; uc010bit.1; uc010biu.1; uc010uki.2; uc010ukj.2; uc010ukk.2; ENST00000327974; ENST00000434220 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by-1.66 peer review) is0.0157 the author/funder. 0.543All rights reserved. No reuse allowed withoutENST00000516707 permission. SCARNA1 1.71 0.0158 0.543 small Cajal body-specific1p35.3 RNANR_002997; 1 ENST00000517138; uc001boy.1 SNORA24 1.62 0.0158 0.543 small nucleolar4q26 RNA, H/ACA boxNR_002963; 24 ENST00000384096; uc003ibz.1 -1.44 0.0162 0.5458 ENST00000516769; uc021oie.1 -1.43 0.0162 0.5458 ENST00000516465 -1.51 0.0163 0.5458 DQ588687; uc021szh.1 -1.51 0.0163 0.5458 DQ578838; uc001ytp.2; uc001ytp.3 -1.51 0.0163 0.5458 DQ578838; uc021sfn.1 -1.51 0.0163 0.5458 DQ588687; uc010tzw.1 -1.51 0.0163 0.5458 DQ588687; uc002cdz.2; uc002cdz.3 -1.51 0.0163 0.5458 DQ588687; uc001zce.1 -1.51 0.0163 0.5458 DQ578838; uc021sfr.1 -1.51 0.0163 0.5458 DQ578838; uc001ywe.2; uc001ywe.3 -1.51 0.0163 0.5458 DQ578838; uc001zcw.1 -1.51 0.0163 0.5458 DQ578838; uc021shc.1 -1.51 0.0163 0.5458 DQ578838; uc021sgk.1 -1.51 0.0163 0.5458 DQ578838; uc010ukq.1 1.36 0.0166 0.5506 ENST00000410712 1.33 0.0167 0.5514 uc021tdj.1 1.33 0.0167 0.5514 uc021tdu.1 1.33 0.0167 0.5514 uc021teb.1 MIR208B -1.36 0.0168 0.5545 microRNA 208b14q11.2 NR_030624; ENST00000401172; uc021rqy.1 PPA1 -1.38 0.0168 0.5527 pyrophosphatase10q11.1-q24 (inorganic) NM_021129;1 ENST00000373230; ENST00000373232; ENST00000460755; BC001022; BC061581; BC105034; BC107882; OTTHUMT00000048490; OTTHUMT00000048491; OTTHUMT00000048492; OTTHUMT00000048493; uc001jqv.1 1.35 0.0169 0.5547 ENST00000520268; OTTHUMT00000380527 MMP13 -1.34 0.017 0.555 matrix metallopeptidase11q22.3 13 NM_002427; ENST00000260302; ENST00000340273; BC067522; BC074807; uc001phl.3; ENST00000546012 MFSD14C -1.33 0.0171 0.555 major facilitator9q22.33 superfamily NR_002894;domain containing OTTHUMT00000053305; 14C OTTHUMT00000053296; ENST00000375223; ENST00000506067; uc004aws.3 MLLT10P1 1.37 0.0171 0.555 myeloid/lymphoid or mixed-lineageNR_045115; leukemia; uc021wbp.1 translocated to, 10 pseudogene 1 1.66 0.0172 0.555 ENST00000363683 WSPAR 1.35 0.0174 0.5564 WNT signaling pathway activatingENST00000513561; non-coding RNA OTTHUMT00000371468 HLA-A -1.32 0.0175 0.557 major histocompatibility6p21.3 complex,AF287958; class I,AK125608; A AK301019; BC003069; BC008611; BC019236; M27539; OTTHUMT00000311809; OTTHUMT00000311810; OTTHUMT00000311811; OTTHUMT00000311812; OTTHUMT00000311813; OTTHUMT00000311814; OTTHUMT00000311815; uc011hka.1; uc011hkb.2; uc021zrd.1; uc011hjw.2; uc011hjy.2 1.42 0.0175 0.5574 ENST00000410561 HSPH1 -1.32 0.0176 0.5574 heat shock 105kDa/110kDa13q12.3 proteinNM_006644; 1 ENST00000320027; ENST00000380405; ENST00000445273; ENST00000469538; AB003333; AK302294; AK302430; AK303029; AK307597; AK311464; BC018124; BC037553; OTTHUMT00000044384; OTTHUMT00000044385; OTTHUMT00000044386; OTTHUMT00000044387; OTTHUMT00000044388; uc001utj.3; uc001utk.3; uc001utl.3; uc010aaw.3; uc010aax.1; uc010aay.1; uc010tds.2; uc010tdt.1; ENST00000380363; ENST00000380406; ENST00000429785; ENST00000438061 SNORD60 1.59 0.0178 0.5595 small nucleolar16p13.3 RNA, C/D boxNR_002736; 60 ENST00000383903; uc002cov.1 -1.36 0.0179 0.5595 OTTHUMT00000077214 1.34 0.0179 0.5595 ENST00000408271 1.57 0.018 0.5595 DQ572786; uc001nai.2; uc001nai.3 MIR4659A -1.63 0.0181 0.5595 microRNA 4659a NR_039803; uc022aqt.1 -1.55 0.0181 0.5595 DQ582680; uc021ssp.1 -1.55 0.0181 0.5595 DQ582680; uc021sst.1 -1.55 0.0181 0.5595 DQ582680; uc021stb.1 -1.55 0.0181 0.5595 DQ582680; uc021std.1 -1.55 0.0181 0.5595 DQ582680; uc021sth.1 -1.55 0.0181 0.5595 DQ576060; uc021sts.1 -1.55 0.0181 0.5595 DQ576060; uc021stq.1 -1.55 0.0181 0.5595 DQ576060; uc010unz.1; uc010unz.2 -1.44 0.0181 0.5595 DQ596700; uc002ncp.2 -1.55 0.0181 0.5595 DQ582680; uc022coq.1 -1.55 0.0181 0.5595 DQ576060; uc022cpd.1 -1.38 0.0183 0.5603 ENST00000363871 RBM15 -1.5 0.0184 0.5605 RNA binding motif1p13 protein 15BC069739; uc001dzn.1 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by1.35 peer review) is0.0184 the author/funder.0.5605 All rights reserved. No reuse allowed withoutENST00000424162; permission. OTTHUMT00000041683 NLK -1.31 0.0185 0.5605 nemo-like kinase17q11.2 NM_016231; ENST00000407008; BC064663; OTTHUMT00000255607; OTTHUMT00000255608; uc010crj.3 ISOC1 -1.57 0.0186 0.5606 isochorismatase5q22.1-q33.3 domain containingNM_016048; 1 ENST00000173527; BC008367; BC014105; OTTHUMT00000371826; OTTHUMT00000371827; uc003kva.3; OTTHUMT00000371828; OTTHUMT00000371829 1.4 0.0187 0.5614 ENST00000390888 EWSAT1 -1.39 0.0189 0.5638 Ewing sarcoma15q23 associated transcriptNR_026949; 1 ENST00000415504; ENST00000440444; ENST00000558922; ENST00000559914; ENST00000559964; AK097560; AK292174; ENST00000559870; OTTHUMT00000257119; OTTHUMT00000257120; OTTHUMT00000257121; uc002art.3; uc002arv.3; uc010big.2; uc010big.3 LINC01492 1.41 0.019 0.5638 long intergenic9q31.1 non-protein codingENST00000425157; RNA 1492 OTTHUMT00000053465 1.45 0.019 0.5638 ENST00000390747 -1.5 0.0191 0.5638 ENST00000516141; uc021pqs.1 RNY4P8 -1.37 0.0192 0.5638 RNA, Ro-associated Y4 pseudogeneENST00000363865 8 1.32 0.0193 0.5653 uc021yns.1 IER3 -1.37 0.0194 0.5653 immediate early6p21.3 response 3 NM_003897; BC000844; BC005080; OTTHUMT00000077309; OTTHUMT00000077310; uc011ezw.2 IER3 -1.37 0.0194 0.5653 immediate early6p21.3 response 3 NM_003897; BC000844; BC005080; OTTHUMT00000309889; OTTHUMT00000309890; uc011fyj.2 IER3 -1.37 0.0194 0.5653 immediate early6p21.3 response 3 NM_003897; BC000844; BC005080; OTTHUMT00000311026; OTTHUMT00000311027; uc011gum.2 IER3 -1.37 0.0194 0.5653 immediate early6p21.3 response 3 NM_003897; BC000844; BC005080; OTTHUMT00000258037; OTTHUMT00000258038; uc011jhl.2 MIR4765 1.45 0.0195 0.5664 microRNA 4765 NR_039922; uc021vfs.1 PFKP -1.3 0.0195 0.567 phosphofructokinase,10p15.3-p15.2 plateletNM_001242339; NM_002627; ENST00000381072; ENST00000381075; ENST00000381125; ENST00000460445; AK128373; AK308003; AK308226; AK309692; BC002536; BC029138; OTTHUMT00000046452; OTTHUMT00000046453; OTTHUMT00000046454; OTTHUMT00000046455; OTTHUMT00000046456; OTTHUMT00000046457; OTTHUMT00000046458; OTTHUMT00000046459; OTTHUMT00000046460; OTTHUMT00000046461; OTTHUMT00000046462; uc001igp.3; uc001igq.3; uc009xhr.3; uc009xhs.1; uc009xht.3; uc009xhu.3; ENST00000397834 LOC102724849 1.41 0.0195 0.5664 uncharacterized2q35 LOC102724849ENST00000447835; OTTHUMT00000337320 THAP1 -1.31 0.0196 0.5675 THAP domain containing,8p11.21 apoptosisNM_018105; associated NM_199003; protein 1 ENST00000254250; ENST00000345117; ENST00000532093; BC021721; uc003xpk.3; uc003xpl.3 2.08 0.0196 0.5674 DQ571738; uc021yye.1 ASS1 1.76 0.0197 0.5676 argininosuccinate9q34.1 synthase 1NM_000050; NM_054012; ENST00000352480; ENST00000372393; ENST00000372394; ENST00000493984; AK027126; BC009243; BC021676; OTTHUMT00000054649; OTTHUMT00000054650; OTTHUMT00000054651; OTTHUMT00000054652; OTTHUMT00000054653; OTTHUMT00000054654; OTTHUMT00000054655; OTTHUMT00000054656; OTTHUMT00000054657; OTTHUMT00000054658; uc004bzm.3; uc004bzn.3; uc010mza.3; ENST00000334909 OR10P1 1.38 0.0197 0.5676 olfactory receptor,12q13.2 family 10,NM_206899; subfamily P, ENST00000309675;member 1 BC136914; uc010spq.2 SCNN1G -1.72 0.0197 0.5676 sodium channel,16p12 non voltageNM_001039; gated 1 gamma ENST00000300061; subunit BC059391; BC069652; OTTHUMT00000254496; uc002dlm.1 MIR151A -1.42 0.0199 0.5697 microRNA 151a ENST00000385057; OTTHUMT00000378059; ENST00000521276; uc022bbw.1 -1.4 0.02 0.5711 ENST00000555969 KCTD9 -1.34 0.0202 0.5739 potassium channel8p21.1 tetramerizationNM_017634; domain ENST00000221200; containing 9 ENST00000519665; AK298518; BC021216; BC068518; OTTHUMT00000216890; OTTHUMT00000375808; OTTHUMT00000375809; OTTHUMT00000375810; OTTHUMT00000375922; OTTHUMT00000375923; OTTHUMT00000375924; OTTHUMT00000375925; OTTHUMT00000375926; OTTHUMT00000375927; OTTHUMT00000375928; uc003xeo.3; uc011lad.2 LOC728485 -1.34 0.0202 0.5737 uncharacterized19q13.12 LOC728485 BC024306; ENST00000500464; uc002oes.1; uc002oet.2; uc002oet.3 1.35 0.0203 0.5742 ENST00000516777 -1.82 0.0204 0.5747 ENST00000384114 DEFB113 1.53 0.0207 0.5771 defensin, beta 6p12.3113 NM_001037729; ENST00000398718; OTTHUMT00000359666; uc011dwq.2 -1.58 0.0208 0.5771 ENST00000516834 -1.46 0.0209 0.5783 ENST00000459595 -1.3 0.0211 0.5791 ENST00000390145 C1DP3 -1.38 0.0212 0.5802 C1D nuclear receptor corepressorENST00000412019 pseudogene 3 PPME1 -1.61 0.0212 0.5803 protein phosphatase11q13.4 methylesteraseNM_016147; 1 ENST00000328257; ENST00000398427; ENST00000542710; ENST00000543525; AF111853; AK225647; BC003046; BC050705; uc001oux.3; uc001ouw.3; uc009yty.3 HIST1H4K -1.4 0.0218 0.5849 histone cluster6p22.1 1, H4k NM_003541; BC111093; BC111434; OTTHUMT00000040156; uc003njr.3 -1.35 0.0219 0.5857 ENST00000507241; OTTHUMT00000370998 TAF9B -1.35 0.022 0.586 TAF9B RNA polymeraseXq13.1-q21.1 II, TATANM_015975; box binding ENST00000341864; protein (TBP)-associated BC009566; factor, BC010350; 31kDa BC071649; BC146952; BC146960; OTTHUMT00000057308; OTTHUMT00000057309; uc004eda.3 ZNF317 -1.3 0.0223 0.5869 zinc finger protein19p13 317 NM_001190791; NM_020933; ENST00000247956; ENST00000360385; ENST00000419608; AF307096; AF307097; AK304151; BC009367; BC078154; uc002mku.3; uc002mkv.3; uc002mkw.3; uc002mkx.3; uc002mky.3; uc010xkm.2 -1.88 0.0223 0.5869 ENST00000459334 CSN1S1 1.3 0.0225 0.5869 casein alpha s14q21.1 NM_001025104; NM_001890; ENST00000246891; ENST00000505782; ENST00000507763; ENST00000507772; BC128227; BC128228; DQ064604; uc003hep.1; uc003heq.1; uc003her.1; ENST00000354865; ENST00000444405; OTTHUMT00000362629; OTTHUMT00000362630; OTTHUMT00000362631; OTTHUMT00000362632; OTTHUMT00000362633 SNORD115-38 1.38 0.0225 0.5869 small nucleolar15q11.2 RNA, C/D boxNR_003353; 115-38 ENST00000365037; uc001zag.1 -1.46 0.0225 0.5869 DQ583847; uc021shg.1 -1.46 0.0225 0.5869 DQ583847; uc001zgl.2; uc001zgl.3 -1.46 0.0225 0.5869 DQ577333; uc001zda.2; uc001zda.3 -1.46 0.0225 0.5869 DQ577333; uc001zem.2; uc001zem.3 -1.54 0.0225 0.5869 ENST00000515950; 7SK; uc021xgz.1 PREX1 -1.39 0.0229 0.5898 phosphatidylinositol-3,4,5-trisphosphate-dependent20q13.13 NM_020820; ENST00000371941; Rac exchange ENST00000496915; factor 1 AL136579; OTTHUMT00000079623; OTTHUMT00000079624; OTTHUMT00000079625; uc002xtv.1; uc002xtw.1; ENST00000396220; uc021wer.1 1.59 0.0229 0.5898 ENST00000390750 -1.39 0.0231 0.5905 uc021vrg.1 PRR5L -1.5 0.0232 0.5905 proline rich 5 like11p13-p12 NM_001160167; NM_001160168; NM_001160169; NM_024841; ENST00000378867; ENST00000389693; ENST00000527487; ENST00000530639; uc001mwo.4; uc001mwp.3; uc009ykk.3; uc010rfc.2; ENST00000311599 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by-1.47 peer review) is0.0232 the author/funder.0.5905 All rights reserved. No reuse allowed withoutENST00000517279 permission. 1.45 0.0233 0.5905 uc021ypf.1 1.45 0.0234 0.5909 ENST00000516998 -1.55 0.0234 0.591 ENST00000446917 1.35 0.0234 0.5909 ENST00000432535; OTTHUMT00000048153 OLFM1 -1.34 0.0236 0.5911 olfactomedin 19q34.3 NM_006334; NM_014279; ENST00000252854; ENST00000277415; ENST00000371793; ENST00000371796; ENST00000371799; ENST00000371801; ENST00000392991; AK090818; AK290478; BC000189; BC008763; OTTHUMT00000054971; OTTHUMT00000054972; OTTHUMT00000054973; OTTHUMT00000054974; OTTHUMT00000054975; OTTHUMT00000054976; OTTHUMT00000054977; uc004cfk.4; uc004cfl.4; uc004cfn.4; uc010naq.2; uc010nar.3 -2.65 0.0237 0.5914 DQ589785; uc010ufw.1 1.69 0.0237 0.5914 DQ588542; uc021oit.1 C2CD3 -1.35 0.0238 0.5918 C2 calcium-dependent11q13.4 domainNM_015531; containing 3ENST00000313663; ENST00000334126; ENST00000539061; ENST00000542452; BC035599; uc001out.3; uc001ouu.2; ENST00000289350; ENST00000313681; uc001ouv.2 CHAC1 2.22 0.0238 0.5918 ChaC glutathione-specific15q15.1 gamma-glutamylcyclotransferaseNM_001142776; NM_024111; 1ENST00000444189; ENST00000446533; ENST00000487220; BC001683; BC019625; OTTHUMT00000252526; OTTHUMT00000347784; uc001znh.2; uc010uct.1 1.46 0.0238 0.5918 ENST00000531886 1.47 0.0239 0.5932 OTTHUMT00000079505 1.33 0.024 0.5936 DQ581615; uc010vzr.1; uc010vzr.2 LINC01004 -1.46 0.0241 0.5947 long intergenic7q22.1 non-protein codingNR_039981; RNA 1004 uc003vcj.1; uc003vcj.2 MIR518C -1.34 0.0242 0.5948 microRNA 518c19q13.42 NR_030199; uc021vac.1; ENST00000384822 1.4 0.0242 0.5948 ENST00000364937 AIMP2 2.18 0.0244 0.5968 aminoacyl tRNA7p22 synthetase complex-interactingNM_006303; ENST00000223029; multifunctional ENST00000395236; protein 2 ENST00000400479; BC002853; BC013630; OTTHUMT00000242834; OTTHUMT00000325472; OTTHUMT00000325473; OTTHUMT00000325474; uc003spo.3 1.33 0.0244 0.5971 ENST00000459547 1.34 0.0245 0.5974 ENST00000459304 CACNA1H -1.41 0.0246 0.5976 calcium channel,16p13.3 voltage-dependent,NM_001005407; T type, alpha NM_021098; 1H subunit ENST00000348261; ENST00000358590; DQ363526; DQ363528; DQ363529; uc002cks.3; uc002ckt.3; uc002cku.3; uc002ckv.3; uc010brj.3 TMED8 -1.32 0.0246 0.5976 transmembrane14q24.3 p24 traffickingNM_213601; protein family ENST00000216468; member 8 BC101510; BX248262; uc001xtn.1; uc001xto.1 -1.3 0.0246 0.5976 ENST00000506010; OTTHUMT00000360544 -1.32 0.0247 0.5991 ENST00000390980 1.3 0.0248 0.5993 OTTHUMT00000365464 UBE2S -1.39 0.0249 0.6 ubiquitin-conjugating19q13.43 enzymeBC066948 E2S -1.56 0.0249 0.6 DQ587763; uc011dkq.1 -1.56 0.0249 0.6 DQ587763; uc011dxr.1 EGF -1.3 0.025 0.6002 epidermal growth4q25 factor NM_001178130; NM_001178131; NM_001963; ENST00000265171; ENST00000502723; ENST00000503392; ENST00000509793; AK307734; BC093731; BC113461; OTTHUMT00000255065; OTTHUMT00000363798; OTTHUMT00000363799; OTTHUMT00000363800; OTTHUMT00000363801; OTTHUMT00000363803; OTTHUMT00000363804; OTTHUMT00000363805; uc003hzy.4; uc010imk.3; uc011cfu.2; uc011cfv.2 PSAT1 2.17 0.0252 0.601 phosphoserine9q21.2 aminotransferaseNM_021154; 1 NM_058179; ENST00000347159; ENST00000376588; BC000971; BC004863; BC016645; BC018129; OTTHUMT00000052777; OTTHUMT00000052778; uc004ala.3; uc004alb.3 -1.5 0.0253 0.6021 ENST00000516597 -1.4 0.0253 0.6018 ENST00000459470 -1.39 0.0254 0.603 OTTHUMT00000125969 -1.31 0.0254 0.6034 ENST00000364195 IGHV3-48 1.37 0.0255 0.6043 immunoglobulin14q32.33 heavy variableOTTHUMT00000324605; 3-48 ENST00000390624 -1.35 0.0255 0.6038 DQ570642; uc001jys.2; uc001jys.3 -1.35 0.0255 0.6038 DQ599993; uc003yqm.1 1.37 0.0257 0.6046 1.37 0.0257 0.6046 ENST00000425077; OTTHUMT00000341782 TWISTNB -1.34 0.0258 0.6057 TWIST neighbor7p21.1 NM_001002926; ENST00000222567; BC014574; BC130298; BC130300; OTTHUMT00000326463; OTTHUMT00000326464; uc003sup.1 1.4 0.0258 0.6051 ENST00000430920 SNORA71C 1.39 0.0261 0.6077 small nucleolar20q11.23 RNA, H/ACA boxNR_003017; 71C ENST00000364642; uc002xin.1 IER3 -1.34 0.0262 0.6087 immediate early6p21.3 response 3 NM_003897; BC000844; BC005080; OTTHUMT00000035635; OTTHUMT00000035636; uc011ikl.2 -1.36 0.0262 0.6089 ENST00000516044 -1.37 0.0263 0.6092 ENST00000433526; OTTHUMT00000047063 SNORA70B 1.46 0.0264 0.6096 small nucleolar2p15 RNA, H/ACA boxNR_003707; 70B ENST00000384210; uc010fck.1 1.31 0.0264 0.6092 ENST00000516727 -1.36 0.0264 0.6096 ENST00000383983 PTPN13 -1.41 0.0265 0.6096 protein tyrosine4q21.3 phosphatase,NM_006264; non-receptor NM_080683; type 13 (APO-1/CD95 NM_080684; (Fas)-associated NM_080685; phosphatase)ENST00000316707; ENST00000411767; ENST00000427191; ENST00000436978; ENST00000502971; ENST00000511467; BC140777; BX647553; uc003hpy.3; uc003hpz.3; uc003hqa.3; uc003hqb.3; uc003hqc.1; ENST00000357349; OTTHUMT00000363189; OTTHUMT00000363190; OTTHUMT00000363191; OTTHUMT00000363193; OTTHUMT00000363194; OTTHUMT00000363196; OTTHUMT00000363197; OTTHUMT00000363198 STX18-IT1 1.46 0.0265 0.6096 STX18 intronic4p16.3 transcript 1 ENST00000515487; OTTHUMT00000358556 RNA5SP381 -1.5 0.0266 0.6096 RNA, 5S ribosomal pseudogeneENST00000516076 381 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by peer1.6 review) is0.0266 the author/funder.0.6096 All rights reserved. No reuse allowed withoutENST00000459310 permission. -1.35 0.0267 0.6097 ENST00000383968; uc022bba.1 1.34 0.0268 0.6097 ENST00000537079 1.32 0.0269 0.611 ENST00000363280; uc021scj.1 1.32 0.0271 0.6121 ENST00000458982 -1.43 0.0272 0.6132 ENST00000410937 VRK1 -1.37 0.0275 0.6145 vaccinia related14q32 kinase 1 NM_003384; ENST00000216639; ENST00000555067; BC103761; BC112075; BC113510; uc001yft.3 1.34 0.0275 0.6144 DQ597161; uc010vzn.1; uc010vzn.2 -1.39 0.0275 0.6144 ENST00000362530 HERPUD1 1.72 0.0276 0.6147 homocysteine-inducible,16q13 endoplasmicNM_001010989; reticulum NM_001010990; stress-inducible, NM_014685; ubiquitin-like ENST00000300302; domain member 1 ENST00000344114; ENST00000379792; ENST00000439977; AF217990; AK304800; BC000086; BC008320; BC009739; BC032673; DQ837586; OTTHUMT00000257056; uc002ekh.1; uc002eke.1; uc002ekf.1; uc002ekg.1; uc010cco.1; uc010ccp.1; uc010vhj.1 1.39 0.0276 0.6147 ENST00000459519 -1.33 0.0277 0.6147 ENST00000362604; uc021tdc.1 1.3 0.0281 0.6156 ENST00000391224 1.39 0.0281 0.6156 uc002imj.1 MIR148B 1.33 0.0283 0.6175 microRNA 148b12q13.13 NR_029894; ENST00000362252; uc010sou.2; uc010sou.1 1.3 0.0283 0.6177 uc004bdy.1 DGAT2 -1.36 0.0286 0.6191 diacylglycerol O-acyltransferase11q13.5 NM_001253891; 2 NM_032564; ENST00000228027; ENST00000376262; BC015234; uc001oxa.3; uc001oxb.3; ENST00000525545 RPRD1A -1.32 0.0287 0.6195 regulation of nuclear18q12.2 pre-mRNANM_018170; domain containing ENST00000357384; 1A ENST00000399022; AK292907; BC000225; BC010136; OTTHUMT00000255802; uc002kze.1; uc002kzg.3; uc010dmw.3; uc010dmx.3; ENST00000319040; ENST00000337059 1.49 0.0288 0.6199 ENST00000384449 SLC23A2 -1.32 0.029 0.6209 solute carrier family20p13 23 (ascorbicNM_005116; acid transporter), NM_203327; member ENST00000338244; 2 ENST00000379333; ENST00000468355; AK296304; BC013112; DQ011866; OTTHUMT00000077832; OTTHUMT00000077833; OTTHUMT00000077834; OTTHUMT00000077835; OTTHUMT00000077836; uc002wlg.1; uc002wlh.1; uc002wli.3; uc002wlj.1; uc010zqr.1; ENST00000424750 -1.36 0.0291 0.6218 DQ595182; uc004alk.1; uc004alk.2 MIR4635 1.31 0.0294 0.6247 microRNA 4635 NR_039778; uc021xvy.1 -1.68 0.0294 0.6247 ENST00000358469 1.34 0.0294 0.6247 ENST00000463255; OTTHUMT00000356953 KRTAP5-8 1.49 0.0295 0.6254 keratin associated11q13.4 protein 5-8NM_021046; ENST00000398534; OTTHUMT00000127954; uc001oqr.1 -1.34 0.0299 0.6294 ENST00000516409 1.35 0.03 0.6298 ENST00000408277 ATP2B3 -1.51 0.0302 0.6312 ATPase, Ca++ transporting,Xq28 plasmaNM_001001344; membrane NM_021949; 3 ENST00000263519; ENST00000349466; ENST00000359149; ENST00000370186; ENST00000393842; ENST00000460549; AK307765; BC130009; DQ201779; OTTHUMT00000060956; OTTHUMT00000060957; OTTHUMT00000060958; OTTHUMT00000060959; OTTHUMT00000060960; OTTHUMT00000354682; uc004fhs.1; uc004fht.1; uc004fhu.1; uc010nuf.1; ENST00000370181 C22orf39; HIRA -1.31 0.0302 0.6312 chromosome 2222q11.21 open readingNM_001166242; frame 39; histone NM_003325; cell cycle regulator NM_173793; ENST00000263208; ENST00000333059; ENST00000340170; ENST00000399562; ENST00000399568; ENST00000464189; ENST00000542103; AK289809; AK299950; AK302835; BC039835; BC062599; BX648073; OTTHUMT00000316488; OTTHUMT00000316489; OTTHUMT00000316494; OTTHUMT00000316495; OTTHUMT00000316499; OTTHUMT00000334594; OTTHUMT00000367691; uc002zpf.1; uc002zpi.3; uc002zpk.2; uc010grn.1; uc010gro.2; uc010grp.3; uc011agx.1; X75296; ENST00000539600; ENST00000541063; ENST00000546308; uc002zpj.2 CYP4F22 -1.37 0.0303 0.6316 cytochrome P450,19p13.12 family 4, subfamilyNM_173483; F, polypeptide ENST00000269703; 22 BC069351; BC093894; uc002nbh.4 1.36 0.0303 0.6316 uc021ptt.1 LINC00632 -1.38 0.0304 0.6316 long intergenicXq27.1 non-protein codingNR_028344; RNA 632 NR_028345; ENST00000370535; ENST00000498732; OTTHUMT00000058581; OTTHUMT00000058582; uc004fbe.2 1.44 0.0306 0.632 ENST00000365625 GDF11 -1.72 0.0308 0.6329 growth differentiation12q13.2 factorNM_005811; 11 ENST00000257868; uc001shq.3 MIR518A2 1.51 0.0308 0.6329 microRNA 518a-219q13.42 NR_030213; ENST00000384966; uc021vaq.1 -1.48 0.0309 0.6339 ENST00000363964 1.32 0.031 0.6342 ENST00000452971; OTTHUMT00000001204 1.62 0.0311 0.6342 DQ576083; uc002gtg.1 1.34 0.0314 0.6342 ENST00000413339; OTTHUMT00000046501 -1.52 0.0314 0.6342 ENST00000384020 -1.42 0.032 0.6342 ENST00000365350 CTH 1.36 0.0321 0.6342 cystathionine gamma-lyase1p31.1 NM_001190463; NM_001902; NM_153742; ENST00000346806; ENST00000370938; ENST00000411986; ENST00000464926; AK310269; BC015807; OTTHUMT00000025918; OTTHUMT00000025919; OTTHUMT00000025920; OTTHUMT00000025921; uc001dfd.3; uc001dfe.3; uc009wbl.2; uc010oqq.2 DCDC2 -1.31 0.0321 0.6342 doublecortin domain6p22.1 containingNM_001195610; 2 NM_016356; ENST00000378450; ENST00000378454; AL133043; BC050704; OTTHUMT00000043604; OTTHUMT00000043605; OTTHUMT00000043606; uc003ndw.3; uc003ndx.3; uc003ndy.3; ENST00000451359 MIR548AA2 -1.62 0.0321 0.6342 microRNA 548aa-2 NR_037517; uc021tfd.1 -1.66 0.0321 0.6342 DQ582939; uc021sez.1 -1.66 0.0321 0.6342 DQ582939; uc021sfm.1 -1.66 0.0321 0.6342 DQ582939; uc021sfj.1 -1.66 0.0321 0.6342 DQ582939; uc021sgr.1 -1.66 0.0321 0.6342 DQ582939; uc010ubo.1 -1.66 0.0321 0.6342 DQ582939; uc021siu.1 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by-1.66 peer review) is0.0321 the author/funder.0.6342 All rights reserved. No reuse allowed withoutDQ582939; permission. uc010uch.1 -1.66 0.0321 0.6342 DQ582939; uc021sgu.1 -1.66 0.0321 0.6342 DQ582939; uc021shb.1 -1.66 0.0321 0.6342 DQ582939; uc021shv.1 -1.66 0.0321 0.6342 DQ582939; uc002bba.1 MIR521-1 -1.35 0.0323 0.6342 microRNA 521-119q13.42 NR_030216; ENST00000384902; uc021vas.1 1.32 0.0325 0.6356 DQ578258; uc002ccx.2; uc002ccx.3 INE1 -1.4 0.0328 0.6379 inactivation escapeXp11.4-p11.3 1 (non-proteinNR_024616; coding) ENST00000456273; OTTHUMT00000107269; uc004dhl.3; uc004dhl.2 1.77 0.0328 0.6376 DQ590668; uc011afg.1; uc011afg.2 TRIM2 -1.42 0.0329 0.6383 tripartite motif4q31.3 containing 2 NM_001130067; NM_015271; ENST00000338700; ENST00000437508; ENST00000494872; BC011052; BC025417; OTTHUMT00000342649; OTTHUMT00000342650; OTTHUMT00000342652; OTTHUMT00000342667; OTTHUMT00000342668; OTTHUMT00000342669; OTTHUMT00000342670; OTTHUMT00000342671; OTTHUMT00000342672; OTTHUMT00000342673; OTTHUMT00000365202; uc003ing.2; uc003inh.2; uc003ini.1 -1.42 0.033 0.6386 uc021yau.1 1.35 0.0331 0.6386 ENST00000384597; uc021ptn.1 MIR1278 -1.38 0.0333 0.6403 microRNA 1278 NR_031691; ENST00000408753; uc021pgq.1 R3HCC1 -1.47 0.0333 0.6403 R3H domain and8p21.3 coiled-coil containingNM_001136108; 1 ENST00000265806; ENST00000411463; ENST00000522012; ENST00000523720; BC128546; BC143822; BC143829; OTTHUMT00000375464; OTTHUMT00000375465; OTTHUMT00000375466; OTTHUMT00000375467; OTTHUMT00000375468; OTTHUMT00000375469; OTTHUMT00000375470; OTTHUMT00000375471; OTTHUMT00000375472; uc003xdf.3; uc011kzt.2; ENST00000518454; uc003xdg.1 -2.41 0.0334 0.6406 DQ575002; uc002aau.1 STRA13 -1.58 0.0335 0.6406 stimulated by retinoic17q25.3 acid 13NM_144998; ENST00000306704; ENST00000392359; BC009571; OTTHUMT00000255173; OTTHUMT00000255174; U95007; uc002kdc.3; uc002kdd.3 1.33 0.0335 0.6406 ENST00000526642 1.46 0.0336 0.6409 DQ589620; uc021uhp.1 1.48 0.0339 0.6413 uc021vsw.1 -1.36 0.034 0.6413 ENST00000458443; OTTHUMT00000098808 CTD-2653M23.2 -1.35 0.034 0.6413 OTTHUMT00000366970; ENST00000501714 SRPR -1.43 0.0341 0.6413 signal recognition11q24.2 particle receptorNM_001177842; (docking protein) NM_003139; ENST00000332118; ENST00000530680; ENST00000532259; BC001162; BC009110; BC013583; uc001qdh.3; uc010sbm.2 -1.38 0.0341 0.6413 DQ579654; uc021yxh.1 1.3 0.0342 0.6413 DQ579765; uc002ahz.2; uc002ahz.3 1.33 0.0342 0.6413 ENST00000415746; OTTHUMT00000048530 GPR156 -1.38 0.0344 0.6413 G protein-coupled3q13.33 receptor 156NM_001168271; NM_153002; ENST00000315843; ENST00000461057; ENST00000464295; BC113701; BC143606; OTTHUMT00000355138; OTTHUMT00000355139; OTTHUMT00000355140; OTTHUMT00000355141; uc011bjf.2; uc011bjg.2 1.37 0.0344 0.6415 ENST00000363116 MIR4316 1.3 0.0346 0.642 microRNA 4316 NR_036200; uc021udy.1 1.32 0.0346 0.642 DQ574970; uc002nwu.1 SNORA3B 1.31 0.0347 0.642 small nucleolar11p15.4 RNA, H/ACA boxNR_002977; 3B ENST00000391305; uc001mgr.1 RGL1 -1.35 0.0348 0.642 ral guanine nucleotide1q25.3 dissociationNM_015149; stimulator-like ENST00000304685; 1 ENST00000360851; AK295179; AK295611; AK304293; AK316526; BC136591; OTTHUMT00000085481; OTTHUMT00000085742; uc001gqm.3; uc010pof.1; uc010pog.2; uc010poh.2; uc010poi.2; ENST00000367531; ENST00000536277; ENST00000539189; ENST00000543395; uc001gqo.3 -1.45 0.0348 0.642 DQ572638; uc021yxv.1 -1.38 0.0348 0.642 ENST00000362545 1.57 0.0349 0.642 DQ586641; uc002kpf.2; uc002kpf.3 1.52 0.035 0.642 DQ577682; uc002ahk.2; uc002ahk.3 TRGV5 -1.31 0.0351 0.642 T cell receptor 7p14gamma variableOTTHUMT00000338407; 5 Y00482; ENST00000390344; uc022aca.1 LOC100287036 1.34 0.0352 0.642 uncharacterized16q24.3 LOC100287036NM_001242885; uc010vpi.2; uc010vpi.1 1.66 0.0353 0.6421 DQ588796; uc021uqa.1 1.67 0.0353 0.6421 ENST00000384475 MARCKS 1.4 0.0354 0.6428 myristoylated 6q22.2alanine-rich proteinNM_002356; kinase C BC089040; substrate uc003pvy.4; ENST00000368635; OTTHUMT00000041903 -1.31 0.0355 0.6436 ENST00000517057 1.35 0.0356 0.6437 DQ586930; uc021soh.1 KRTAP21-3 1.32 0.0359 0.6465 keratin associated21q22.11 protein 21-3NM_001164435; ENST00000444335; OTTHUMT00000246864; uc021wii.1 OPA1-AS1 1.38 0.036 0.6467 OPA1 antisense RNA 1 ENST00000433105; ENST00000444085; OTTHUMT00000342927; OTTHUMT00000342928 -1.32 0.0362 0.6467 ENST00000443838; OTTHUMT00000051772 1.36 0.0363 0.6467 ENST00000529323 1.38 0.0365 0.648 ENST00000425322; OTTHUMT00000326062 1.32 0.0365 0.648 7SK; uc021snk.1 -1.34 0.0365 0.648 ENST00000516302 -1.43 0.0365 0.648 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by1.33 peer review) is0.0368 the author/funder.0.6484 All rights reserved. No reuse allowed withoutENST00000516510 permission. 1.32 0.0368 0.6482 uc021yho.1 1.49 0.037 0.6496 DQ600036; uc021snz.1 ELMOD1 1.36 0.0372 0.6501 ELMO/CED-12 11q22.3domain containingENST00000529675; 1 NR_028328; uc001pjo.1 1.32 0.0375 0.6508 ENST00000534169 1.42 0.0376 0.6516 uc021oxo.1 -1.32 0.0376 0.6516 ENST00000527398 -1.31 0.0379 0.6539 ENST00000458815 2.4 0.0379 0.6537 DQ591177; uc021rxw.1 1.32 0.038 0.6542 ENST00000508766; OTTHUMT00000370935 1.4 0.0383 0.655 uc022bwm.1 -1.37 0.0383 0.655 ENST00000514840; OTTHUMT00000370383 1.31 0.0384 0.655 ENST00000558710 -1.32 0.0386 0.6556 uc021vgs.1 HOXB13 -1.51 0.0387 0.6556 homeobox B1317q21.2 NM_006361; ENST00000290295; BC007092; BC070233; OTTHUMT00000358087; uc002ioa.3 1.3 0.0387 0.6556 ENST00000384648 1.67 0.0387 0.6556 DQ573937; uc010twb.1; uc010twb.2 ARF5 -1.3 0.0391 0.6565 ADP-ribosylation7q31.3 factor 5 NM_001662; ENST00000000233; ENST00000467281; AK307297; BC003043; BC033104; OTTHUMT00000059567; OTTHUMT00000141971; OTTHUMT00000141972; OTTHUMT00000141973; OTTHUMT00000308979; OTTHUMT00000317141; uc003vmb.2; uc010llb.2; OTTHUMT00000141974 1.56 0.0391 0.6565 ENST00000458880 -1.68 0.0392 0.6565 uc021xue.1 -1.74 0.0393 0.6565 DQ592342; uc021qur.1 1.36 0.0394 0.6566 DQ599155; uc004alq.1; uc004alq.2 1.34 0.0394 0.6565 ENST00000364580 -1.4 0.0395 0.657 ENST00000399242 -2.2 0.0398 0.658 ENST00000534271 SHISA2 -1.4 0.0405 0.6615 shisa family member13q12.13 2 NM_001007538; ENST00000319420; BC132898; OTTHUMT00000044239; uc001uqm.1 1.32 0.0405 0.6615 ENST00000499715; ENST00000514290; OTTHUMT00000360002; OTTHUMT00000360003 1.41 0.041 0.6631 DQ573760; uc021snq.1 -1.5 0.0412 0.6638 ENST00000439177 1.32 0.0413 0.6641 uc021oxy.1 IGHD2-15 -1.43 0.0414 0.6653 immunoglobulin14q32.33 heavy diversityOTTHUMT00000326208; 2-15 ENST00000390578 RNA5SP348 -1.43 0.0415 0.6654 RNA, 5S ribosomal pseudogeneENST00000516442 348 LOC101927869 -1.33 0.0417 0.6662 uncharacterized LOC101927869ENST00000416218; OTTHUMT00000171146 -1.52 0.0418 0.6675 ENST00000516061; uc021ukx.1 2.04 0.042 0.6677 ENST00000408631 AC079610.1 1.43 0.0422 0.6682 OTTHUMT00000337266; ENST00000426870 MIR3162 -1.33 0.0424 0.6684 microRNA 3162 NR_036120; uc021qjy.1 LOC105370832 1.34 0.0427 0.6684 uncharacterized LOC105370832BC037892; uc002ads.3 1.34 0.0427 0.6684 uc021vjo.1 1.4 0.043 0.6684 DQ593162; uc021ywt.1 OCLM 1.35 0.0431 0.6684 oculomedin 1q25 NM_022375; BC069096; BC093987; uc001gry.3 1.38 0.0431 0.6684 ENST00000363474 -2.11 0.0433 0.6684 DQ575342; uc021rxp.1 KLHDC10 -1.3 0.0435 0.6684 kelch domain containing7q32.2 10 NM_014997; ENST00000335420; ENST00000495724; BC009977; BC036464; BC044884; D87454; OTTHUMT00000349347; OTTHUMT00000349349; OTTHUMT00000349350; OTTHUMT00000349351; uc003vpj.2; uc003vpk.2; uc010lmb.2 1.37 0.0435 0.6684 ENST00000401112 HLA-DMA -1.3 0.0439 0.6684 major histocompatibility6p21.3 complex,NM_006120; class II, DMAK298081; alpha BC011447; BC026279; OTTHUMT00000077020; OTTHUMT00000315163; OTTHUMT00000315164; OTTHUMT00000315165; OTTHUMT00000315166; OTTHUMT00000315167; OTTHUMT00000315168; OTTHUMT00000315169; OTTHUMT00000315170; OTTHUMT00000315171; uc011fov.1; uc011fow.1 HLA-DMA -1.3 0.0439 0.6684 major histocompatibility6p21.3 complex,NM_006120; class II, DMAK298081; alpha BC011447; BC026279; OTTHUMT00000311577; OTTHUMT00000311578; OTTHUMT00000311579; OTTHUMT00000311580; OTTHUMT00000311581; OTTHUMT00000311582; OTTHUMT00000311583; OTTHUMT00000311584; OTTHUMT00000311585; OTTHUMT00000311586; uc011hfo.1; uc011hfp.1 HLA-DMA -1.3 0.0439 0.6684 major histocompatibility6p21.3 complex,NM_006120; class II, DMAK298081; alpha BC011447; BC026279; OTTHUMT00000312660; OTTHUMT00000312661; OTTHUMT00000312662; OTTHUMT00000312663; OTTHUMT00000312664; OTTHUMT00000312665; OTTHUMT00000312666; OTTHUMT00000312667; OTTHUMT00000312668; OTTHUMT00000312669; uc011iax.1; uc011iay.1 HLA-DMA -1.3 0.0439 0.6684 major histocompatibility6p21.3 complex,NM_006120; class II, DMAK298081; alpha BC011447; BC026279; OTTHUMT00000035139; OTTHUMT00000314521; OTTHUMT00000314522; OTTHUMT00000314523; OTTHUMT00000314524; OTTHUMT00000314525; OTTHUMT00000314526; OTTHUMT00000314527; OTTHUMT00000314528; OTTHUMT00000314529; uc011iyh.1; uc011iyi.1 HLA-DMA -1.3 0.0439 0.6684 major histocompatibility6p21.3 complex,NM_006120; class II, DMAK298081; alpha BC011447; BC026279; OTTHUMT00000276565; OTTHUMT00000315643; OTTHUMT00000315644; OTTHUMT00000315645; OTTHUMT00000315646; OTTHUMT00000315647; OTTHUMT00000315648; OTTHUMT00000315649; OTTHUMT00000315650; OTTHUMT00000315651; uc011jtr.1; uc011jts.1 bioRxiv preprint doi: https://doi.org/10.1101/589648; this version posted March 27, 2019. The copyright holder for this preprint (which was not certified by-1.44 peer review) is0.0439 the author/funder.0.6684 All rights reserved. No reuse allowed withoutENST00000515960; permission. uc021sch.1 ZFP69B -1.31 0.0443 0.6684 ZFP69 zinc finger1p34.2 protein B NM_023070; ENST00000361584; ENST00000411995; ENST00000484445; AL137241; BC017498; OTTHUMT00000019078; OTTHUMT00000019079; OTTHUMT00000019080; uc001cfl.2; uc001cfn.2; ENST00000431552; uc001cfm.2 1.6 0.0444 0.6684 DQ577649; uc010rfx.1 MIR3613 1.57 0.0448 0.6702 microRNA 3613 NR_037407; uc021rjp.1 -1.37 0.0448 0.6705 ENST00000419211; OTTHUMT00000340907 ANXA6 -1.39 0.0453 0.6706 annexin A6 5q33.1 NM_001155; NM_001193544; ENST00000354546; ENST00000377751; ENST00000519610; ENST00000521512; ENST00000523714; AK130077; BC017046; OTTHUMT00000377668; OTTHUMT00000377669; OTTHUMT00000377670; OTTHUMT00000377671; OTTHUMT00000377706; OTTHUMT00000377707; OTTHUMT00000377708; OTTHUMT00000377709; OTTHUMT00000377741; OTTHUMT00000377742; OTTHUMT00000377743; OTTHUMT00000377744; OTTHUMT00000377745; OTTHUMT00000377746; OTTHUMT00000377747; uc003ltl.2; uc003lto.2; uc011dcp.2; ENST00000356496; ENST00000540153 MIR4748 1.41 0.0454 0.6706 microRNA 4748 NR_039903; uc021upa.1 1.36 0.0455 0.6708 ENST00000364943; uc021vuh.1 1.37 0.0455 0.6708 ENST00000431394; ENST00000454135; OTTHUMT00000040879; OTTHUMT00000040880 1.34 0.0456 0.6708 ENST00000458885 -1.31 0.0456 0.6708 OTTHUMT00000347221 PCDH9-AS3 -1.34 0.0457 0.6708 PCDH9 antisense RNA 3 ENST00000434073; OTTHUMT00000045212 MRPL54 -1.41 0.0458 0.6708 mitochondrial 19p13.3ribosomal proteinNM_172251; L54 ENST00000330133; BC065273; uc002lyq.4 1.51 0.0458 0.6708 ENST00000408075 1.94 0.046 0.671 DQ586004; uc021trw.1 1.94 0.046 0.671 DQ577610; uc002gxe.2 -1.45 0.046 0.6711 BC137370; BC137374; uc001zhb.2 -1.35 0.0461 0.6716 ENST00000422418 HACD2 -1.34 0.0462 0.6719 3-hydroxyacyl-CoA3q21.1 dehydrataseENST00000471236; 2 OTTHUMT00000356075 -1.34 0.0464 0.6729 ENST00000451755; OTTHUMT00000324427 1.47 0.0466 0.6729 DQ586142; uc010vzs.1; uc010vzs.2 3.49 0.0466 0.6729 ENST00000517235 1.52 0.0466 0.6729 DQ593554; uc011lrk.1 1.35 0.0469 0.6734 ENST00000459209 -1.31 0.0469 0.6734 ENST00000516823 ALDH1L2 1.46 0.0471 0.6745 aldehyde dehydrogenase12q23.3 1 family,NM_001034173; member L2 NR_027752; ENST00000258494; BC103934; BC103935; CR627287; uc001tlc.3; uc009zuo.3; uc009zup.3; ENST00000424857 1.58 0.0472 0.675 DQ588253; uc002aac.2 MIR505 -1.48 0.0473 0.6753 microRNA 505Xq27.1 NR_030230; uc022cfe.1; ENST00000384901 -1.42 0.0474 0.6753 ENST00000362724; uc021wve.1 1.53 0.0474 0.676 ENST00000526310 1.41 0.0478 0.6778 ENST00000391270 2.76 0.0481 0.6791 DQ597999; uc021uvd.1 MIR4795 -1.31 0.0483 0.6794 microRNA 4795 NR_039958; uc021xbb.1 -1.44 0.0484 0.6801 ENST00000365620 1.41 0.049 0.6835 DQ601762; uc003asl.1 -1.54 0.049 0.6835 ENST00000391023 1.33 0.0491 0.6835 ENST00000363997; 7SK MYO10 -1.33 0.0492 0.6835 myosin X 5p15.1 NM_012334; ENST00000274203; ENST00000505695; ENST00000507288; ENST00000512061; ENST00000513610; ENST00000515803; AK295630; AK295736; AK303459; AK316138; AL832428; BC041694; BC094838; BC137168; BC150285; OTTHUMT00000366167; OTTHUMT00000366168; OTTHUMT00000366169; OTTHUMT00000366170; OTTHUMT00000366171; OTTHUMT00000366172; OTTHUMT00000366173; OTTHUMT00000366174; OTTHUMT00000366175; OTTHUMT00000366176; OTTHUMT00000366177; uc003jft.4; uc003jfu.2; uc003jfv.2; uc010itx.3; uc011cnb.2; uc011cnc.2; uc011cnd.2; uc011cne.2; ENST00000427430 1.38 0.0493 0.6835 ENST00000458261; OTTHUMT00000054069 SCARNA9L 1.31 0.0494 0.6839 small Cajal body-specificXp22.12 RNANR_023358; 9-like uc010nfp.3; ENST00000364722; ENST00000365012 BMS1P18; BMS1P17 1.32 0.0498 0.6844 BMS1 ribosome14q11.2 biogenesis factorBC040855; pseudogene ENST00000440946; 18; BMS1 ribosome uc002zkt.3 biogenesis factor pseudogene 17