PreprintCited by 1,122Genomics and Chromatin DynamicsGene Regulatory Network AnalysisBioinformatics and Genomic Networks

Benchmark and integration of resources for the estimation of human transcription factor activities

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Luz García‐Alonso, Christian H. Holland, Mahmoud M. Ibrahim, Dénes Türei, Julio Sáez-Rodríguez·2019·Genome Research

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Abstract

The prediction of transcription factor (TF) activities from the gene expression of their targets (i.e., TF regulon) is becoming a widely used approach to characterize the functional status of transcriptional regulatory circuits. Several strategies and data sets have been proposed to link the target genes likely regulated by a TF, each one providing a different level of evidence. The most established ones are (1) manually curated repositories, (2) interactions derived from ChIP-seq binding data, (3) in silico prediction of TF binding on gene promoters, and (4) reverse-engineered regulons from large gene expression data sets. However, it is not known how these different sources of regulons affect the TF activity estimations and, thereby, downstream analysis and interpretation. Here we compared the accuracy and biases of these strategies to define human TF regulons by means of their ability to predict changes in TF activities in three reference benchmark data sets. We assembled a collection of TF–target interactions for 1541 human TFs and evaluated how different molecular and regulatory properties of the TFs, such as the DNA-binding domain, specificities, or mode of interaction with the chromatin, affect the predictions of TF activity. We assessed their coverage and found little overlap on the regulons derived from each strategy and better performance by literature-curated information followed by ChIP-seq data. We provide an integrated resource of all TF–target interactions derived through these strategies, with confidence scores, as a resource for enhanced prediction of TF activities.

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  1. Alvarez MJ, Shen Y, Giorgi FM, Lachmann A, Ding BB, Ye BH, Califano A. 2016 Functional characterization of somatic mutations in cancer using network-based inference of protein activity. Nat Genet 48: 838– 847. 10.1038/ng.3593 27322546 PMC5040167 · DOI · Paper page
  2. Bailey TL, Johnson J, Grant CE, Noble WS. 2015 The MEME Suite. Nucleic Acids Res 43: W39– W49. 10.1093/nar/gkv416 25953851 PMC4489269 · DOI
  3. Bleda M, Tarraga J, de Maria A, Salavert F, Garcia-Alonso L, Celma M, Martin A, Dopazo J, Medina I. 2012 CellBase, a comprehensive collection of RESTful web services for retrieving relevant biological information from heterogeneous sources. Nucleic Acids Res 40: W609– W614. 10.1093/nar/gks575 22693220 PMC3394301 · DOI
  4. Boros J, Donaldson IJ, O'Donnell A, Odrowaz ZA, Zeef L, Lupien M, Meyer CA, Liu XS, Brown M, Sharrocks AD. 2009 Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machinery. Genome Res 19: 1963– 1973. 10.1101/gr.093047.109 19687146 PMC2775591 · DOI · Paper page
  5. Bovolenta LA, Acencio ML, Lemke N. 2012 HTRIdb: an open-access database for experimentally verified human transcriptional regulation interactions. BMC Genomics 13: 405 10.1186/1471-2164-13-405 22900683 PMC3472291 · DOI
  6. Cantini L, Calzone L, Martignetti L, Rydenfelt M, Blüthgen N, Barillot E, Zinovyev A. 2018 Classification of gene signatures for their information value and functional redundancy. NPJ Syst Biol Appl 4: 2 10.1038/s41540-017-0038-8 29263798 PMC5736638 · DOI
  7. Carithers LJ, Ardlie K, Barcus M, Branton PA, Britton A, Buia SA, Compton CC, DeLuca DS, Peter-Demchok J, Gelfand ET, 2015 A novel approach to high-quality postmortem tissue procurement: the GTEx project. Biopreserv Biobank 13: 311– 319. 10.1089/bio.2015.0032 26484571 PMC4675181 · DOI · Paper page
  8. Carro MS, Lim WK, Alvarez MJ, Bollo RJ, Zhao X, Snyder EY, Sulman EP, Anne SL, Doetsch F, Colman H, 2010 The transcriptional network for mesenchymal transformation of brain tumours. Nature 463: 318– 325. 10.1038/nature08712 20032975 PMC4011561 · DOI
  9. Chan SC, Selth LA, Li Y, Nyquist MD, Miao L, Bradner JE, Raj GV, Tilley WD, Dehm SM. 2015 Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Res 43: 5880– 5897. 10.1093/nar/gkv262 25908785 PMC4499120 · DOI
  10. Chèneby J, Gheorghe M, Artufel M, Mathelier A, Ballester B. 2018 ReMap 2018: an updated atlas of regulatory regions from an integrative analysis of DNA-binding ChIP-seq experiments. Nucleic Acids Res 46: D267– D275. 10.1093/nar/gkx1092 29126285 PMC5753247 · DOI
  11. Clarke DJB, Kuleshov MV, Schilder BM, Torre D, Duffy ME, Keenan AB, Lachmann A, Feldmann AS, Gundersen GW, Silverstein MC, 2018 eXpression2Kinases (X2K) Web: linking expression signatures to upstream cell signaling networks. Nucleic Acids Res 46: W171– W179. 10.1093/nar/gky458 29800326 PMC6030863 · DOI
  12. Crawford GE, Holt IE, Whittle J, Webb BD, Tai D, Davis S, Margulies EH, Chen Y, Bernat JA, Ginsburg D, 2006 Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS). Genome Res 16: 123– 131. 10.1101/gr.4074106 16344561 PMC1356136 · DOI
  13. Ding H, Douglass EF Jr, Sonabend AM, Mela A, Bose S, Gonzalez C, Canoll PD, Sims PA, Alvarez MJ, Califano A. 2018 Quantitative assessment of protein activity in orphan tissues and single cells using the metaVIPER algorithm. Nat Commun 9: 1471 10.1038/s41467-018-03843-3 29662057 PMC5902599 · DOI
  14. Ehsani R, Bahrami S, Drabløs F. 2016 Feature-based classification of human transcription factors into hypothetical sub-classes related to regulatory function. BMC Bioinformatics 17: 459 10.1186/s12859-016-1349-2 27842491 PMC5109715 · DOI
  15. Essaghir A, Toffalini F, Knoops L, Kallin A, van Helden J, Demoulin J-B. 2010 Transcription factor regulation can be accurately predicted from the presence of target gene signatures in microarray gene expression data. Nucleic Acids Res 38: e120 10.1093/nar/gkq149 20215436 PMC2887972 · DOI
  16. Falco MM, Bleda M, Carbonell-Caballero J, Dopazo J. 2016 The pan-cancer pathological regulatory landscape. Sci Rep 6: 36709 10.1038/srep39709 28000771 PMC5175166 · DOI
  17. Farnham PJ. 2009 Insights from genomic profiling of transcription factors. Nat Rev Genet 10: 605– 616. 10.1038/nrg2636 19668247 PMC2846386 · DOI · Paper page
  18. Fisher WW, Li JJ, Hammonds AS, Brown JB, Pfeiffer BD, Weiszmann R, MacArthur S, Thomas S, Stamatoyannopoulos JA, Eisen MB, 2012 DNA regions bound at low occupancy by transcription factors do not drive patterned reporter gene expression in Drosophila. Proc Natl Acad Sci 109: 21330– 21335. 10.1073/pnas.1209589110 23236164 PMC3535648 · DOI
  19. Garcia-Alonso L, Iorio F, Matchan A, Fonseca N, Jaaks P, Peat G, Pignatelli M, Falcone F, Benes CH, Dunham I, 2018 Transcription factor activities enhance markers of drug sensitivity in cancer. Cancer Res 78: 769– 780. 10.1158/0008-5472.CAN-17-1679 29229604 PMC6522379 · DOI
  20. Gonzalez-Perez A. 2016 Circuits of cancer drivers revealed by convergent misregulation of transcription factor targets across tumor types. Genome Med 8: 6 10.1186/s13073-015-0260-1 26792175 PMC4719577 · DOI
  21. Grant CE, Bailey TL, Noble WS. 2011 FIMO: scanning for occurrences of a given motif. Bioinformatics 27: 1017– 1018. 10.1093/bioinformatics/btr064 21330290 PMC3065696 · DOI · Paper page
  22. Grau J, Grosse I, Keilwagen J. 2015 PRROC: computing and visualizing precision-recall and receiver operating characteristic curves in R. Bioinformatics 31: 2595– 2597. 10.1093/bioinformatics/btv153 25810428 PMC4514923 · DOI
  23. Gronostajski RM, Guaneri J, Lee DH, Gallo SM. 2011 The NFI-Regulome Database: a tool for annotation and analysis of control regions of genes regulated by Nuclear Factor I transcription factors. J Clin Bioinforma 1: 4 10.1186/2043-9113-1-4 21884625 PMC3143897 · DOI
  24. Han H, Cho J-W, Lee S, Yun A, Kim H, Bae D, Yang S, Kim CY, Lee M, Kim E, 2018 TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions. Nucleic Acids Res 46: D380– D386. 10.1093/nar/gkx1013 29087512 PMC5753191 · DOI
  25. Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, Aken BL, Barrell D, Zadissa A, Searle S, 2012 GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res 22: 1760– 1774. 10.1101/gr.135350.111 22955987 PMC3431492 · DOI · Paper page
  26. Iorio F, Knijnenburg TA, Vis DJ, Bignell GR, Menden MP, Schubert M, Aben N, Gonçalves E, Barthorpe S, Lightfoot H, 2016 A landscape of pharmacogenomic interactions in cancer. Cell 166: 740– 754. 10.1016/j.cell.2016.06.017 27397505 PMC4967469 · DOI · Paper page
  27. Jiang C, Xuan Z, Zhao F, Zhang MQ. 2007 TRED: a transcriptional regulatory element database, new entries and other development. Nucleic Acids Res 35: D137– D140. 10.1093/nar/gkl1041 17202159 PMC1899102 · DOI
  28. Johnson DS, Mortazavi A, Myers RM, Wold B. 2007 Genome-wide mapping of in vivo protein-DNA interactions. Science 316: 1497– 1502. 10.1126/science.1141319 17540862 · DOI · Paper page
  29. Kanehisa M, Goto S, Sato Y, Furumichi M, Tanabe M. 2012 KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res 40: D109– D114. 10.1093/nar/gkr988 22080510 PMC3245020 · DOI · Paper page
  30. Kawaji H, Severin J, Lizio M, Forrest ARR, van Nimwegen E, Rehli M, Schroder K, Irvine K, Suzuki H, Carninci P, 2011 Update of the FANTOM web resource: from mammalian transcriptional landscape to its dynamic regulation. Nucleic Acids Res 39: D856– D860. 10.1093/nar/gkq1112 21075797 PMC3013704 · DOI
  31. Khan A, Fornes O, Stigliani A, Gheorghe M, Castro-Mondragon JA, van der Lee R, Bessy A, Chèneby J, Kulkarni SR, Tan G, 2018 JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework. Nucleic Acids Res 46: D260– D266. 10.1093/nar/gkx1126 29140473 PMC5753243 · DOI
  32. Klijn C, Durinck S, Stawiski EW, Haverty PM, Jiang Z, Liu H, Degenhardt J, Mayba O, Gnad F, Liu J, 2015 A comprehensive transcriptional portrait of human cancer cell lines. Nat Biotechnol 33: 306– 312. 10.1038/nbt.3080 25485619 · DOI
  33. Kolchanov NA, Ignatieva EV, Ananko EA, Podkolodnaya OA, Stepanenko IL, Merkulova TI, Pozdnyakov MA, Podkolodny NL, Naumochkin AN, Romashchenko AG. 2002 Transcription Regulatory Regions Database (TRRD): its status in 2002. Nucleic Acids Res 30: 312– 317. 10.1093/nar/30.1.312 11752324 PMC99088 · DOI
  34. Kulakovskiy IV, Vorontsov IE, Yevshin IS, Sharipov RN, Fedorova AD, Rumynskiy EI, Medvedeva YA, Magana-Mora A, Bajic VB, Papatsenko DA, et al. 2018 HOCOMOCO: towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis. Nucleic Acids Res 46: D252– D259. 10.1093/nar/gkx1106 29140464 PMC5753240 · DOI
  35. Lachmann A, Xu H, Krishnan J, Berger SI, Mazloom AR, Ma'ayan A. 2010 ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments. Bioinformatics 26: 2438– 2444. 10.1093/bioinformatics/btq466 20709693 PMC2944209 · DOI
  36. Leek JT, Johnson WE, Parker HS, Jaffe AE, Storey JD. 2012 The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics 28: 882– 883. 10.1093/bioinformatics/bts034 22257669 PMC3307112 · DOI · Paper page
  37. Lesurf R, Cotto KC, Wang G, Griffith M, Kasaian K, Jones SJM, Montgomery SB, Griffith OL, Open Regulatory Annotation Consortium. 2016 ORegAnno 3.0: a community-driven resource for curated regulatory annotation. Nucleic Acids Res 44: D126– D132. 10.1093/nar/gkv1203 26578589 PMC4702855 · DOI · Paper page
  38. Lex A, Gehlenborg N. 2014 Sets and intersections. Nat Methods 11: 779 10.1038/nmeth.3033 25825831 · DOI
  39. Li X-Y, MacArthur S, Bourgon R, Nix D, Pollard DA, Iyer VN, Hechmer A, Simirenko L, Stapleton M, Luengo Hendriks CL, 2008 Transcription factors bind thousands of active and inactive regions in the Drosophila blastoderm. PLoS Biol 6: e27 10.1371/journal.pbio.0060027 18271625 PMC2235902 · DOI
  40. Liu ZP, Wu C, Miao H, Wu H. 2015 RegNetwork: an integrated database of transcriptional and post-transcriptional regulatory networks in human and mouse. Database (Oxford) 2015: bav095. 10.1093/database/bav095 26424082 PMC4589691 · DOI
  41. Marbach D, Prill RJ, Schaffter T, Mattiussi C, Floreano D, Stolovitzky G. 2010 Revealing strengths and weaknesses of methods for gene network inference. Proc Natl Acad Sci 107: 6286– 6291. 10.1073/pnas.0913357107 20308593 PMC2851985 · DOI
  42. Marbach D, Costello JC, Küffner R, Vega NM, Prill RJ, Camacho DM, Allison KR, DREAM5 Consortium, Kellis M, Collins JJ, 2012 Wisdom of crowds for robust gene network inference. Nat Methods 9: 796– 804. 10.1038/nmeth.2016 22796662 PMC3512113 · DOI · Paper page
  43. Margolin AA, Califano A. 2007 Theory and limitations of genetic network inference from microarray data. Ann N Y Acad Sci 1115: 51– 72. 10.1196/annals.1407.019 17925348 · DOI
  44. Margolin AA, Wang K, Lim WK, Kustagi M, Nemenman I, Califano A. 2006 Reverse engineering cellular networks. Nat Protoc 1: 662– 671. 10.1038/nprot.2006.106 17406294 · DOI · Paper page
  45. McDonald ER III, de Weck A, Schlabach MR, Billy E, Mavrakis KJ, Hoffman GR, Belur D, Castelletti D, Frias E, Gampa K, 2017 Project DRIVE: a compendium of cancer dependencies and synthetic lethal relationships uncovered by large-scale, deep RNAi screening. Cell 170: 577– 592.e10. 10.1016/j.cell.2017.07.005 28753431 · DOI · Paper page
  46. Melas IN, Sakellaropoulos T, Iorio F, Alexopoulos LG, Loh W-Y, Lauffenburger DA, Saez-Rodriguez J, Bai JPF. 2015 Identification of drug-specific pathways based on gene expression data: application to drug induced lung injury. Integr Biol (Camb) 7: 904– 920. 10.1039/c4ib00294f 25932872 · DOI
  47. Orchard S, Ammari M, Aranda B, Breuza L, Briganti L, Broackes-Carter F, Campbell NH, Chavali G, Chen C, del-Toro N, 2014 The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases. Nucleic Acids Res 42: D358– D363. 10.1093/nar/gkt1115 24234451 PMC3965093 · DOI
  48. Osmanbeyoglu HU, Toska E, Chan C, Baselga J, Leslie CS. 2017 Pancancer modelling predicts the context-specific impact of somatic mutations on transcriptional programs. Nat Commun 8: 14249 10.1038/ncomms14249 28139702 PMC5290314 · DOI
  49. Ouyang Z, Zhou Q, Wong WH. 2009 ChIP-Seq of transcription factors predicts absolute and differential gene expression in embryonic stem cells. Proc Natl Acad Sci 106: 21521– 21526. 10.1073/pnas.0904863106 19995984 PMC2789751 · DOI
  50. Petryszak R, Burdett T, Fiorelli B, Fonseca NA, Gonzalez-Porta M, Hastings E, Huber W, Jupp S, Keays M, Kryvych N, 2014 Expression Atlas update—a database of gene and transcript expression from microarray- and sequencing-based functional genomics experiments. Nucleic Acids Res 42: D926– D932. 10.1093/nar/gkt1270 24304889 PMC3964963 · DOI
  51. Pollard KS, Hubisz MJ, Rosenbloom KR, Siepel A. 2010 Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res 20: 110– 121. 10.1101/gr.097857.109 19858363 PMC2798823 · DOI · Paper page
  52. Portales-Casamar E, Arenillas D, Lim J, Swanson MI, Jiang S, McCallum A, Kirov S, Wasserman WW. 2009 The PAZAR database of gene regulatory information coupled to the ORCA toolkit for the study of regulatory sequences. Nucleic Acids Res 37: D54– D60. 10.1093/nar/gkn783 18971253 PMC2686574 · DOI
  53. Rice JJ, Tu Y, Stolovitzky G. 2005 Reconstructing biological networks using conditional correlation analysis. Bioinformatics 21: 765– 773. 10.1093/bioinformatics/bti064 15486043 · DOI
  54. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK. 2015 limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43: e47. 10.1093/nar/gkv007 PMC4402510 25605792 · DOI · Paper page
  55. Robinson MD, McCarthy DJ, Smyth GK. 2010 edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26: 139– 140. 10.1093/bioinformatics/btp616 19910308 PMC2796818 · DOI · Paper page
  56. Schacht T, Oswald M, Eils R, Eichmüller SB, König R. 2014 Estimating the activity of transcription factors by the effect on their target genes. Bioinformatics 30: i401– i407. 10.1093/bioinformatics/btu446 25161226 PMC4147899 · DOI
  57. Schubert M, Klinger B, Klünemann M, Sieber A, Uhlitz F, Sauer S, Garnett MJ, Blüthgen N, Saez-Rodriguez J. 2018 Perturbation-response genes reveal signaling footprints in cancer gene expression. Nat Commun 9: 20 10.1038/s41467-017-02391-6 29295995 PMC5750219 · DOI
  58. Sinha S. 2006 On counting position weight matrix matches in a sequence, with application to discriminative motif finding. Bioinformatics 22: e454– e463. 10.1093/bioinformatics/btl227 16873507 · DOI
  59. Stormo GD. 2000 DNA binding sites: representation and discovery. Bioinformatics 16: 16– 23. 10.1093/bioinformatics/16.1.16 10812473 · DOI
  60. Tootle TL, Rebay I. 2005 Post-translational modifications influence transcription factor activity: a view from the ETS superfamily. Bioessays 27: 285– 298. 10.1002/bies.20198 15714552 · DOI
  61. Trescher S, Münchmeyer J, Leser U. 2017 Estimating genome-wide regulatory activity from multi-omics data sets using mathematical optimization. BMC Syst Biol 11: 41 10.1186/s12918-017-0419-z 28347313 PMC5369021 · DOI
  62. Tripathi S, Vercruysse S, Chawla K, Christie KR, Blake JA, Huntley RP, Orchard S, Hermjakob H, Thommesen L, Lægreid A, 2016 Gene regulation knowledge commons: community action takes care of DNA binding transcription factors. Database 2016: baw088 10.1093/database/baw088 27270715 PMC4911790 · DOI
  63. Tsherniak A, Vazquez F, Montgomery PG, Weir BA, Kryukov G, Cowley GS, Gill S, Harrington WF, Pantel S, Krill-Burger JM, 2017 Defining a cancer dependency map. Cell 170: 564– 576.e16. 10.1016/j.cell.2017.06.010 28753430 PMC5667678 · DOI · Paper page
  64. Tuncbag N, Gosline SJC, Kedaigle A, Soltis AR, Gitter A, Fraenkel E. 2016 Network-based interpretation of diverse high-throughput datasets through the Omics Integrator software package. PLoS Comput Biol 12: e1004879 10.1371/journal.pcbi.1004879 27096930 PMC4838263 · DOI
  65. Türei D, Korcsmáros T, Saez-Rodriguez J. 2016 OmniPath: guidelines and gateway for literature-curated signaling pathway resources. Nat Methods 13: 966– 967. 10.1038/nmeth.4077 27898060 · DOI
  66. The UniProt Consortium. 2017 UniProt: the universal protein knowledgebase. Nucleic Acids Res 45: D158– D169. 10.1093/nar/gkw1099 27899622 PMC5210571 · DOI · Paper page
  67. van de Peppel J, Strini T, Tilburg J, Westerhoff H, van Wijnen AJ, van Leeuwen JP. 2017 Identification of three early phases of cell-fate determination during osteogenic and adipogenic differentiation by transcription factor dynamics. Stem Cell Reports 8: 947– 960. 10.1016/j.stemcr.2017.02.018 28344004 PMC5390132 · DOI
  68. Wang L, Hurley DG, Watkins W, Araki H, Tamada Y, Muthukaruppan A, Ranjard L, Derkac E, Imoto S, Miyano S, 2012 Cell cycle gene networks are associated with melanoma prognosis. PLoS One 7: e34247 10.1371/journal.pone.0034247 22536322 PMC3335030 · DOI
  69. Wingender E, Schoeps T, Dönitz J. 2013 TFClass: an expandable hierarchical classification of human transcription factors. Nucleic Acids Res 41: D165– D170. 10.1093/nar/gks1123 23180794 PMC3531165 · DOI
  70. Yang A, Zhu Z, Kapranov P, McKeon F, Church GM, Gingeras TR, Struhl K. 2006 Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells. Mol Cell 24: 593– 602. 10.1016/j.molcel.2006.10.018 17188034 · DOI
  71. Yusuf D, Butland SL, Swanson MI, Bolotin E, Ticoll A, Cheung WA, Zhang XYC, Dickman CTD, Fulton DL, Lim JS, 2012 The Transcription Factor Encyclopedia. Genome Biol 13: R24 10.1186/gb-2012-13-3-r24 22458515 PMC3439975 · DOI
  72. Zeller KI, Jegga AG, Aronow BJ, O'Donnell KA, Dang CV. 2003 An integrated database of genes responsive to the Myc oncogenic transcription factor: identification of direct genomic targets. Genome Biol 4: R69 10.1186/gb-2003-4-10-r69 14519204 PMC328458 · DOI

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Authors
García‐Alonso, L., Holland, C. H., Ibrahim, M. M., Türei, D., & Sáez-Rodríguez, J.
Affiliations
  • European Bioinformatics Institute (GB)
  • Heidelberg University (DE)
  • RWTH Aachen University (DE)
Venue
Genome Research
Published
2019-07-24
Volume
29
Issue
8
Pages
1363-1375
ISSN
  • 1088-9051 (ISSN-L)
  • 1549-5469
OpenAlex
W2964315448
Cited by
1,122
References
9
Citations by year
2026: 221 · 2025: 192 · 2024: 240 · 2023: 180 · 2022: 146 · 2021: 88 · 2020: 43 · 2019: 11
Type
posted content
Language
en
Open access
Licence
other-oa
Locations
  • Genome Research (publishedVersion, other-oa)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
  • RWTH Publications (RWTH Aachen)
Funders
  • Open Targets (OTAR016)
  • Germany Federal Ministry of Education and Research (FKZ 031L0041)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords
transcription factor regulons, human transcription factors, confidence scores
MeSH terms
Binding Sites, Chromatin, DNA, Neoplasm, Humans, Neoplasm Proteins, Neoplasms, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Transcription, Genetic, Regulon, Computational Biology, Benchmarking, Chromatin Immunoprecipitation, Gene Regulatory Networks, Datasets as Topic

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