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Integrative Analysis of Omics Big Data

  • Protocol
Computational Systems Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1754))

Abstract

The diversity and huge omics data take biology and biomedicine research and application into a big data era, just like that popular in human society a decade ago. They are opening a new challenge from horizontal data ensemble (e.g., the similar types of data collected from different labs or companies) to vertical data ensemble (e.g., the different types of data collected for a group of person with match information), which requires the integrative analysis in biology and biomedicine and also asks for emergent development of data integration to address the great changes from previous population-guided to newly individual-guided investigations.

Data integration is an effective concept to solve the complex problem or understand the complicate system. Several benchmark studies have revealed the heterogeneity and trade-off that existed in the analysis of omics data. Integrative analysis can combine and investigate many datasets in a cost-effective reproducible way. Current integration approaches on biological data have two modes: one is “bottom-up integration” mode with follow-up manual integration, and the other one is “top-down integration” mode with follow-up in silico integration.

This paper will firstly summarize the combinatory analysis approaches to give candidate protocol on biological experiment design for effectively integrative study on genomics and then survey the data fusion approaches to give helpful instruction on computational model development for biological significance detection, which have also provided newly data resources and analysis tools to support the precision medicine dependent on the big biomedical data. Finally, the problems and future directions are highlighted for integrative analysis of omics big data.

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References

  1. Field D, Sansone SA, Collis A, Booth T, Dukes P, Gregurick SK, Kennedy K, Kolar P, Kolker E, Maxon M, Millard S, Mugabushaka AM, Perrin N, Remacle JE, Remington K, Rocca-Serra P, Taylor CF, Thorley M, Tiwari B, Wilbanks J (2009) Megascience. ‘Omics data sharing’. Science 326(5950):234–236. https://doi.org/10.1126/science.1180598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Vo TV, Das J, Meyer MJ, Cordero NA, Akturk N, Wei X, Fair BJ, Degatano AG, Fragoza R, Liu LG, Matsuyama A, Trickey M, Horibata S, Grimson A, Yamano H, Yoshida M, Roth FP, Pleiss JA, Xia Y, Yu H (2016) A proteome-wide fission yeast interactome reveals network evolution principles from yeasts to human. Cell 164(1–2):310–323. https://doi.org/10.1016/j.cell.2015.11.037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Madhani HD, Francis NJ, Kingston RE, Kornberg RD, Moazed D, Narlikar GJ, Panning B, Struhl K (2008) Epigenomics: a roadmap, but to where? Science 322(5898):43–44. https://doi.org/10.1126/science.322.5898.43b

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Romanoski CE, Glass CK, Stunnenberg HG, Wilson L, Almouzni G (2015) Epigenomics: roadmap for regulation. Nature 518(7539):314–316. https://doi.org/10.1038/518314a

    Article  CAS  PubMed  Google Scholar 

  5. Lage K, Karlberg EO, Storling ZM, Olason PI, Pedersen AG, Rigina O, Hinsby AM, Tumer Z, Pociot F, Tommerup N, Moreau Y, Brunak S (2007) A human phenome-interactome network of protein complexes implicated in genetic disorders. Nat Biotechnol 25(3):309–316. https://doi.org/10.1038/nbt1295

    Article  CAS  PubMed  Google Scholar 

  6. Nicholson JK, Lindon JC (2008) Systems biology: metabonomics. Nature 455(7216):1054–1056. https://doi.org/10.1038/4551054a

    Article  CAS  PubMed  Google Scholar 

  7. Rolland T, Tasan M, Charloteaux B, Pevzner SJ, Zhong Q, Sahni N, Yi S, Lemmens I, Fontanillo C, Mosca R, Kamburov A, Ghiassian SD, Yang X, Ghamsari L, Balcha D, Begg BE, Braun P, Brehme M, Broly MP, Carvunis AR, Convery-Zupan D, Corominas R, Coulombe-Huntington J, Dann E, Dreze M, Dricot A, Fan C, Franzosa E, Gebreab F, Gutierrez BJ, Hardy MF, Jin M, Kang S, Kiros R, Lin GN, Luck K, MacWilliams A, Menche J, Murray RR, Palagi A, Poulin MM, Rambout X, Rasla J, Reichert P, Romero V, Ruyssinck E, Sahalie JM, Scholz A, Shah AA, Sharma A, Shen Y, Spirohn K, Tam S, Tejeda AO, Trigg SA, Twizere JC, Vega K, Walsh J, Cusick ME, Xia Y, Barabasi AL, Iakoucheva LM, Aloy P, De Las Rivas J, Tavernier J, Calderwood MA, Hill DE, Hao T, Roth FP, Vidal M (2014) A proteome-scale map of the human interactome network. Cell 159(5):1212–1226. https://doi.org/10.1016/j.cell.2014.10.050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Friedel CC, Zimmer R (2006) Toward the complete interactome. Nat Biotechnol 24(6):614–615.; Author reply 615. https://doi.org/10.1038/nbt0606-614

    Article  CAS  PubMed  Google Scholar 

  9. Buxton B, Hayward V, Pearson I, Karkkainen L, Greiner H, Dyson E, Ito J, Chung A, Kelly K, Schillace S (2008) Big data: the next Google. Interview by Duncan Graham-Rowe. Nature 455(7209):8–9. https://doi.org/10.1038/455008a

    Article  CAS  PubMed  Google Scholar 

  10. Kirk P, Griffin JE, Savage RS, Ghahramani Z, Wild DL (2012) Bayesian correlated clustering to integrate multiple datasets. Bioinformatics 28(24):3290–3297. https://doi.org/10.1093/bioinformatics/bts595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mo Q, Wang S, Seshan VE, Olshen AB, Schultz N, Sander C, Powers RS, Ladanyi M, Shen R (2013) Pattern discovery and cancer gene identification in integrated cancer genomic data. Proc Natl Acad Sci U S A 110(11):4245–4250. https://doi.org/10.1073/pnas.1208949110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rapport DJ, Maffi L (2013) A call for integrative thinking. Science 339(6123):1032. https://doi.org/10.1126/science.339.6123.1032-a

    Article  CAS  PubMed  Google Scholar 

  13. Wen Y, Wei Y, Zhang S, Li S, Liu H, Wang F, Zhao Y, Zhang D, Zhang Y (2016) Cell subpopulation deconvolution reveals breast cancer heterogeneity based on DNA methylation signature. Brief Bioinform. https://doi.org/10.1093/bib/bbw028

  14. Voillet V, Besse P, Liaubet L, San Cristobal M, Gonzalez I (2016) Handling missing rows in multi-omics data integration: multiple imputation in multiple factor analysis framework. BMC Bioinformatics 17(1):402. https://doi.org/10.1186/s12859-016-1273-5

    Article  PubMed  PubMed Central  Google Scholar 

  15. Weischenfeldt J, Simon R, Feuerbach L, Schlangen K, Weichenhan D, Minner S, Wuttig D, Warnatz HJ, Stehr H, Rausch T, Jager N, Gu L, Bogatyrova O, Stutz AM, Claus R, Eils J, Eils R, Gerhauser C, Huang PH, Hutter B, Kabbe R, Lawerenz C, Radomski S, Bartholomae CC, Falth M, Gade S, Schmidt M, Amschler N, Hass T, Galal R, Gjoni J, Kuner R, Baer C, Masser S, von Kalle C, Zichner T, Benes V, Raeder B, Mader M, Amstislavskiy V, Avci M, Lehrach H, Parkhomchuk D, Sultan M, Burkhardt L, Graefen M, Huland H, Kluth M, Krohn A, Sirma H, Stumm L, Steurer S, Grupp K, Sultmann H, Sauter G, Plass C, Brors B, Yaspo ML, Korbel JO, Schlomm T (2013) Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer. Cancer Cell 23(2):159–170. https://doi.org/10.1016/j.ccr.2013.01.002

    Article  CAS  PubMed  Google Scholar 

  16. Shen R, Mo Q, Schultz N, Seshan VE, Olshen AB, Huse J, Ladanyi M, Sander C (2012) Integrative subtype discovery in glioblastoma using iCluster. PLoS One 7(4):e35236. https://doi.org/10.1371/journal.pone.0035236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zeng T, Wang DC, Wang X, Xu F, Chen L (2014) Prediction of dynamical drug sensitivity and resistance by module network rewiring-analysis based on transcriptional profiling. Drug Resist Updates 17(3):64–76. https://doi.org/10.1016/j.drup.2014.08.002

    Article  Google Scholar 

  18. Shi X, Shen S, Liu J, Huang J, Zhou Y, Ma S (2014) Similarity of markers identified from cancer gene expression studies: observations from GEO. Brief Bioinform 15(5):671–684. https://doi.org/10.1093/bib/bbt044

    Article  PubMed  Google Scholar 

  19. Shi X, Yi H, Ma S (2015) Measures for the degree of overlap of gene signatures and applications to TCGA. Brief Bioinform 16(5):735–744. https://doi.org/10.1093/bib/bbu049

    Article  CAS  PubMed  Google Scholar 

  20. Bebek G, Koyuturk M, Price ND, Chance MR (2012) Network biology methods integrating biological data for translational science. Brief Bioinform 13(4):446–459. https://doi.org/10.1093/bib/bbr075

    Article  PubMed  PubMed Central  Google Scholar 

  21. Zhang S, Liu CC, Li W, Shen H, Laird PW, Zhou XJ (2012) Discovery of multi-dimensional modules by integrative analysis of cancer genomic data. Nucleic Acids Res 40(19):9379–9391. https://doi.org/10.1093/nar/gks725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Liu Y, Devescovi V, Chen S, Nardini C (2013) Multilevel omic data integration in cancer cell lines: advanced annotation and emergent properties. BMC Syst Biol 7:14. https://doi.org/10.1186/1752-0509-7-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hieke S, Benner A, Schlenl RF, Schumacher M, Bullinger L, Binder H (2016) Integrating multiple molecular sources into a clinical risk prediction signature by extracting complementary information. BMC Bioinformatics 17(1):327. https://doi.org/10.1186/s12859-016-1183-6

    Article  PubMed  PubMed Central  Google Scholar 

  24. Shen R, Olshen AB, Ladanyi M (2009) Integrative clustering of multiple genomic data types using a joint latent variable model with application to breast and lung cancer subtype analysis. Bioinformatics 25(22):2906–2912. https://doi.org/10.1093/bioinformatics/btp543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang W, Baladandayuthapani V, Morris JS, Broom BM, Manyam G, Do KA (2013) iBAG: integrative Bayesian analysis of high-dimensional multiplatform genomics data. Bioinformatics 29(2):149–159. https://doi.org/10.1093/bioinformatics/bts655

    Article  CAS  PubMed  Google Scholar 

  26. Yuan Y, Savage RS, Markowetz F (2011) Patient-specific data fusion defines prognostic cancer subtypes. PLoS Comput Biol 7(10):e1002227. https://doi.org/10.1371/journal.pcbi.1002227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Speicher NK, Pfeifer N (2015) Integrating different data types by regularized unsupervised multiple kernel learning with application to cancer subtype discovery. Bioinformatics 31(12):i268–i275. https://doi.org/10.1093/bioinformatics/btv244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Narayanan M, Vetta A, Schadt EE, Zhu J (2010) Simultaneous clustering of multiple gene expression and physical interaction datasets. PLoS Comput Biol 6(4):e1000742. https://doi.org/10.1371/journal.pcbi.1000742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kutalik Z, Beckmann JS, Bergmann S (2008) A modular approach for integrative analysis of large-scale gene-expression and drug-response data. Nat Biotechnol 26(5):531–539. https://doi.org/10.1038/nbt1397

    Article  CAS  PubMed  Google Scholar 

  30. Le Van T, van Leeuwen M, Carolina Fierro A, De Maeyer D, Van den Eynden J, Verbeke L, De Raedt L, Marchal K, Nijssen S (2016) Simultaneous discovery of cancer subtypes and subtype features by molecular data integration. Bioinformatics 32(17):i445–i454. https://doi.org/10.1093/bioinformatics/btw434

    Article  CAS  PubMed  Google Scholar 

  31. Seely JS, Kaufman MT, Ryu SI, Shenoy KV, Cunningham JP, Churchland MM (2016) Tensor analysis reveals distinct population structure that parallels the different computational roles of areas M1 and V1. PLoS Comput Biol 12(11):e1005164. https://doi.org/10.1371/journal.pcbi.1005164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hore V, Vinuela A, Buil A, Knight J, McCarthy MI, Small K, Marchini J (2016) Tensor decomposition for multiple-tissue gene expression experiments. Nat Genet 48(9):1094–1100. https://doi.org/10.1038/ng.3624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bersanelli M, Mosca E, Remondini D, Giampieri E, Sala C, Castellani G, Milanesi L (2016) Methods for the integration of multi-omics data: mathematical aspects. BMC Bioinformatics 17(Suppl 2):15. https://doi.org/10.1186/s12859-015-0857-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Meng C, Zeleznik OA, Thallinger GG, Kuster B, Gholami AM, Culhane AC (2016) Dimension reduction techniques for the integrative analysis of multi-omics data. Brief Bioinform 17(4):628–641. https://doi.org/10.1093/bib/bbv108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Luo Y, Wang F, Szolovits P (2016) Tensor factorization toward precision medicine. Brief Bioinform. https://doi.org/10.1093/bib/bbw026

  36. Vargas AJ, Harris CC (2016) Biomarker development in the precision medicine era: lung cancer as a case study. Nat Rev Cancer 16(8):525–537. https://doi.org/10.1038/nrc.2016.56

    Article  CAS  PubMed  Google Scholar 

  37. Lahti L, Schafer M, Klein HU, Bicciato S, Dugas M (2013) Cancer gene prioritization by integrative analysis of mRNA expression and DNA copy number data: a comparative review. Brief Bioinform 14(1):27–35. https://doi.org/10.1093/bib/bbs005

    Article  CAS  PubMed  Google Scholar 

  38. Genomes Project C, Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491(7422):56–65. https://doi.org/10.1038/nature11632

    Article  CAS  Google Scholar 

  39. Gerstein M (2012) Genomics: ENCODE leads the way on big data. Nature 489(7415):208. https://doi.org/10.1038/489208b

    Article  CAS  PubMed  Google Scholar 

  40. Nagano T, Lubling Y, Stevens TJ, Schoenfelder S, Yaffe E, Dean W, Laue ED, Tanay A, Fraser P (2013) Single-cell Hi-C reveals cell-to-cell variability in chromosome structure. Nature 502(7469):59–64. https://doi.org/10.1038/nature12593

    Article  CAS  PubMed  Google Scholar 

  41. Dekker J, Marti-Renom MA, Mirny LA (2013) Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data. Nat Rev Genet 14(6):390–403. https://doi.org/10.1038/nrg3454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Yun X, Xia L, Tang B, Zhang H, Li F, Zhang Z (2016) 3CDB: a manually curated database of chromosome conformation capture data. Database (Oxford). https://doi.org/10.1093/database/baw044

    Article  Google Scholar 

  43. Teng L, He B, Wang J, Tan K (2016) 4DGenome: a comprehensive database of chromatin interactions. Bioinformatics 32(17):2727. https://doi.org/10.1093/bioinformatics/btw375

    Article  CAS  PubMed  Google Scholar 

  44. Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, Yefanov A, Lee H, Zhang N, Robertson CL, Serova N, Davis S, Soboleva A (2013) NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res 41(Database issue):D991–D995. https://doi.org/10.1093/nar/gks1193

    Article  CAS  PubMed  Google Scholar 

  45. Kim HS, Minna JD, White MA (2013) GWAS meets TCGA to illuminate mechanisms of cancer predisposition. Cell 152(3):387–389. https://doi.org/10.1016/j.cell.2013.01.027

    Article  CAS  PubMed  Google Scholar 

  46. International Cancer Genome C, Hudson TJ, Anderson W, Artez A, Barker AD, Bell C, Bernabe RR, Bhan MK, Calvo F, Eerola I, Gerhard DS, Guttmacher A, Guyer M, Hemsley FM, Jennings JL, Kerr D, Klatt P, Kolar P, Kusada J, Lane DP, Laplace F, Youyong L, Nettekoven G, Ozenberger B, Peterson J, Rao TS, Remacle J, Schafer AJ, Shibata T, Stratton MR, Vockley JG, Watanabe K, Yang H, Yuen MM, Knoppers BM, Bobrow M, Cambon-Thomsen A, Dressler LG, Dyke SO, Joly Y, Kato K, Kennedy KL, Nicolas P, Parker MJ, Rial-Sebbag E, Romeo-Casabona CM, Shaw KM, Wallace S, Wiesner GL, Zeps N, Lichter P, Biankin AV, Chabannon C, Chin L, Clement B, de Alava E, Degos F, Ferguson ML, Geary P, Hayes DN, Hudson TJ, Johns AL, Kasprzyk A, Nakagawa H, Penny R, Piris MA, Sarin R, Scarpa A, Shibata T, van de Vijver M, Futreal PA, Aburatani H, Bayes M, Botwell DD, Campbell PJ, Estivill X, Gerhard DS, Grimmond SM, Gut I, Hirst M, Lopez-Otin C, Majumder P, Marra M, McPherson JD, Nakagawa H, Ning Z, Puente XS, Ruan Y, Shibata T, Stratton MR, Stunnenberg HG, Swerdlow H, Velculescu VE, Wilson RK, Xue HH, Yang L, Spellman PT, Bader GD, Boutros PC, Campbell PJ, Flicek P, Getz G, Guigo R, Guo G, Haussler D, Heath S, Hubbard TJ, Jiang T, Jones SM, Li Q, Lopez-Bigas N, Luo R, Muthuswamy L, Ouellette BF, Pearson JV, Puente XS, Quesada V, Raphael BJ, Sander C, Shibata T, Speed TP, Stein LD, Stuart JM, Teague JW, Totoki Y, Tsunoda T, Valencia A, Wheeler DA, Wu H, Zhao S, Zhou G, Stein LD, Guigo R, Hubbard TJ, Joly Y, Jones SM, Kasprzyk A, Lathrop M, Lopez-Bigas N, Ouellette BF, Spellman PT, Teague JW, Thomas G, Valencia A, Yoshida T, Kennedy KL, Axton M, Dyke SO, Futreal PA, Gerhard DS, Gunter C, Guyer M, Hudson TJ, McPherson JD, Miller LJ, Ozenberger B, Shaw KM, Kasprzyk A, Stein LD, Zhang J, Haider SA, Wang J, Yung CK, Cros A, Liang Y, Gnaneshan S, Guberman J, Hsu J, Bobrow M, Chalmers DR, Hasel KW, Joly Y, Kaan TS, Kennedy KL, Knoppers BM, Lowrance WW, Masui T, Nicolas P, Rial-Sebbag E, Rodriguez LL, Vergely C, Yoshida T, Grimmond SM, Biankin AV, Bowtell DD, Cloonan N, deFazio A, Eshleman JR, Etemadmoghadam D, Gardiner BB, Kench JG, Scarpa A, Sutherland RL, Tempero MA, Waddell NJ, Wilson PJ, McPherson JD, Gallinger S, Tsao MS, Shaw PA, Petersen GM, Mukhopadhyay D, Chin L, DePinho RA, Thayer S, Muthuswamy L, Shazand K, Beck T, Sam M, Timms L, Ballin V, Lu Y, Ji J, Zhang X, Chen F, Hu X, Zhou G, Yang Q, Tian G, Zhang L, Xing X, Li X, Zhu Z, Yu Y, Yu J, Yang H, Lathrop M, Tost J, Brennan P, Holcatova I, Zaridze D, Brazma A, Egevard L, Prokhortchouk E, Banks RE, Uhlen M, Cambon-Thomsen A, Viksna J, Ponten F, Skryabin K, Stratton MR, Futreal PA, Birney E, Borg A, Borresen-Dale AL, Caldas C, Foekens JA, Martin S, Reis-Filho JS, Richardson AL, Sotiriou C, Stunnenberg HG, Thoms G, van de Vijver M, van't Veer L, Calvo F, Birnbaum D, Blanche H, Boucher P, Boyault S, Chabannon C, Gut I, Masson-Jacquemier JD, Lathrop M, Pauporte I, Pivot X, Vincent-Salomon A, Tabone E, Theillet C, Thomas G, Tost J, Treilleux I, Calvo F, Bioulac-Sage P, Clement B, Decaens T, Degos F, Franco D, Gut I, Gut M, Heath S, Lathrop M, Samuel D, Thomas G, Zucman-Rossi J, Lichter P, Eils R, Brors B, Korbel JO, Korshunov A, Landgraf P, Lehrach H, Pfister S, Radlwimmer B, Reifenberger G, Taylor MD, von Kalle C, Majumder PP, Sarin R, Rao TS, Bhan MK, Scarpa A, Pederzoli P, Lawlor RA, Delledonne M, Bardelli A, Biankin AV, Grimmond SM, Gress T, Klimstra D, Zamboni G, Shibata T, Nakamura Y, Nakagawa H, Kusada J, Tsunoda T, Miyano S, Aburatani H, Kato K, Fujimoto A, Yoshida T, Campo E, Lopez-Otin C, Estivill X, Guigo R, de Sanjose S, Piris MA, Montserrat E, Gonzalez-Diaz M, Puente XS, Jares P, Valencia A, Himmelbauer H, Quesada V, Bea S, Stratton MR, Futreal PA, Campbell PJ, Vincent-Salomon A, Richardson AL, Reis-Filho JS, van de Vijver M, Thomas G, Masson-Jacquemier JD, Aparicio S, Borg A, Borresen-Dale AL, Caldas C, Foekens JA, Stunnenberg HG, van't Veer L, Easton DF, Spellman PT, Martin S, Barker AD, Chin L, Collins FS, Compton CC, Ferguson ML, Gerhard DS, Getz G, Gunter C, Guttmacher A, Guyer M, Hayes DN, Lander ES, Ozenberger B, Penny R, Peterson J, Sander C, Shaw KM, Speed TP, Spellman PT, Vockley JG, Wheeler DA, Wilson RK, Hudson TJ, Chin L, Knoppers BM, Lander ES, Lichter P, Stein LD, Stratton MR, Anderson W, Barker AD, Bell C, Bobrow M, Burke W, Collins FS, Compton CC, DePinho RA, Easton DF, Futreal PA, Gerhard DS, Green AR, Guyer M, Hamilton SR, Hubbard TJ, Kallioniemi OP, Kennedy KL, Ley TJ, Liu ET, Lu Y, Majumder P, Marra M, Ozenberger B, Peterson J, Schafer AJ, Spellman PT, Stunnenberg HG, Wainwright BJ, Wilson RK, Yang H (2010) International network of cancer genome projects. Nature 464(7291):993–998. https://doi.org/10.1038/nature08987

    Article  CAS  Google Scholar 

  47. Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42(Database issue):D68–D73. https://doi.org/10.1093/nar/gkt1181

    Article  CAS  Google Scholar 

  48. Quek XC, Thomson DW, Maag JL, Bartonicek N, Signal B, Clark MB, Gloss BS, Dinger ME (2015) lncRNAdb v2.0: expanding the reference database for functional long noncoding RNAs. Nucleic Acids Res 43(Database issue):D168–D173. https://doi.org/10.1093/nar/gku988

    Article  CAS  PubMed  Google Scholar 

  49. Lebron R, Gomez-Martin C, Carpena P, Bernaola-Galvan P, Barturen G, Hackenberg M, Oliver JL (2017) NGSmethDB 2017: enhanced methylomes and differential methylation. Nucleic Acids Res 45(D1):D97–D103. https://doi.org/10.1093/nar/gkw996

    Article  CAS  PubMed  Google Scholar 

  50. Xin Y, Chanrion B, O'Donnell AH, Milekic M, Costa R, Ge Y, Haghighi FG (2012) MethylomeDB: a database of DNA methylation profiles of the brain. Nucleic Acids Res 40(Database issue):D1245–D1249. https://doi.org/10.1093/nar/gkr1193

    Article  CAS  PubMed  Google Scholar 

  51. Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Aziat F, Dong E, Bouatra S, Sinelnikov I, Arndt D, Xia J, Liu P, Yallou F, Bjorndahl T, Perez-Pineiro R, Eisner R, Allen F, Neveu V, Greiner R, Scalbert A (2013) HMDB 3.0—the human metabolome database in 2013. Nucleic Acids Res 41(Database issue):D801–D807. https://doi.org/10.1093/nar/gks1065

    Article  CAS  Google Scholar 

  52. Mitchell A, Bucchini F, Cochrane G, Denise H, ten Hoopen P, Fraser M, Pesseat S, Potter S, Scheremetjew M, Sterk P, Finn RD (2016) EBI metagenomics in 2016—an expanding and evolving resource for the analysis and archiving of metagenomic data. Nucleic Acids Res 44(D1):D595–D603. https://doi.org/10.1093/nar/gkv1195

    Article  CAS  PubMed  Google Scholar 

  53. Friedman A, Perrimon N (2007) Genetic screening for signal transduction in the era of network biology. Cell 128(2):225–231. https://doi.org/10.1016/j.cell.2007.01.007

    Article  CAS  PubMed  Google Scholar 

  54. Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell's functional organization. Nat Rev Genet 5(2):101–113. https://doi.org/10.1038/nrg1272

    Article  CAS  PubMed  Google Scholar 

  55. Goymer P (2008) Network biology: why do we need hubs? Nat Rev Genet 9(9):650

    Article  CAS  Google Scholar 

  56. Hu JX, Thomas CE, Brunak S (2016) Network biology concepts in complex disease comorbidities. Nat Rev Genet 17(10):615–629. https://doi.org/10.1038/nrg.2016.87

    Article  CAS  PubMed  Google Scholar 

  57. New AM, Lehner B (2015) Systems biology: network evolution hinges on history. Nature 523(7560):297–298. https://doi.org/10.1038/nature14537

    Article  CAS  PubMed  Google Scholar 

  58. Chatr-Aryamontri A, Oughtred R, Boucher L, Rust J, Chang C, Kolas NK, O'Donnell L, Oster S, Theesfeld C, Sellam A, Stark C, Breitkreutz BJ, Dolinski K, Tyers M (2017) The BioGRID interaction database: 2017 update. Nucleic Acids Res 45(D1):D369–D379. https://doi.org/10.1093/nar/gkw1102

    Article  CAS  PubMed  Google Scholar 

  59. Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C (2015) STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43(Database issue):D447–D452. https://doi.org/10.1093/nar/gku1003

    Article  CAS  PubMed  Google Scholar 

  60. Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K (2017) KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 45(D1):D353–D361. https://doi.org/10.1093/nar/gkw1092

    Article  CAS  PubMed  Google Scholar 

  61. Fabregat A, Sidiropoulos K, Garapati P, Gillespie M, Hausmann K, Haw R, Jassal B, Jupe S, Korninger F, McKay S, Matthews L, May B, Milacic M, Rothfels K, Shamovsky V, Webber M, Weiser J, Williams M, Wu G, Stein L, Hermjakob H, D'Eustachio P (2016) The reactome pathway knowledgebase. Nucleic Acids Res 44(D1):D481–D487. https://doi.org/10.1093/nar/gkv1351

    Article  CAS  PubMed  Google Scholar 

  62. Bohler A, Wu G, Kutmon M, Pradhana LA, Coort SL, Hanspers K, Haw R, Pico AR, Evelo CT (2016) Reactome from a WikiPathways perspective. PLoS Comput Biol 12(5):e1004941. https://doi.org/10.1371/journal.pcbi.1004941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Tyner C, Barber GP, Casper J, Clawson H, Diekhans M, Eisenhart C, Fischer CM, Gibson D, Gonzalez JN, Guruvadoo L, Haeussler M, Heitner S, Hinrichs AS, Karolchik D, Lee BT, Lee CM, Nejad P, Raney BJ, Rosenbloom KR, Speir ML, Villarreal C, Vivian J, Zweig AS, Haussler D, Kuhn RM, Kent WJ (2017) The UCSC Genome Browser database: 2017 update. Nucleic Acids Res 45(D1):D626–D634. https://doi.org/10.1093/nar/gkw1134

    Article  CAS  PubMed  Google Scholar 

  64. Koch A, De Meyer T, Jeschke J, Van Criekinge W (2015) MEXPRESS: visualizing expression, DNA methylation and clinical TCGA data. BMC Genomics 16:636. https://doi.org/10.1186/s12864-015-1847-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415(6871):530–536. https://doi.org/10.1038/415530a

    Article  PubMed  Google Scholar 

  66. Zeng T, Li J (2010) Maximization of negative correlations in time-course gene expression data for enhancing understanding of molecular pathways. Nucleic Acids Res 38(1):e1. https://doi.org/10.1093/nar/gkp822

    Article  CAS  PubMed  Google Scholar 

  67. Zeng T, Guo X, Liu J (2014) Negative correlation based gene markers identification in integrative gene expression data. Int J Data Min Bioinform 10(1):1–17

    Article  Google Scholar 

  68. Deng M, Bragelmann J, Schultze JL, Perner S (2016) Web-TCGA: an online platform for integrated analysis of molecular cancer data sets. BMC Bioinformatics 17:72. https://doi.org/10.1186/s12859-016-0917-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Huang Y, Zaas AK, Rao A, Dobigeon N, Woolf PJ, Veldman T, Oien NC, McClain MT, Varkey JB, Nicholson B, Carin L, Kingsmore S, Woods CW, Ginsburg GS, Hero AO III (2011) Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection. PLoS Genet 7(8):e1002234. https://doi.org/10.1371/journal.pgen.1002234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Brawand D, Soumillon M, Necsulea A, Julien P, Csardi G, Harrigan P, Weier M, Liechti A, Aximu-Petri A, Kircher M, Albert FW, Zeller U, Khaitovich P, Grutzner F, Bergmann S, Nielsen R, Paabo S, Kaessmann H (2011) The evolution of gene expression levels in mammalian organs. Nature 478(7369):343–348. https://doi.org/10.1038/nature10532

    Article  CAS  PubMed  Google Scholar 

  71. Leek JT, Storey JD (2007) Capturing heterogeneity in gene expression studies by surrogate variable analysis. PLoS Genet 3(9):1724–1735. https://doi.org/10.1371/journal.pgen.0030161

    Article  CAS  PubMed  Google Scholar 

  72. Manimaran S, Selby HM, Okrah K, Ruberman C, Leek JT, Quackenbush J, Haibe-Kains B, Bravo HC, Johnson WE (2016) BatchQC: interactive software for evaluating sample and batch effects in genomic data. Bioinformatics. https://doi.org/10.1093/bioinformatics/btw538

    Article  CAS  Google Scholar 

  73. Vandenbon A, Dinh VH, Mikami N, Kitagawa Y, Teraguchi S, Ohkura N, Sakaguchi S (2016) Immuno-Navigator, a batch-corrected coexpression database, reveals cell type-specific gene networks in the immune system. Proc Natl Acad Sci U S A 113(17):E2393–E2402. https://doi.org/10.1073/pnas.1604351113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Johnson WE, Li C, Rabinovic A (2007) Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8(1):118–127. https://doi.org/10.1093/biostatistics/kxj037

    Article  PubMed  Google Scholar 

  75. Stein CK, Qu P, Epstein J, Buros A, Rosenthal A, Crowley J, Morgan G, Barlogie B (2015) Removing batch effects from purified plasma cell gene expression microarrays with modified ComBat. BMC Bioinformatics 16:63. https://doi.org/10.1186/s12859-015-0478-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Reese SE, Archer KJ, Therneau TM, Atkinson EJ, Vachon CM, de Andrade M, Kocher JP, Eckel-Passow JE (2013) A new statistic for identifying batch effects in high-throughput genomic data that uses guided principal component analysis. Bioinformatics 29(22):2877–2883. https://doi.org/10.1093/bioinformatics/btt480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Song R, Huang J, Ma S (2012) Integrative prescreening in analysis of multiple cancer genomic studies. BMC Bioinformatics 13:168. https://doi.org/10.1186/1471-2105-13-168

    Article  PubMed  PubMed Central  Google Scholar 

  78. Huang X, Stern DF, Zhao H (2016) Transcriptional profiles from paired normal samples offer complementary information on cancer patient survival—evidence from TCGA pan-cancer data. Sci Rep 6:20567. https://doi.org/10.1038/srep20567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Hwang TH, Atluri G, Kuang R, Kumar V, Starr T, Silverstein KA, Haverty PM, Zhang Z, Liu J (2013) Large-scale integrative network-based analysis identifies common pathways disrupted by copy number alterations across cancers. BMC Genomics 14:440. https://doi.org/10.1186/1471-2164-14-440

    Article  PubMed  PubMed Central  Google Scholar 

  80. Li Q, Seo JH, Stranger B, McKenna A, Pe'er I, Laframboise T, Brown M, Tyekucheva S, Freedman ML (2013) Integrative eQTL-based analyses reveal the biology of breast cancer risk loci. Cell 152(3):633–641. https://doi.org/10.1016/j.cell.2012.12.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Peifer M, Fernandez-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, Plenker D, Leenders F, Sun R, Zander T, Menon R, Koker M, Dahmen I, Muller C, Di Cerbo V, Schildhaus HU, Altmuller J, Baessmann I, Becker C, de Wilde B, Vandesompele J, Bohm D, Ansen S, Gabler F, Wilkening I, Heynck S, Heuckmann JM, Lu X, Carter SL, Cibulskis K, Banerji S, Getz G, Park KS, Rauh D, Grutter C, Fischer M, Pasqualucci L, Wright G, Wainer Z, Russell P, Petersen I, Chen Y, Stoelben E, Ludwig C, Schnabel P, Hoffmann H, Muley T, Brockmann M, Engel-Riedel W, Muscarella LA, Fazio VM, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman DA, Snijders PJ, Cappuzzo F, Ligorio C, Damiani S, Field J, Solberg S, Brustugun OT, Lund-Iversen M, Sanger J, Clement JH, Soltermann A, Moch H, Weder W, Solomon B, Soria JC, Validire P, Besse B, Brambilla E, Brambilla C, Lantuejoul S, Lorimier P, Schneider PM, Hallek M, Pao W, Meyerson M, Sage J, Shendure J, Schneider R, Buttner R, Wolf J, Nurnberg P, Perner S, Heukamp LC, Brindle PK, Haas S, Thomas RK (2012) Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet 44(10):1104–1110. https://doi.org/10.1038/ng.2396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Cancer Genome Atlas N (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487(7407):330–337. https://doi.org/10.1038/nature11252

    Article  CAS  Google Scholar 

  83. Cancer Genome Atlas Research N (2013) Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499(7456):43–49. https://doi.org/10.1038/nature12222

    Article  CAS  Google Scholar 

  84. Cancer Genome Atlas Research N (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513(7517):202–209. https://doi.org/10.1038/nature13480

    Article  CAS  Google Scholar 

  85. Cancer Genome Atlas Research N (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507(7492):315–322. https://doi.org/10.1038/nature12965

    Article  CAS  Google Scholar 

  86. Cancer Genome Atlas N (2015) Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517(7536):576–582. https://doi.org/10.1038/nature14129

    Article  CAS  Google Scholar 

  87. Cancer Genome Atlas Research N (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455(7216):1061–1068. https://doi.org/10.1038/nature07385

    Article  CAS  Google Scholar 

  88. Cancer Genome Atlas Research N (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489(7417):519–525. https://doi.org/10.1038/nature11404

    Article  CAS  Google Scholar 

  89. Akbani R, Ng PK, Werner HM, Shahmoradgoli M, Zhang F, Ju Z, Liu W, Yang JY, Yoshihara K, Li J, Ling S, Seviour EG, Ram PT, Minna JD, Diao L, Tong P, Heymach JV, Hill SM, Dondelinger F, Stadler N, Byers LA, Meric-Bernstam F, Weinstein JN, Broom BM, Verhaak RG, Liang H, Mukherjee S, Lu Y, Mills GB (2014) A pan-cancer proteomic perspective on The Cancer Genome Atlas. Nat Commun 5:3887. https://doi.org/10.1038/ncomms4887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A, Zhang H, McLellan M, Yau C, Kandoth C, Bowlby R, Shen H, Hayat S, Fieldhouse R, Lester SC, Tse GM, Factor RE, Collins LC, Allison KH, Chen YY, Jensen K, Johnson NB, Oesterreich S, Mills GB, Cherniack AD, Robertson G, Benz C, Sander C, Laird PW, Hoadley KA, King TA, Network TR, Perou CM (2015) Comprehensive molecular portraits of invasive lobular breast cancer. Cell 163(2):506–519. https://doi.org/10.1016/j.cell.2015.09.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Cancer Genome Atlas N (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61–70. https://doi.org/10.1038/nature11412

    Article  CAS  Google Scholar 

  92. Drake JM, Paull EO, Graham NA, Lee JK, Smith BA, Titz B, Stoyanova T, Faltermeier CM, Uzunangelov V, Carlin DE, Fleming DT, Wong CK, Newton Y, Sudha S, Vashisht AA, Huang J, Wohlschlegel JA, Graeber TG, Witte ON, Stuart JM (2016) Phosphoproteome integration reveals patient-specific networks in prostate cancer. Cell 166(4):1041–1054. https://doi.org/10.1016/j.cell.2016.07.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Cancer Genome Atlas Research N, Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM (2013) The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45(10):1113–1120. https://doi.org/10.1038/ng.2764

    Article  CAS  PubMed  Google Scholar 

  94. Neapolitan R, Horvath CM, Jiang X (2015) Pan-cancer analysis of TCGA data reveals notable signaling pathways. BMC Cancer 15:516. https://doi.org/10.1186/s12885-015-1484-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Ruau D, Dudley JT, Chen R, Phillips NG, Swan GE, Lazzeroni LC, Clark JD, Butte AJ, Angst MS (2012) Integrative approach to pain genetics identifies pain sensitivity loci across diseases. PLoS Comput Biol 8(6):e1002538. https://doi.org/10.1371/journal.pcbi.1002538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Liu P, Sanalkumar R, Bresnick EH, Keles S, Dewey CN (2016) Integrative analysis with ChIP-seq advances the limits of transcript quantification from RNA-seq. Genome Res 26(8):1124–1133. https://doi.org/10.1101/gr.199174.115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Knouf EC, Garg K, Arroyo JD, Correa Y, Sarkar D, Parkin RK, Wurz K, O'Briant KC, Godwin AK, Urban ND, Ruzzo WL, Gentleman R, Drescher CW, Swisher EM, Tewari M (2012) An integrative genomic approach identifies p73 and p63 as activators of miR-200 microRNA family transcription. Nucleic Acids Res 40(2):499–510. https://doi.org/10.1093/nar/gkr731

    Article  CAS  PubMed  Google Scholar 

  98. Yan Z, Shah PK, Amin SB, Samur MK, Huang N, Wang X, Misra V, Ji H, Gabuzda D, Li C (2012) Integrative analysis of gene and miRNA expression profiles with transcription factor-miRNA feed-forward loops identifies regulators in human cancers. Nucleic Acids Res 40(17):e135. https://doi.org/10.1093/nar/gks395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Berghoff BA, Konzer A, Mank NN, Looso M, Rische T, Forstner KU, Kruger M, Klug G (2013) Integrative “omics”–approach discovers dynamic and regulatory features of bacterial stress responses. PLoS Genet 9(6):e1003576. https://doi.org/10.1371/journal.pgen.1003576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Kim M, Rai N, Zorraquino V, Tagkopoulos I (2016) Multi-omics integration accurately predicts cellular state in unexplored conditions for Escherichia coli. Nat Commun 7:13090. https://doi.org/10.1038/ncomms13090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Meng C, Helm D, Frejno M, Kuster B (2016) moCluster: identifying joint patterns across multiple omics data sets. J Proteome Res 15(3):755–765. https://doi.org/10.1021/acs.jproteome.5b00824

    Article  CAS  PubMed  Google Scholar 

  102. Wang B, Mezlini AM, Demir F, Fiume M, Tu Z, Brudno M, Haibe-Kains B, Goldenberg A (2014) Similarity network fusion for aggregating data types on a genomic scale. Nat Methods 11(3):333–337. https://doi.org/10.1038/nmeth.2810

    Article  CAS  PubMed  Google Scholar 

  103. Shi Q, Zhang C, Peng M, Yu X, Zeng T, Liu J, Chen L (2017) Pattern fusion analysis by adaptive alignment of multiple heterogeneous omics data. Bioinformatics. https://doi.org/10.1093/bioinformatics/btx176

  104. Lee CH, Alpert BO, Sankaranarayanan P, Alter O (2012) GSVD comparison of patient-matched normal and tumor aCGH profiles reveals global copy-number alterations predicting glioblastoma multiforme survival. PLoS One 7(1):e30098. https://doi.org/10.1371/journal.pone.0030098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Xiao X, Moreno-Moral A, Rotival M, Bottolo L, Petretto E (2014) Multi-tissue analysis of co-expression networks by higher-order generalized singular value decomposition identifies functionally coherent transcriptional modules. PLoS Genet 10(1):e1004006. https://doi.org/10.1371/journal.pgen.1004006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Kersey PJ, Staines DM, Lawson D, Kulesha E, Derwent P, Humphrey JC, Hughes DS, Keenan S, Kerhornou A, Koscielny G, Langridge N, McDowall MD, Megy K, Maheswari U, Nuhn M, Paulini M, Pedro H, Toneva I, Wilson D, Yates A, Birney E (2012) Ensembl genomes: an integrative resource for genome-scale data from non-vertebrate species. Nucleic Acids Res 40(Database issue):D91–D97. https://doi.org/10.1093/nar/gkr895

    Article  CAS  PubMed  Google Scholar 

  107. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C, Schultz N (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6(269):pl1. https://doi.org/10.1126/scisignal.2004088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. He S, He H, Xu W, Huang X, Jiang S, Li F, He F, Bo X (2016) ICM: a web server for integrated clustering of multi-dimensional biomedical data. Nucleic Acids Res 44(W1):W154–W159. https://doi.org/10.1093/nar/gkw378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Xia J, Fjell CD, Mayer ML, Pena OM, Wishart DS, Hancock RE (2013) INMEX—a web-based tool for integrative meta-analysis of expression data. Nucleic Acids Res 41(Web Server issue):W63–W70. https://doi.org/10.1093/nar/gkt338

    Article  PubMed  PubMed Central  Google Scholar 

  110. Tuncbag N, McCallum S, Huang SS, Fraenkel E (2012) SteinerNet: a web server for integrating ‘omic’ data to discover hidden components of response pathways. Nucleic Acids Res 40(Web Server issue):W505–W509. https://doi.org/10.1093/nar/gks445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Ovaska K, Laakso M, Haapa-Paananen S, Louhimo R, Chen P, Aittomaki V, Valo E, Nunez-Fontarnau J, Rantanen V, Karinen S, Nousiainen K, Lahesmaa-Korpinen AM, Miettinen M, Saarinen L, Kohonen P, Wu J, Westermarck J, Hautaniemi S (2010) Large-scale data integration framework provides a comprehensive view on glioblastoma multiforme. Genome Med 2(9):65. https://doi.org/10.1186/gm186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Krasnov GS, Dmitriev AA, Melnikova NV, Zaretsky AR, Nasedkina TV, Zasedatelev AS, Senchenko VN, Kudryavtseva AV (2016) CrossHub: a tool for multi-way analysis of The Cancer Genome Atlas (TCGA) in the context of gene expression regulation mechanisms. Nucleic Acids Res 44(7):e62. https://doi.org/10.1093/nar/gkv1478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Yu X, Li G, Chen L (2014) Prediction and early diagnosis of complex diseases by edge-network. Bioinformatics 30(6):852–859. https://doi.org/10.1093/bioinformatics/btt620

    Article  CAS  PubMed  Google Scholar 

  114. Zhang Q, Burdette JE, Wang JP (2014) Integrative network analysis of TCGA data for ovarian cancer. BMC Syst Biol 8:1338. https://doi.org/10.1186/s12918-014-0136-9

    Article  PubMed  PubMed Central  Google Scholar 

  115. Zhu R, Zhao Q, Zhao H, Ma S (2016) Integrating multidimensional omics data for cancer outcome. Biostatistics 17(4):605–618. https://doi.org/10.1093/biostatistics/kxw010

    Article  PubMed  PubMed Central  Google Scholar 

  116. Wang XV, Verhaak RG, Purdom E, Spellman PT, Speed TP (2011) Unifying gene expression measures from multiple platforms using factor analysis. PLoS One 6(3):e17691. https://doi.org/10.1371/journal.pone.0017691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Yu, XT., Zeng, T. (2018). Integrative Analysis of Omics Big Data. In: Huang, T. (eds) Computational Systems Biology. Methods in Molecular Biology, vol 1754. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7717-8_7

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