1932

Abstract

Pathway and cell type signatures are patterns present in transcriptome data that are associated with biological processes or phenotypic consequences. These signatures result from specific cell type and pathway expression but can require large transcriptomic compendia to detect. Machine learning techniques can be powerful tools for signature discovery through their ability to provide accurate and interpretable results. In this review, we discuss various machine learning applications to extract pathway and cell type signatures from transcriptomic compendia. We focus on the biological motivations and interpretation for both supervised and unsupervised learning approaches in this setting. We consider recent advances, including deep learning, and their applications to expanding bulk and single-cell RNA data. As data and computational resources increase, there will be more opportunities for machine learning to aid in revealing biological signatures.

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2019-07-20
2024-04-20
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Literature Cited

  1. 1. 
    Altman RB, Levitt M. 2018. What is biomedical data science and do we need an Annual Review of it?. Annu. Rev. Biomed. Data Sci. 1:i–iii
    [Google Scholar]
  2. 2. 
    Lowe R, Shirley N, Bleackley M, Dolan S, Shafee T 2017. Transcriptomics technologies. PLOS Comput. Biol. 13:5e1005457
    [Google Scholar]
  3. 3. 
    Huang S, Ernberg I, Kauffman S 2009. Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective. Semin. Cell Dev. Biol. 20:7869–76
    [Google Scholar]
  4. 4. 
    Conesa A, Madrigal P, Tarazona S, Gomez-Cabrero D, Cervera A et al. 2016. A survey of best practices for RNA-seq data analysis. Genome Biol 17:13
    [Google Scholar]
  5. 5. 
    Alpaydin E. 2016. Introduction to Machine Learning: Selected Papers of Lionel W. McKenzie Cumberland, RI: MIT Press
  6. 6. 
    Ben-Dor A, Bruhn L, Friedman N, Nachman I, Schummer M, Yakhini Z 2000. Tissue classification with gene expression profiles. J. Comput. Biol. 7:3–4559–83
    [Google Scholar]
  7. 7. 
    Golub TR. 1999. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286:5439531–37
    [Google Scholar]
  8. 8. 
    Shipp MA, Ross KN, Tamayo P, Weng AP, Kutok JL et al. 2002. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat. Med. 8:168–74
    [Google Scholar]
  9. 9. 
    Brown MPS, Grundy WN, Lin D, Cristianini N, Sugnet CW et al. 2000. Knowledge-based analysis of microarray gene expression data by using support vector machines. PNAS 97:1262–67
    [Google Scholar]
  10. 10. 
    Li J, Wong L. 2002. Identifying good diagnostic gene groups from gene expression profiles using the concept of emerging patterns. Bioinformatics 18:5725–34
    [Google Scholar]
  11. 11. 
    Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS et al. 2000. Molecular portraits of human breast tumours. Nature 406:6797747–52
    [Google Scholar]
  12. 12. 
    Liebermeister W. 2002. Linear modes of gene expression determined by independent component analysis. Bioinformatics 18:151–60
    [Google Scholar]
  13. 13. 
    Byron SA, Van Keuren-Jensen KR, Engelthaler DM, Carpten JD, Craig DW 2016. Translating RNA sequencing into clinical diagnostics: opportunities and challenges. Nat. Rev. Genet. 17:5257–71
    [Google Scholar]
  14. 14. 
    Casamassimi A, Federico A, Rienzo M, Esposito S, Ciccodicola A 2017. Transcriptome profiling in human diseases: new advances and perspectives. Int. J. Mol. Sci. 18:8e1652
    [Google Scholar]
  15. 15. 
    Chibon F. 2013. Cancer gene expression signatures—the rise and fall. Eur. J. Cancer 49:82000–9
    [Google Scholar]
  16. 16. 
    Wang Z, Gerstein M, Snyder M 2009. RNA-Seq: a revolutionary tool for transcriptomics. Nat. Rev. Genet. 10:157–63
    [Google Scholar]
  17. 17. 
    Leung MKK, Delong A, Alipanahi B, Frey BJ 2016. Machine learning in genomic medicine: a review of computational problems and data sets. Proc. IEEE 104:1176–97
    [Google Scholar]
  18. 18. 
    Kotsiantis S. 2007. Supervised machine learning: a review of classification techniques. Proceedings of the 2007 Conference on Emerging Artificial Intelligence Applications in Computer Engineering3–24 Amsterdam: IOS
    [Google Scholar]
  19. 19. 
    Tibshirani R. 1994. Regression shrinkage and selection via the lasso. J. R. Stat. Soc. Ser. B 58:1267–88
    [Google Scholar]
  20. 20. 
    Zou H, Hastie T. 2005. Regularization and variable selection via the elastic net. J. R. Stat. Soc. Ser. B 67:2301–20
    [Google Scholar]
  21. 21. 
    Breiman L. 2001. Random forests. Mach. Learn. 45:5–32
    [Google Scholar]
  22. 22. 
    Hearst MA, Dumais ST, Osuna E, Platt J, Scholkopf B 1998. Support vector machines. IEEE Intell. Syst. Appl. 13:418–28
    [Google Scholar]
  23. 23. 
    Pirooznia M, Yang JY, Yang MQ, Deng Y 2008. A comparative study of different machine learning methods on microarray gene expression data. BMC Genom 9:Suppl. 113
    [Google Scholar]
  24. 24. 
    van ’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AAM et al. 2002. Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:6871530–36
    [Google Scholar]
  25. 25. 
    Venet D, Dumont JE, Detours V 2011. Most random gene expression signatures are significantly associated with breast cancer outcome. PLOS Comput. Biol. 7:10e1002240
    [Google Scholar]
  26. 26. 
    Newman AM, Liu CL, Green MR, Gentles AJ, Feng W et al. 2015. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12:5453–57
    [Google Scholar]
  27. 27. 
    Abbas AR, Wolslegel K, Seshasayee D, Modrusan Z, Clark HF 2009. Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus. PLOS ONE 4:7e6098
    [Google Scholar]
  28. 28. 
    Li B, Severson E, Pignon J-C, Zhao H, Li T et al. 2016. Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol 17:1174
    [Google Scholar]
  29. 29. 
    Shen-Orr SS, Tibshirani R, Khatri P, Bodian DL, Staedtler F et al. 2010. Cell type–specific gene expression differences in complex tissues. Nat. Methods 7:4287–89
    [Google Scholar]
  30. 30. 
    Wang M, Master SR, Chodosh LA 2006. Computational expression deconvolution in a complex mammalian organ. BMC Bioinform 7:328
    [Google Scholar]
  31. 31. 
    Wang Y, Xia X-Q, Jia Z, Sawyers A, Yao H et al. 2010. In silico estimates of tissue components in surgical samples based on expression profiling data. Cancer Res 70:166448–55
    [Google Scholar]
  32. 32. 
    Ju W, Greene CS, Eichinger F, Nair V, Hodgin JB et al. 2013. Defining cell-type specificity at the transcriptional level in human disease. Genome Res 23:111862–73
    [Google Scholar]
  33. 33. 
    Shen-Orr SS, Gaujoux R. 2013. Computational deconvolution: extracting cell type-specific information from heterogeneous samples. Curr. Opin. Immunol. 25:5571–78
    [Google Scholar]
  34. 34. 
    Guinney J, Ferté C, Dry J, McEwen R, Manceau G et al. 2014. Modeling RAS phenotype in colorectal cancer uncovers novel molecular traits of RAS dependency and improves prediction of response to targeted agents in patients. Clin. Cancer Res. 20:1265–72
    [Google Scholar]
  35. 35. 
    Way GP, Allaway RJ, Bouley SJ, Fadul CE, Sanchez Y, Greene CS 2017. A machine learning classifier trained on cancer transcriptomes detects NF1 inactivation signal in glioblastoma. BMC Genom 18:1127
    [Google Scholar]
  36. 36. 
    Yang P, Hwa Yang Y, Zhou BB, Zomaya AY 2010. A review of ensemble methods in bioinformatics. Curr. Bioinform. 5:4296–308
    [Google Scholar]
  37. 37. 
    Way GP, Sanchez-Vega F, La K, Armenia J, Chatila WK et al. 2018. Machine learning detects pan-cancer Ras pathway activation in The Cancer Genome Atlas. Cell Rep 23:1172–80.e3
    [Google Scholar]
  38. 38. 
    Knijnenburg TA, Wang L, Zimmermann MT, Chambwe N, Gao GF et al. 2018. Genomic and molecular landscape of DNA damage repair deficiency across The Cancer Genome Atlas. Cell Rep 23:1239–54.e6
    [Google Scholar]
  39. 39. 
    Wilks C, Gaddipati P, Nellore A, Langmead B 2017. Snaptron: querying and visualizing splicing across tens of thousands of RNA-seq samples. bioRxiv 97881. https://doi.org/10.1101/097881
    [Crossref]
  40. 40. 
    Turki T, Wei Z. 2018. Boosting support vector machines for cancer discrimination tasks. Comput. Biol. Med. 101:236–49
    [Google Scholar]
  41. 41. 
    Sokolov A, Carlin DE, Paull EO, Baertsch R, Stuart JM 2016. Pathway-based genomics prediction using Generalized Elastic Net. PLOS Comput. Biol. 12:3e1004790
    [Google Scholar]
  42. 42. 
    Sokolov A, Paull EO, Stuart JM 2016. One-class detection of cell states in tumor subtypes. Pac. Symp. Biocomput. 21:405–16
    [Google Scholar]
  43. 43. 
    Malta TM, Sokolov A, Gentles AJ, Burzykowski T, Poisson L et al. 2018. Machine learning identifies stemness features associated with oncogenic dedifferentiation. Cell 173:2338–54.e15
    [Google Scholar]
  44. 44. 
    Yang P, Li X-L, Mei J-P, Kwoh C-K, Ng S-K 2012. Positive-unlabeled learning for disease gene identification. Bioinformatics 28:202640–47
    [Google Scholar]
  45. 45. 
    Hu Y, Hase T, Li HP, Prabhakar S, Kitano H et al. 2016. A machine learning approach for the identification of key markers involved in brain development from single-cell transcriptomic data. BMC Genom 17:Suppl. 131025
    [Google Scholar]
  46. 46. 
    Lin C, Jain S, Kim H, Bar-Joseph Z 2017. Using neural networks for reducing the dimensions of single-cell RNA-Seq data. Nucleic Acids Res 45:17e156
    [Google Scholar]
  47. 47. 
    Goodfellow IJ, Pouget-Abadie J, Mirza M, Xu B, Warde-Farley D et al. 2014. Generative adversarial networks. arXiv:1406.2661 [stat.ML]
  48. 48. 
    Bonn S, Machart P, Marouf M, Magruder DS, Bansal V et al. 2018. Realistic in silico generation and augmentation of single cell RNA-seq data using Generative Adversarial Neural Networks. bioRxiv 390153. https://doi.org/10.1101/390153
    [Crossref]
  49. 49. 
    Ghahramani A, Watt FM, Luscombe NM 2018. Generative adversarial networks simulate gene expression and predict perturbations in single cells. bioRxiv 262501. https://doi.org/10.1101/262501
    [Crossref]
  50. 50. 
    van der Maaten L, Postma E, van den Herik J 2009. Dimensionality reduction: a comparative review Tech. Rep. 2009-005, Tilburg Cent. Creat. Comput., Tilburg, Neth .
  51. 51. 
    Engreitz JM, Daigle BJ, Marshall JJ, Altman RB 2010. Independent component analysis: mining microarray data for fundamental human gene expression modules. J. Biomed. Inform. 43:6932–44
    [Google Scholar]
  52. 52. 
    Brunet J-P, Tamayo P, Golub TR, Mesirov JP 2004. Metagenes and molecular pattern discovery using matrix factorization. PNAS 101:124164–69
    [Google Scholar]
  53. 53. 
    Rumelhart DE, Hinton GE, Williams RJ 1986. Learning internal representations by error propagation. Parallel Distributed Processing: Explorations in the Microstructure of Cognition 1 Foundations 318–62 Cambridge, MA: MIT Press
    [Google Scholar]
  54. 54. 
    Weng L. 2018. From autoencoder to beta-VAE. Lil'Log Blog post, Aug. 12. https://lilianweng.github.io/lil-log/2018/08/12/from-autoencoder-to-beta-vae.html
    [Google Scholar]
  55. 55. 
    van der Maaten L, Hinton G 2008. Visualizing data using t-SNE. J. Mach. Learn. Res. 9:Nov.2579–605
    [Google Scholar]
  56. 56. 
    Hoadley KA, Yau C, Wolf DM, Cherniack AD, Tamborero D et al. 2014. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell 158:4929–44
    [Google Scholar]
  57. 57. 
    Kohonen T. 1990. The self-organizing map. Proc. IEEE 78:91464–80
    [Google Scholar]
  58. 58. 
    Chikina M, Zaslavsky E, Sealfon SC 2015. CellCODE: a robust latent variable approach to differential expression analysis for heterogeneous cell populations. Bioinformatics 31:101584–91
    [Google Scholar]
  59. 59. 
    Repsilber D, Kern S, Telaar A, Walzl G, Black GF et al. 2010. Biomarker discovery in heterogeneous tissue samples—taking the in-silico deconfounding approach. BMC Bioinform 11:127
    [Google Scholar]
  60. 60. 
    Gaujoux R, Seoighe C. 2012. Semi-supervised Nonnegative Matrix Factorization for gene expression deconvolution: a case study. Infect. Genet. Evol. 12:5913–21
    [Google Scholar]
  61. 61. 
    Ogundijo OE, Wang X. 2017. A sequential Monte Carlo approach to gene expression deconvolution. PLOS ONE 12:10e0186167
    [Google Scholar]
  62. 62. 
    Tibshirani R, Hastie T, Narasimhan B, Chu G 2002. Diagnosis of multiple cancer types by shrunken centroids of gene expression. PNAS 99:106567–72
    [Google Scholar]
  63. 63. 
    Stuart RO, Wachsman W, Berry CC, Wang-Rodriguez J, Wasserman L et al. 2004. In silico dissection of cell-type-associated patterns of gene expression in prostate cancer. PNAS 101:2615–20
    [Google Scholar]
  64. 64. 
    Amodio M, van Dijk D, Srinivasan K, Chen WS, Mohsen H et al. 2018. Exploring single-cell data with deep multitasking neural networks. bioRxiv 237065. https://doi.org/10.1101/237065
    [Crossref]
  65. 65. 
    Eraslan G, Simon LM, Mircea M, Mueller NS, Theis FJ 2018. Single cell RNA-seq denoising using a deep count autoencoder. bioRxiv 200681. https://doi.org/10.1101/300681
    [Crossref]
  66. 66. 
    Kotliar D, Veres A, Nagy MA, Tabrizi S, Hodis E et al. 2018. Identifying gene expression programs of cell-type identity and cellular activity with single-cell RNA-Seq. bioRxiv 310599. https://doi.org/10.1101/310599
    [Crossref]
  67. 67. 
    Lopez R, Regier J, Cole MB, Jordan M, Yosef N 2018. Deep generative modeling for single-cell transcriptomics. Nat. Methods 15:1053–58
    [Google Scholar]
  68. 68. 
    Stein-O'Brien GL, Clark BS, Sherman T, Zibetti C, Hu Q et al. 2018. Decomposing cell identity for transfer learning across cellular measurements, platforms, tissues, and species. bioRxiv 395004. https://doi.org/10.1101/395004
    [Crossref]
  69. 69. 
    Stumpf PS, MacArthur BD. 2018. Machine learning of stem cell identities from single-cell expression data via regulatory network archetypes. bioRxiv 208470. https://doi.org/10.1101/208470
    [Crossref]
  70. 70. 
    Tarashansky AJ, Xue Y, Quake SR, Wang B 2018. Self-assembling manifolds in single-cell RNA sequencing data. bioRxiv 364166. https://doi.org/10.1101/364166
    [Crossref]
  71. 71. 
    Wolf FA, Angerer P, Theis FJ 2018. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol 19:115
    [Google Scholar]
  72. 72. 
    Grønbech CH, Vording MF, Timshel PN, Sønderby CK, Pers TH, Winther O 2018. scVAE: variational auto-encoders for single-cell gene expression data. bioRxiv 318295. https://doi.org/10.1101/318295
    [Crossref]
  73. 73. 
    Hu Q, Greene CS. 2018. Parameter tuning is a key part of dimensionality reduction via deep variational autoencoders for single cell RNA transcriptomics. bioRxiv 385534. https://doi.org/10.1101/385534
    [Crossref]
  74. 74. 
    DeTomaso D, Jones M, Subramaniam M, Ashuach T, Ye CJ, Yosef N 2018. Functional interpretation of single-cell similarity maps. bioRxiv 403055. https://doi.org/10.1101/403055
    [Crossref]
  75. 75. 
    Fehrmann RSN, Karjalainen JM, Krajewska M, Westra H-J, Maloney D et al. 2015. Gene expression analysis identifies global gene dosage sensitivity in cancer. Nat. Genet. 47:2115–25
    [Google Scholar]
  76. 76. 
    Frigyesi A, Veerla S, Lindgren D, Höglund M 2006. Independent component analysis reveals new and biologically significant structures in micro array data. BMC Bioinform 7:290
    [Google Scholar]
  77. 77. 
    Teschendorff AE, Journée M, Absil PA, Sepulchre R, Caldas C 2007. Elucidating the altered transcriptional programs in breast cancer using independent component analysis. PLOS Comput. Biol. 3:8e161
    [Google Scholar]
  78. 78. 
    Kong W, Vanderburg CR, Gunshin H, Rogers JT, Huang X 2008. A review of independent component analysis application to microarray gene expression data. BioTechniques 45:5501–20
    [Google Scholar]
  79. 79. 
    Li Y, Ngom A. 2013. The non-negative matrix factorization toolbox for biological data mining. Source Code Biol. Med. 8:11–15
    [Google Scholar]
  80. 80. 
    Ochs MF, Fertig EJ. 2012. Matrix factorization for transcriptional regulatory network inference. 2012 IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology (CIBCB)387–96 New York: IEEE
    [Google Scholar]
  81. 81. 
    Stein-O'Brien GL, Arora R, Culhane AC, Favorov AV, Garmire LX et al. 2018. Enter the matrix: Factorization uncovers knowledge from omics. Trends Genet 34:790–805
    [Google Scholar]
  82. 82. 
    Mao W, Harmann B, Sealfon SC, Zaslavsky E, Chikina M 2017. Pathway-Level Information ExtractoR (PLIER) for gene expression data. bioRxiv 116061. https://doi.org/10.1101/116061
    [Crossref]
  83. 83. 
    Taroni JN, Grayson PC, Hu Q, Eddy S, Kretzler M et al. 2018. MultiPLIER: A transfer learning framework reveals systemic features of rare autoimmune disease. bioRxiv 395947. https://doi.org/10.1101/395947
    [Crossref]
  84. 84. 
    Fertig EJ, Ding J, Favorov AV, Parmigiani G, Ochs MF 2010. CoGAPS: an R/C++ package to identify patterns and biological process activity in transcriptomic data. Bioinformatics 26:212792–93
    [Google Scholar]
  85. 85. 
    Tan J, Hammond JH, Hogan DA, Greene CS 2016. ADAGe-based integration of publicly available Pseudomonas aeruginosa gene expression data with denoising autoencoders illuminates microbe-host interactions. mSystems 1:1e00025–15
    [Google Scholar]
  86. 86. 
    Tan J, Doing G, Lewis KA, Price CE, Chen KM et al. 2017. Unsupervised extraction of stable expression signatures from public compendia with an ensemble of neural networks. Cell Syst 5:163–71.e6
    [Google Scholar]
  87. 87. 
    Gupta A, Wang H, Ganapathiraju M 2015. Learning structure in gene expression data using deep architectures, with an application to gene clustering.. bioRxiv 031906. https://doi.org/10.1101/031906
    [Crossref]
  88. 88. 
    Vincent P, Larochelle H, Bengio Y, Manzagol P-A 2008. Extracting and composing robust features with denoising autoencoders. ICML ’08 Proceedings of the 25th International Conference on Machine Learning1096–103 New York: Assoc. Comput. Mach.
    [Google Scholar]
  89. 89. 
    Kingma DP, Welling M. 2013. Auto-encoding variational Bayes. arXiv:1312.6114 [stat.ML]
  90. 90. 
    Rezende DJ, Mohamed S, Wierstra D 2014. Stochastic backpropagation and approximate inference in deep generative models. arXiv:1401.4082 [stat.ML]
  91. 91. 
    Ding J, Condon A, Shah SP 2018. Interpretable dimensionality reduction of single cell transcriptome data with deep generative models. Nat. Commun. 9:1 2002.
    [Google Scholar]
  92. 92. 
    Way GP, Greene CS. 2017. Extracting a biologically relevant latent space from cancer transcriptomes with variational autoencoders. Pac. Symp. Biocomput. 2018:80–91
    [Google Scholar]
  93. 93. 
    Rampasek L, Hidru D, Smirnov P, Haibe-Kains B, Goldenberg A 2017. Dr.VAe: drug response variational autoencoder. arXiv:1706.08203 [stat.ML].
  94. 94. 
    Fabris F, Doherty A, Palmer D, de Magalhães JP, Freitas AA 2018. A new approach for interpreting Random Forest models and its application to the biology of ageing. Bioinformatics 34:142449–56
    [Google Scholar]
  95. 95. 
    Barardo DG, Newby D, Thornton D, Ghafourian T, de Magalhães JP, Freitas AA 2017. Machine learning for predicting lifespan-extending chemical compounds. Aging 9:71721–37
    [Google Scholar]
  96. 96. 
    Guyon I, Weston J, Barnhill S, Vapnik V 2002. Gene selection for cancer classification using support vector machines. Mach. Learn. 46:389–422
    [Google Scholar]
  97. 97. 
    Zhang HH, Ahn J, Lin X, Park C 2006. Gene selection using support vector machines with non-convex penalty. Bioinformatics 22:188–95
    [Google Scholar]
  98. 98. 
    Vanitha CDA, Devaraj D, Venkatesulu M 2015. Gene expression data classification using support vector machine and mutual information-based gene selection. Procedia Comput. Sci. 47:13–21
    [Google Scholar]
  99. 99. 
    Okun O, Priisalu H. 2007. Random forest for gene expression based cancer classification: overlooked issues. Pattern Recognition and Image Analysis J Martí, JM Benedí, AM Mendonça, J Serrat483–90 Berlin: Springer-Verlag
    [Google Scholar]
  100. 100. 
    Chen L, Cai C, Chen V, Lu X 2016. Learning a hierarchical representation of the yeast transcriptomic machinery using an autoencoder model. BMC Bioinform 17:Suppl. 19
    [Google Scholar]
  101. 101. 
    Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL et al. 2005. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. PNAS 102:4315545–50
    [Google Scholar]
  102. 102. 
    Lee S-I, Batzoglou S. 2003. Application of independent component analysis to microarrays. Genome Biol 4:11R76
    [Google Scholar]
  103. 103. 
    Lilliefors HW. 1967. On the Kolmogorov-Smirnov test for normality with mean and variance unknown. J. Am. Stat. Assoc. 62:318399–402
    [Google Scholar]
  104. 104. 
    Wang H, van der Laan MJ 2011. Dimension reduction with gene expression data using targeted variable importance measurement. BMC Bioinform 12:312
    [Google Scholar]
  105. 105. 
    Lukk M, Kapushesky M, Nikkilä J, Parkinson H, Goncalves A et al. 2010. A global map of human gene expression. Nat. Biotechnol. 28:4322–24
    [Google Scholar]
  106. 106. 
    Lenz M, Müller F-J, Zenke M, Schuppert A 2016. Principal components analysis and the reported low intrinsic dimensionality of gene expression microarray data. Sci. Rep. 6:125696
    [Google Scholar]
  107. 107. 
    Zhou W, Altman RB. 2018. Data-driven human transcriptomic modules determined by independent component analysis. BMC Bioinform 19:327
    [Google Scholar]
  108. 108. 
    Cleary B, Cong L, Lander E, Regev A 2017. Composite measurements and molecular compressed sensing for highly efficient transcriptomics. Cell 171:61424–36.e18
    [Google Scholar]
  109. 109. 
    Wu S, Joseph A, Hammonds AS, Celniker SE, Yu B, Frise E 2016. Stability-driven nonnegative matrix factorization to interpret spatial gene expression and build local gene networks. PNAS 113:164290–95
    [Google Scholar]
  110. 110. 
    Gal Y, Ghahramani Z. 2015. Dropout as a Bayesian approximation: representing model uncertainty in deep learning. arXiv:1506.02142 [stat.ML]
  111. 111. 
    Beaulieu-Jones BK, Greene CS. 2017. Reproducibility of computational workflows is automated using continuous analysis. Nat. Biotechnol. 35:4342–46
    [Google Scholar]
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