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Detection of Combinatorial Mutational Patterns in Human Cancer Genomes by Exclusivity Analysis

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Cancer Systems Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1711))

Abstract

Cancer genes may tend to mutate in a co-mutational or mutually exclusive manner in a tumor sample of a specific cancer, which constitute two known combinatorial mutational patterns for a given gene set. Previous studies have established that genes functioning in different signaling pathways can mutate in the same sample, i.e., a tumor from one patient, while genes operating in the same pathway are rarely mutated in the same cancer genome. Therefore, reliable identification of combinatorial mutational patterns of candidate cancer genes has important ramifications in inferring signaling network modules in a particular cancer type. While algorithms for discovering mutated driver pathways based on mutual exclusivity of mutations in cancer genes have been proposed, a systematic pipeline for identifying both co-mutational and mutually exclusive patterns with rational significance estimation is still lacking. Here, we describe a reliable framework with detailed procedures to simultaneously explore both combinatorial mutational patterns from public cross-sectional gene mutation data.

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References

  1. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70. https://doi.org/10.1016/S0092-8674(00)81683-9

    Article  CAS  PubMed  Google Scholar 

  2. Stratton MR, Campbell PJ, Futreal PA (2009) The cancer genome. Nature 458(7239):719–724. https://doi.org/10.1038/Nature07943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Peng H, Tan H, Zhao W, Jin G, Sharma S, Xing F, Watabe K, Zhou X (2016) Computational systems biology in cancer brain metastasis. Front Biosci 8:169–186

    Article  Google Scholar 

  4. Tan H, Bao J, Zhou X (2012) A novel missense-mutation-related feature extraction scheme for ‘driver’ mutation identification. Bioinformatics 28(22):2948–2955. https://doi.org/10.1093/bioinformatics/bts558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Tan H, Bao J, Zhou X (2015) Genome-wide mutational spectra analysis reveals significant cancer-specific heterogeneity. Sci Rep 5:12566. https://doi.org/10.1038/srep12566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tan H, Li F, Singh J, Xia X, Cridebring D, Yang J, Bao J, Ma J, Zhan M, Wong STC (2012) A 3-dimentional multiscale model to simulate tumor progression in response to interactions between cancer stem cells and tumor microenvironmental factors. IEEE 6th International Conference on Systems Biology (ISB):297–303. https://doi.org/10.1109/ISB.2012.6314153

  7. Tan H, Wei K, Bao J, Zhou X (2013) In silico study on multidrug resistance conferred by I223R/H275Y double mutant neuraminidase. Mol BioSyst 9(11):2764–2774. https://doi.org/10.1039/c3mb70253g

    Article  CAS  PubMed  Google Scholar 

  8. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW (2013) Cancer genome landscapes. Science 339(6127):1546–1558. https://doi.org/10.1126/science.1235122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10(8):789–799. https://doi.org/10.1038/nm1087

    Article  CAS  PubMed  Google Scholar 

  10. Yeang CH, McCormick F, Levine A (2008) Combinatorial patterns of somatic gene mutations in cancer. FASEB J 22(8):2605–2622. https://doi.org/10.1096/fj.08-108985

    Article  CAS  PubMed  Google Scholar 

  11. Ciriello G, Cerami E, Sander C, Schultz N (2012) Mutual exclusivity analysis identifies oncogenic network modules. Genome Res 22(2):398–406. https://doi.org/10.1101/gr.125567.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vandin F, Upfal E, Raphael BJ (2012) De novo discovery of mutated driver pathways in cancer. Genome Res 22(2):375–385. https://doi.org/10.1101/gr.120477.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Leiserson MD, Blokh D, Sharan R, Raphael BJ (2013) Simultaneous identification of multiple driver pathways in cancer. PLoS Comput Biol 9(5):e1003054. https://doi.org/10.1371/journal.pcbi.1003054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Forbes SA, Beare D, Gunasekaran P, Leung K, Bindal N, Boutselakis H, Ding M, Bamford S, Cole C, Ward S, Kok CY, Jia M, De T, Teague JW, Stratton MR, McDermott U, Campbell PJ (2015) COSMIC: exploring the world’s knowledge of somatic mutations in human cancer. Nucleic Acids Res 43(Database issue):D805–D811. https://doi.org/10.1093/nar/gku1075

    Article  CAS  PubMed  Google Scholar 

  15. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O’Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR (2007) Patterns of somatic mutation in human cancer genomes. Nature 446(7132):153–158. https://doi.org/10.1038/nature05610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ihaka P, Gentleman R (1996) R: a language for data analysis and graphics. J Comput Graph Stat 5(3):299–314

    Google Scholar 

  17. Dempster AP, Laird NM, Rubin DB (1977) Maximum likelihood from incomplete data via EM Algorithm. J Roy Stat Soc B Met 39(1):1–38

    Google Scholar 

  18. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504. https://doi.org/10.1101/gr.1239303. 13/11/2498 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was partially supported by the Beijing Normal University youth funding (105502GK and 2013YB43 to H.T.) and National Institutes of Health (1U01CA166886, 1R01LM010185, and 1U01HL111560 to X.Z.).

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Authors and Affiliations

  1. Department of Radiology, Wake Forest School of Medicine, Center for Bioinformatics & Systems Biology, Medical Center Blvd., Winston-Salem, NC, 27157, USA

    Hua Tan & Xiaobo Zhou

Authors
  1. Hua Tan
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  2. Xiaobo Zhou
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Corresponding author

Correspondence to Xiaobo Zhou .

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Editors and Affiliations

  1. NNF Center for Protein Research, University of Copenhagen, Copenhagen, Denmark

    Louise von Stechow

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Tan, H., Zhou, X. (2018). Detection of Combinatorial Mutational Patterns in Human Cancer Genomes by Exclusivity Analysis. In: von Stechow, L. (eds) Cancer Systems Biology. Methods in Molecular Biology, vol 1711. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7493-1_1

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  • DOI: https://doi.org/10.1007/978-1-4939-7493-1_1

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7492-4

  • Online ISBN: 978-1-4939-7493-1

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