Identifying driver mutations in sequenced cancer genomes: computational approaches to enable precision medicine

Abstract

High-throughput DNA sequencing is revolutionizing the study of cancer and enabling the measurement of the somatic mutations that drive cancer development. However, the resulting sequencing datasets are large and complex, obscuring the clinically important mutations in a background of errors, noise, and random mutations. Here, we review computational approaches to identify somatic mutations in cancer genome sequences and to distinguish the driver mutations that are responsible for cancer from random, passenger mutations. First, we describe approaches to detect somatic mutations from high-throughput DNA sequencing data, particularly for tumor samples that comprise heterogeneous populations of cells. Next, we review computational approaches that aim to predict driver mutations according to their frequency of occurrence in a cohort of samples, or according to their predicted functional impact on protein sequence or structure. Finally, we review techniques to identify recurrent combinations of somatic mutations, including approaches that examine mutations in known pathways or protein-interaction networks, as well as de novo approaches that identify combinations of mutations according to statistical patterns of mutual exclusivity. These techniques, coupled with advances in high-throughput DNA sequencing, are enabling precision medicine approaches to the diagnosis and treatment of cancer.

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     Ciriello G Cerami E Sander C Schultz N Mutual exclusivity analysis identifies oncogenic network modulesGenome Res2012 22398406

     Not in our library10.1101/gr.125567.111

105. 105.

     Ciriello G Cerami E Aksoy BA Sander C Schultz N Using MEMo to discover mutual exclusivity modules in cancerCurr Protoc Bioinformatics2013 Mar; Chapter 8:Unit 8.17

     Not in our library10.1002/0471250953.bi0817s41

106. 106.

     Yeang CH McCormick F Levine A Combinatorial patterns of somatic gene mutations in cancerFASEB J2008 2226052622

     Not in our library10.1096/fj.08-108985

107. 107.

     Thomas RK Baker AC Debiasi RM Winckler W Laframboise T Lin WM Wang M Feng W Zander T MacConaill L Macconnaill LE Lee JC Nicoletti R Hatton C Goyette M Girard L Majmudar K Ziaugra L Wong KK Gabriel S Beroukhim R Peyton M Barretina J Dutt A Emery C Greulich H Shah K Sasaki H Gazdar A Minna J High-throughput oncogene mutation profiling in human cancerNat Genet2007 39347351

     Not in our library10.1038/ng1975

108. 108.

     Rajagopalan H Bardelli A Lengauer C Kinzler KW Vogelstein B Velculescu VE Tumorigenesis: RAF/RAS oncogenes and mismatch-repair statusNature2002 418934

     Not in our library10.1038/418934a

109. 109.

     Sparks AB Morin PJ Vogelstein B Kinzler KW Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancerCancer Res1998 5811301134

     Not in our library

110. 110.

     Miller CA Settle SH Sulman EP Aldape KD Milosavljevic A Discovering functional modules by identifying recurrent and mutually exclusive mutational patterns in tumorsBMC Med Genomics2011 434

     Not in our library10.1186/1755-8794-4-34

111. 111.

     Vandin F Upfal E Raphael BJ De novo discovery of mutated driver pathways in cancerGenome Res2012 22375385

     Not in our library10.1101/gr.120477.111

112. 112.
     Simultaneous Identification of Multiple Driver Pathways in Cancer · 2013

     No notice
113. 113.

     Parsons DW Wang TL Samuels Y Bardelli A Cummins JM DeLong L Silliman N Ptak J Szabo S Willson JKV Markowitz S Kinzler KW Vogelstein B Lengauer C Velculescu VE Colorectal cancer: mutations in a signalling pathwayNature2005 436792

     Not in our library10.1038/436792a

114. 114.

     Dias-Santagata D Akhavanfard S David SS Vernovsky K Kuhlmann G Boisvert SL Stubbs H McDermott U Settleman J Kwak EL Clark JW Isakoff SJ Sequist LV Engelman JA Lynch TJ Haber DA Louis DN Ellisen LW Borger DR Iafrate AJ Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicineEMBO Mol Med2010 2146158

     Not in our library10.1002/emmm.201000070

115. 115.

     Wagle N Berger MF Davis MJ Blumenstiel B Defelice M Pochanard P Ducar M Van Hummelen P Macconaill LE Hahn WC Meyerson M Gabriel SB Garraway LA High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencingCancer Discov2012 28293

     Not in our library10.1158/2159-8290.cd-11-0184

116. 116.
     Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples · 2009

     Corrected
117. 117.

     Thomas RK Baker AC Debiasi RM Winckler W Laframboise T Lin WM Wang M Feng W Zander T MacConaill L MacConnaill LE Lee JC Nicoletti R Hatton C Goyette M Girard L Majmudar K Ziaugra L Wong KK Gabriel S Beroukhim R Peyton M Barretina J Dutt A Emery C Greulich H Shah K Sasaki H Gazdar A Minna J High-throughput oncogene mutation profiling in human cancerNature Genetics2007 39347351

     Not in our library10.1038/ng1975

118. 118.

     Kim ES Herbst RS Wistuba II Lee JJ Blumenschein GR Tsao A Stewart DJ Hicks ME Erasmus J Gupta S Alden CM Liu S Tang X Khuri FR Tran HT Johnson BE Heymach JV Mao L Fossella F Kies MS Papadimitrakopoulou V Davis SE Lippman SM Hong WK The BATTLE trial: personalizing therapy for lung cancerCancer Discov2011 14453

     Not in our library10.1158/2159-8274.cd-10-0010

119. 119.

     Huang FW Hodis E Xu MJ Kryukov GV Chin L Garraway LA Highly recurrent TERT promoter mutations in human melanomaScience2013 339957959

     Not in our library10.1126/science.1229259

120. 120.

     Dunham I Kundaje A Aldred SF Collins PJ Davis CA Doyle F Epstein CB Frietze S Harrow J Kaul R Khatun J Lajoie BR Landt SG Lee BK Pauli F Rosenbloom KR Sabo P Safi A Sanyal A Shoresh N Simon JM Song L Trinklein ND Altshuler RC Birney E Brown JB Cheng C Djebali S Dong X Ernst J An integrated encyclopedia of DNA elements in the human genomeNature2012 4895774

     Not in our library10.1038/nature11247

121. 121.

     Hofree M Shen JP Carter H Gross A Ideker T Network-based stratification of tumor mutationsNat Methods2013 1011081115

     Not in our library10.1038/nmeth.2651

122. 122.

     Weinstein JN Collisson EA Mills GB Shaw KRM Ozenberger BA Ellrott K Shmulevich I Sander C Stuart JM Cancer Genome Atlas Research NetworkThe Cancer Genome Atlas Pan-Cancer analysis projectNat Genet2013 4511131120

     Not in our library10.1038/ng.2764

123. 123.

     Kandoth C McLellan MD Vandin F Ye K Niu B Lu C Xie M Zhang Q McMichael JF Wyczalkowski MA Leiserson MDM Miller CA Welch JS Walter MJ Wendl MC Ley TJ Wilson RK Raphael BJ Ding L Mutational landscape and significance across 12 major cancer typesNature2013 502333339

     Not in our library10.1038/nature12634

124. 124.

     Ciriello G Miller ML Aksoy BA Senbabaoglu Y Schultz N Sander C Emerging landscape of oncogenic signatures across human cancersNat Genet2013 4511271133

     Not in our library10.1038/ng.2762

125. 125.

     Zack TI Schumacher SE Carter SL Cherniack AD Saksena G Tabak B Lawrence MS Zhang CZ Wala J Mermel CH Sougnez C Gabriel SB Hernandez B Shen H Laird PW Getz G Meyerson M Beroukhim R Pan-cancer patterns of somatic copy number alterationNat Genet2013 4511341140

     Not in our library10.1038/ng.2760

126. 126.

     Vaske CJ Benz SC Sanborn JZ Earl D Szeto C Zhu J Haussler D Stuart JM Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGMBioinformatics2010 26i237i245

     Not in our library10.1093/bioinformatics/btq182

127. 127.

     Paull EO Carlin DE Niepel M Sorger PK Haussler D Stuart JM Discovering causal pathways linking genomic events to transcriptional states using Tied Diffusion Through Interacting Events (TieDIE)Bioinformatics2013 2927572764

     Not in our library10.1093/bioinformatics/btt471

128. 128.

     Roth A Ding J Morin R Crisan A Ha G Giuliany R Bashashati A Hirst M Turashvili G Oloumi A Marra MA Aparicio S Shah SP JointSNVMix: a probabilistic model for accurate detection of somatic mutations in normal/tumour paired next-generation sequencing dataBioinformatics2012 28907913

     Not in our library10.1093/bioinformatics/bts053

129. 129.

     Xi R Luquette J Hadjipanayis A Kim TM Park PJ BIC-seq: a fast algorithm for detection of copy number alterations based on high-throughput sequencing dataGenome Biol2010 11O10

     Not in our library

130. 130.

     Yang L Luquette LJ Gehlenborg N Xi R Haseley PS Hsieh CH Zhang C Ren X Protopopov A Chin L Kucherlapati R Lee C Park PJ Diverse mechanisms of somatic structural variations in human cancer genomesCell2013 153919929

     Not in our library10.1016/j.cell.2013.04.010

131. 131.

     Krumm N Sudmant PH Ko A O’Roak BJ Malig M Coe BP Quinlan AR Nickerson DA Eichler EE NHLBI Exome Sequencing ProjectCopy number variation detection and genotyping from exome sequence dataGenome Res2012 2215251532

     Not in our library10.1101/gr.138115.112

132. 132.

     Chen K Wallis JW McLellan MD Larson DE Kalicki JM Pohl CS McGrath SD Wendl MC Zhang Q Locke DP Shi X Fulton RS Ley TJ Wilson RK Ding L Mardis ER BreakDancer: an algorithm for high-resolution mapping of genomic structural variationNat Methods2009 6677681

     Not in our library10.1038/nmeth.1363

133. 133.

     Hormozdiari F Hajirasouliha I McPherson A Eichler EE Sahinalp SC Simultaneous structural variation discovery among multiple paired-end sequenced genomesGenome Res2011 2122032212

     Not in our library10.1101/gr.120501.111

134. 134.

     Sindi S Helman E Bashir A Raphael BJ A geometric approach for classification and comparison of structural variantsBioinformatics2009 25i222i230

     Not in our library10.1093/bioinformatics/btp208

135. 135.

     Sindi SS Onal S Peng LC Wu HT Raphael BJ An integrative probabilistic model for identification of structural variation in sequencing dataGenome Biol2012 13R22

     Not in our library10.1186/gb-2012-13-3-r22

136. 136.

     Escaramís G Tornador C Bassaganyas L Rabionet R Tubio JMC Martínez-Fundichely A Cáceres M Gut M Ossowski S Estivill X PeSV-Fisher: identification of somatic and non-somatic structural variants using next generation sequencing dataPLoS One2013 8e63377

     Not in our library10.1371/journal.pone.0063377

137. 137.
     DELLY: structural variant discovery by integrated paired-end and split-read analysis · 2012

     No notice
138. 138.

     Drier Y Lawrence MS Carter SL Stewart C Gabriel SB Lander ES Meyerson M Beroukhim R Getz G Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutabilityGenome Res2013 23228235

     Not in our library10.1101/gr.141382.112

139. 139.

     Hua X Xu H Yang Y Zhu J Liu P Lu Y DrGaP: a powerful tool for identifying driver genes and pathways in cancer sequencing studiesAm J Hum Genet2013 93439451

     Not in our library10.1016/j.ajhg.2013.07.003

140. 140.
     Automated Network Analysis Identifies Core Pathways in Glioblastoma · 2010

     No notice

Cited by papers we hold 5

• A systematic review of the applications of artificial intelligence and machine learning in autoimmune diseases · 2020
  No notice
• A novel network regularized matrix decomposition method to detect mutated cancer genes in tumour samples with inter-patient heterogeneity · 2017
  Not checked
• CoMEt: a statistical approach to identify combinations of mutually exclusive alterations in cancer · 2015
  Corrected
• Systematic pan-cancer analysis of tumour purity · 2015
  Corrected
• Review of Current Methods, Applications, and Data Management for the Bioinformatics Analysis of Whole Exome Sequencing · 2014
  Not checked

Reads

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