Supplementary Table 1: a Representative Sample of CNV Callers from WGS Data

Supplementary Table 1: A representative sample of CNV callers from WGS data CNV caller RD PE SR AS Other SVs detected Ref AGE X TDP, INV [1] BIC-Seq X [2] BreakDancer X INV, TRL [3] CLEVER X TDP, INV [4] cn.MOPS X [5] CNVeM X [6] CNVer X X [7] CNVnator X [8] CNVrd2 X [9] CNV-Seq X [10] Cortex X INV [11] CREST X INV, TRL [12] DELLY X X INV, TDP, TRL [13] ERDS X [14] GASV-Pro X X [15] Genome STRiP X [16] GROM-RD X [17] Hydra-Multi X INV [18] JointSLM X [19] LUMPY X X X INV, TDP, TRL [20] Magnolya X [21] mrCaNaVar X TDP [22] NovelSeq X [23] PEMer X INV, TDP, TRL [24] Pindel X [25] PRISM X X TDP, INV [26] RDXplorer X [27] readDepth X [28] SegSeq X [29] Socrates X INV, TDP, TRL [30] SoftSearch X X INV, TDP, TRL [31] SoftSV X X INV, TDP, TRL [32] SVDetect X INV, TDP, TRL [33] SVSeq X X [34] TIGRA X INV, TDP, TRL [35] VariationHunter X INV [36] RD = Read Depth; PE = Paired End Mapping; SR = Split Read; AS = Assembly; INV = Inversion; TDP = Tandem Duplication; TRL = Translocation.

Supplemental References 1. Abyzov A, Gerstein M. AGE: defining breakpoints of genomic structural variants at single- nucleotide resolution, through optimal alignments with gap excision. Bioinformatics. 2011;27(5):595-603. doi:10.1093/bioinformatics/btq713. 2. Xi R, Hadjipanayis AG, Luquette LJ, Kim TM, Lee E, Zhang J et al. Copy number variation detection in whole-genome sequencing data using the Bayesian information criterion. Proc Natl Acad Sci U S A. 2011;108(46):E1128-36. doi:10.1073/pnas.1110574108. 3. Chen K, Wallis JW, McLellan MD, Larson DE, Kalicki JM, Pohl CS et al. BreakDancer: an algorithm for high-resolution mapping of genomic structural variation. Nat Methods. 2009;6(9):677-81. doi:10.1038/nmeth.1363. 4. Marschall T, Costa IG, Canzar S, Bauer M, Klau GW, Schliep A et al. CLEVER: clique- enumerating variant finder. Bioinformatics. 2012;28(22):2875-82. doi:10.1093/bioinformatics/bts566. 5. Klambauer G, Schwarzbauer K, Mayr A, Clevert DA, Mitterecker A, Bodenhofer U et al. cn.MOPS: mixture of Poissons for discovering copy number variations in next-generation sequencing data with a low false discovery rate. Nucleic Acids Res. 2012;40(9):e69. doi:10.1093/nar/gks003. 6. Wang Z, Hormozdiari F, Yang WY, Halperin E, Eskin E. CNVeM: copy number variation detection using uncertainty of read mapping. J Comput Biol. 2013;20(3):224-36. doi:10.1089/cmb.2012.0258. 7. Medvedev P, Fiume M, Dzamba M, Smith T, Brudno M. Detecting copy number variation with mated short reads. Genome Res. 2010;20(11):1613-22. doi:10.1101/gr.106344.110. 8. Abyzov A, Urban AE, Snyder M, Gerstein M. CNVnator: an approach to discover, genotype, and characterize typical and atypical CNVs from family and population genome sequencing. Genome Res. 2011;21(6):974-84. doi:10.1101/gr.114876.110. 9. Nguyen HT, Merriman TR, Black MA. The CNVrd2 package: measurement of copy number at complex loci using high-throughput sequencing data. Front Genet. 2014;5:248. doi:10.3389/fgene.2014.00248. 10. Xie C, Tammi MT. CNV-seq, a new method to detect copy number variation using high- throughput sequencing. BMC Bioinformatics. 2009;10:80. doi:10.1186/1471-2105-10-80. 11. Iqbal Z, Caccamo M, Turner I, Flicek P, McVean G. De novo assembly and genotyping of variants using colored de Bruijn graphs. Nat Genet. 2012;44(2):226-32. doi:10.1038/ng.1028. 12. Wang J, Mullighan CG, Easton J, Roberts S, Heatley SL, Ma J et al. CREST maps somatic structural variation in cancer genomes with base-pair resolution. Nat Methods. 2011;8(8):652- 4. doi:10.1038/nmeth.1628. 13. Rausch T, Zichner T, Schlattl A, Stutz AM, Benes V, Korbel JO. DELLY: structural variant discovery by integrated paired-end and split-read analysis. Bioinformatics. 2012;28(18):i333-i9. doi:10.1093/bioinformatics/bts378. 14. Zhu M, Need AC, Han Y, Ge D, Maia JM, Zhu Q et al. Using ERDS to infer copy-number variants in high-coverage genomes. Am J Hum Genet. 2012;91(3):408-21. doi:10.1016/j.ajhg.2012.07.004. 15. Sindi SS, Onal S, Peng LC, Wu HT, Raphael BJ. An integrative probabilistic model for identification of structural variation in sequencing data. Genome Biol. 2012;13(3):R22. doi:10.1186/gb-2012-13-3-r22. 16. Handsaker RE, Korn JM, Nemesh J, McCarroll SA. Discovery and genotyping of genome structural polymorphism by sequencing on a population scale. Nat Genet. 2011;43(3):269-76. doi:10.1038/ng.768. 17. Smith SD, Kawash JK, Grigoriev A. GROM-RD: resolving genomic biases to improve read depth detection of copy number variants. PeerJ. 2015;3:e836. doi:10.7717/peerj.836. 18. Lindberg MR, Hall IM, Quinlan AR. Population-based structural variation discovery with Hydra-Multi. Bioinformatics. 2015;31(8):1286-9. doi:10.1093/bioinformatics/btu771. 19. Magi A, Benelli M, Yoon S, Roviello F, Torricelli F. Detecting common copy number variants in high-throughput sequencing data by using JointSLM algorithm. Nucleic Acids Res. 2011;39(10):e65. doi:10.1093/nar/gkr068. 20. Layer RM, Chiang C, Quinlan AR, Hall IM. LUMPY: a probabilistic framework for structural variant discovery. Genome Biol. 2014;15(6):R84. doi:10.1186/gb-2014-15-6-r84. 21. Nijkamp JF, van den Broek MA, Geertman JM, Reinders MJ, Daran JM, de Ridder D. De novo detection of copy number variation by co-assembly. Bioinformatics. 2012;28(24):3195-202. doi:10.1093/bioinformatics/bts601. 22. Alkan C, Kidd JM, Marques-Bonet T, Aksay G, Antonacci F, Hormozdiari F et al. Personalized copy number and segmental duplication maps using next-generation sequencing. Nat Genet. 2009;41(10):1061-7. doi:10.1038/ng.437. 23. Hajirasouliha I, Hormozdiari F, Alkan C, Kidd JM, Birol I, Eichler EE et al. Detection and characterization of novel sequence insertions using paired-end next-generation sequencing. Bioinformatics. 2010;26(10):1277-83. doi:10.1093/bioinformatics/btq152. 24. Korbel JO, Abyzov A, Mu XJ, Carriero N, Cayting P, Zhang Z et al. PEMer: a computational framework with simulation-based error models for inferring genomic structural variants from massive paired-end sequencing data. Genome Biol. 2009;10(2):R23. doi:10.1186/gb-2009-10-2- r23. 25. Ye K, Schulz MH, Long Q, Apweiler R, Ning Z. Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics. 2009;25(21):2865-71. doi:10.1093/bioinformatics/btp394. 26. Jiang Y, Wang Y, Brudno M. PRISM: pair-read informed split-read mapping for base-pair level detection of insertion, deletion and structural variants. Bioinformatics. 2012;28(20):2576- 83. doi:10.1093/bioinformatics/bts484. 27. Yoon S, Xuan Z, Makarov V, Ye K, Sebat J. Sensitive and accurate detection of copy number variants using read depth of coverage. Genome Res. 2009;19(9):1586-92. doi:10.1101/gr.092981.109. 28. Miller CA, Hampton O, Coarfa C, Milosavljevic A. ReadDepth: a parallel R package for detecting copy number alterations from short sequencing reads. PLoS One. 2011;6(1):e16327. doi:10.1371/journal.pone.0016327. 29. Chiang DY, Getz G, Jaffe DB, O'Kelly MJ, Zhao X, Carter SL et al. High-resolution mapping of copy-number alterations with massively parallel sequencing. Nat Methods. 2009;6(1):99-103. doi:10.1038/nmeth.1276. 30. Schroder J, Hsu A, Boyle SE, Macintyre G, Cmero M, Tothill RW et al. Socrates: identification of genomic rearrangements in tumour genomes by re-aligning soft clipped reads. Bioinformatics. 2014. doi:10.1093/bioinformatics/btt767. 31. Hart SN, Sarangi V, Moore R, Baheti S, Bhavsar JD, Couch FJ et al. SoftSearch: integration of multiple sequence features to identify breakpoints of structural variations. PLoS One. 2013;8(12):e83356. doi:10.1371/journal.pone.0083356. 32. Bartenhagen C, Dugas M. Robust and exact structural variation detection with paired-end and soft-clipped alignments: SoftSV compared with eight algorithms. Brief Bioinform. 2016;17(1):51-62. doi:10.1093/bib/bbv028. 33. Zeitouni B, Boeva V, Janoueix-Lerosey I, Loeillet S, Legoix-ne P, Nicolas A et al. SVDetect: a tool to identify genomic structural variations from paired-end and mate-pair sequencing data. Bioinformatics. 2010;26(15):1895-6. doi:10.1093/bioinformatics/btq293. 34. Zhang J, Wu Y. SVseq: an approach for detecting exact breakpoints of deletions with low- coverage sequence data. Bioinformatics. 2011;27(23):3228-34. doi:10.1093/bioinformatics/btr563. 35. Chen K, Chen L, Fan X, Wallis J, Ding L, Weinstock G. TIGRA: a targeted iterative graph routing assembler for breakpoint assembly. Genome Res. 2014;24(2):310-7. doi:10.1101/gr.162883.113. 36. Hormozdiari F, Hajirasouliha I, Dao P, Hach F, Yorukoglu D, Alkan C et al. Next-generation VariationHunter: combinatorial algorithms for transposon insertion discovery. Bioinformatics. 2010;26(12):i350-7. doi:10.1093/bioinformatics/btq216.