Inferring structural variant cancer cell fraction

Cmero, M.; Yuan, K.; Ong, C.S.; Schröder, J.; Adams, D.J.; Anur, P.; Beroukhim, R.; Boutros, P.C.; Bowtell, D.D.L.; Campbell, P.J.; Cao, S.; Christie, E.L.; Cun, Y.; Dawson, K.J.; Demeulemeester, J.; Dentro, S.C.; Deshwar, A.G.; Donmez, N.; Drews, R.M.; Eils, R.; Fan, Y.; Fittall, M.W.; Garsed, D.W.; Gerstung, M.; Getz, G.; Gonzalez, S.; Ha, G.; Haase, K.; Imielinski, M.; Jerman, L.; Ji, Y.; Jolly, C.; Kleinheinz, K.; Lee, J.; Lee-Six, H.; Leshchiner, I.; Livitz, D.; Malikic, S.; Martincorena, I.; Mitchell, T.J.; Morris, Q.D.; Mustonen, V.; Oesper, L.; Peifer, M.; Peto, M.; Raphael, B.J.; Rosebrock, D.; Rubanova, Y.; Sahinalp, S.C.; Salcedo, A.; Schlesner, M.; Schumacher, S.E.; Sengupta, S.; Shi, R.; Shin, S.J.; Spellman, P.T.; Spiro, O.; Stein, L.D.; Tarabichi, M.; Van, Loo P.; Vembu, S.; Vázquez-García, I.; Wang, W.; Wedge, D.C.; Wheeler, D.A.; Wintersinger, J.A.; Yang, T.-P.; Yao, X.; Yu, K.; Zhu, H.; Corcoran, N.M.; Papenfuss, T.; Hovens, C.M.; Markowetz, F.; Macintyre, G.; PCAWG Evolution and Heterogeneity Working Group; PCAWG Consortium

doi:10.1038/s41467-020-14351-8

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Inferring structural variant cancer cell fraction

Cmero, M.;
Yuan, K.;
Ong, C.S.;
Schröder, J.;
Adams, D.J.;
... Shin, S.J.;
외 71명

Citations

SCOPUS

40

초록

We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silico mixtures of real samples, at known proportions, created from two clonal metastases from the same patient. We find that SVclone’s performance is comparable to single-nucleotide variant-based methods, despite having an order of magnitude fewer data points. As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we use SVclone to reveal a subset of liver, ovarian and pancreatic cancers with subclonally enriched copy-number neutral rearrangements that show decreased overall survival. SVclone enables improved characterisation of SV intra-tumour heterogeneity. © 2020, The Author(s).

키워드

cancer; cell; genome; numerical method; performance assessment; ultrastructure; Article; cancer cell fraction; cell fractionation; computer model; copy number variation; gene frequency; gene rearrangement; genetic algorithm; human; liver cancer; molecular cloning; ovary cancer; overall survival; pancreas cancer; single nucleotide polymorphism; SVclone; whole genome sequencing; algorithm; biology; computer simulation; copy number variation; female; genetics; human genome; liver tumor; male; neoplasm; ovary tumor; pancreas tumor; pathology; procedures; prostate tumor; sensitivity and specificity; Algorithms; Computational Biology; Computer Simulation; DNA Copy Number Variations; Female; Gene Frequency; Genome, Human; Humans; Liver Neoplasms; Male; Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms; Prostatic Neoplasms; Sensitivity and Specificity; Whole Genome Sequencing

제목: Inferring structural variant cancer cell fraction

저자: Cmero, M.; Yuan, K.; Ong, C.S.; Schröder, J.; Adams, D.J.; Anur, P.; Beroukhim, R.; Boutros, P.C.; Bowtell, D.D.L.; Campbell, P.J.; Cao, S.; Christie, E.L.; Cun, Y.; Dawson, K.J.; Demeulemeester, J.; Dentro, S.C.; Deshwar, A.G.; Donmez, N.; Drews, R.M.; Eils, R.; Fan, Y.; Fittall, M.W.; Garsed, D.W.; Gerstung, M.; Getz, G.; Gonzalez, S.; Ha, G.; Haase, K.; Imielinski, M.; Jerman, L.; Ji, Y.; Jolly, C.; Kleinheinz, K.; Lee, J.; Lee-Six, H.; Leshchiner, I.; Livitz, D.; Malikic, S.; Martincorena, I.; Mitchell, T.J.; Morris, Q.D.; Mustonen, V.; Oesper, L.; Peifer, M.; Peto, M.; Raphael, B.J.; Rosebrock, D.; Rubanova, Y.; Sahinalp, S.C.; Salcedo, A.; Schlesner, M.; Schumacher, S.E.; Sengupta, S.; Shi, R.; Shin, S.J.; Spellman, P.T.; Spiro, O.; Stein, L.D.; Tarabichi, M.; Van, Loo P.; Vembu, S.; Vázquez-García, I.; Wang, W.; Wedge, D.C.; Wheeler, D.A.; Wintersinger, J.A.; Yang, T.-P.; Yao, X.; Yu, K.; Zhu, H.; Corcoran, N.M.; Papenfuss, T.; Hovens, C.M.; Markowetz, F.; Macintyre, G.; PCAWG Evolution and Heterogeneity Working Group; PCAWG Consortium

DOI: 10.1038/s41467-020-14351-8

발행일: 2020

유형: Article

저널명: Nature Communications

권: 11

호: 1