Comprehensive characterization of complex structural variations in cancer by directly comparing genome sequence reads

被引：63

作者：

Moncunill, Valenti ^{[1
]}

Gonzalez, Santi ^{[1
]}

Bea, Silvia ^{[2
]}

Andrieux, Lise O. ^{[1
]}

Salaverria, Itziar ^{[2
]}

Royo, Cristina ^{[2
]}

Martinez, Laura ^{[1
]}

Puiggros, Montserrat ^{[1
,3
]}

Segura-Wang, Maia

Stuetz, Adrian M. ^{[4
]}

Navarro, Alba ^{[2
]}

Royo, Romina ^{[1
,3
]}

Gelpi, Josep L. ^{[1
,3
,5
]}

Gut, Ivo G. ^{[6
]}

Lopez-Otin, Carlos ^{[7
]}

Orozco, Modesto ^{[1
,5
,8
]}

Korbel, Jan ^{[4
]}

Campo, Elias ^{[2
,9
]}

Puente, Xose S. ^{[7
]}

Torrents, David ^{[1
,9
]}

机构：

[1] Barcelona Supercomp Ctr, Joint IRB BSC Program Computat Biol, Barcelona, Spain

[2] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Dept Pathol,Hematopathol Unit, Barcelona, Spain

[3] Natl Inst Bioinformat, Barcelona, Spain

[4] European Mol Biol Lab, Genome Biol Res Unit, D-69012 Heidelberg, Germany

[5] Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain

[6] CNAG, Barcelona, Spain

[7] Univ Oviedo, IUOPA, Dept Bioquim & Biol Mol, Oviedo, Spain

[8] IRB Barcelona, Barcelona, Spain

[9] ICREA, Barcelona, Spain

来源：

NATURE BIOTECHNOLOGY | 2014年 / 32卷 / 11期

关键词：

PAIRED-END; MUTATIONS; REARRANGEMENTS; LANDSCAPE; EVOLUTION;

D O I：

10.1038/nbt.3027

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The development of high-throughput sequencing technologies has advanced our understanding of cancer. However, characterizing somatic structural variants in tumor genomes is still challenging because current strategies depend on the initial alignment of reads to a reference genome. Here, we describe SMUFIN (somatic mutation finder), a single program that directly compares sequence reads from normal and tumor genomes to accurately identify and characterize a range of somatic sequence variation, from single-nucleotide variants (SNV) to large structural variants at base pair resolution. Performance tests on modeled tumor genomes showed average sensitivity of 92% and 74% for SNVs and structural variants, with specificities of 95% and 91%, respectively. Analyses of aggressive forms of solid and hematological tumors revealed that SMUFIN identifies breakpoints associated with chromothripsis and chromoplexy with high specificity. SMUFIN provides an integrated solution for the accurate, fast and comprehensive characterization of somatic sequence variation in cancer.

引用

页码：1106 / 1112

页数：7

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