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Nat Biotechnol. 2014 Nov;32(11):1106-12. doi: 10.1038/nbt.3027. Epub 2014 Oct 26.

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

Author information

1
Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain.
2
Department of Pathology, Hematopathology Unit, Hospital Clinic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
3
1] Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain. [2] Computational Bioinformatics, National Institute of Bioinformatics, Barcelona, Spain.
4
European Molecular Biology Laboratory, Genome Biology Research Unit, Heidelberg, Germany.
5
1] Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain. [2] Computational Bioinformatics, National Institute of Bioinformatics, Barcelona, Spain. [3] Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
6
Centro Nacional de Analisis Genomico (CNAG), Barcelona, Spain.
7
Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo-IUOPA, Oviedo, Spain.
8
1] Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain. [2] Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain. [3] Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
9
1] Department of Pathology, Hematopathology Unit, Hospital Clinic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
10
1] Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain. [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.

Abstract

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.

PMID:
25344728
DOI:
10.1038/nbt.3027
[Indexed for MEDLINE]

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