title: Comprehensive characterization of complex structural variations in cancer by directly comparing genome sequence reads.
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.
authors.affiliation: Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain.
authors.forename: Valentí
authors.initials: V
authors.lastname: Moncunill
authors.affiliation: Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain.
authors.forename: Santi
authors.initials: S
authors.lastname: Gonzalez
authors.affiliation: Department of Pathology, Hematopathology Unit, Hospital Clinic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Beà
authors.affiliation: Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain.
authors.forename: Lise O
authors.initials: LO
authors.lastname: Andrieux
authors.affiliation: Department of Pathology, Hematopathology Unit, Hospital Clinic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Salaverria
authors.affiliation: Department of Pathology, Hematopathology Unit, Hospital Clinic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Royo
authors.affiliation: Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Martinez
authors.affiliation: 1] Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain. [2] Computational Bioinformatics, National Institute of Bioinformatics, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Puiggròs
authors.affiliation: European Molecular Biology Laboratory, Genome Biology Research Unit, Heidelberg, Germany.
authors.forename: Maia
authors.initials: M
authors.lastname: Segura-Wang
authors.affiliation: European Molecular Biology Laboratory, Genome Biology Research Unit, Heidelberg, Germany.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Stütz
authors.affiliation: Department of Pathology, Hematopathology Unit, Hospital Clinic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Navarro
authors.affiliation: 1] Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain. [2] Computational Bioinformatics, National Institute of Bioinformatics, Barcelona, Spain.
authors.forename: Romina
authors.initials: R
authors.lastname: Royo
authors.affiliation: 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.
authors.forename: Josep L
authors.initials: JL
authors.lastname: Gelpí
authors.affiliation: Centro Nacional de Analisis Genomico (CNAG), Barcelona, Spain.
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Gut
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo-IUOPA, Oviedo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otín
authors.affiliation: 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.
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
authors.affiliation: European Molecular Biology Laboratory, Genome Biology Research Unit, Heidelberg, Germany.
authors.forename: Jan O
authors.identifier: 0000000227983794
authors.initials: JO
authors.lastname: Korbel
authors.affiliation: 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.
authors.forename: Elias
authors.identifier: 0000000198509793
authors.initials: E
authors.lastname: Campo
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo-IUOPA, Oviedo, Spain.
authors.forename: Xose S
authors.initials: XS
authors.lastname: Puente
authors.affiliation: 1] Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain. [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Torrents
mesh_terms: D002874:Chromosome Mapping; D014644:Genetic Variation; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D009711:Nucleotides