title: COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples.
abstract: An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis.
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, 135-0064, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: Department of Genome Biology, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Yamanishi
authors.affiliation: Department of Genome Biology, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Kokubu
authors.affiliation: Department of Genome Biology, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Takeda
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, 135-0064, Japan Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, 135-0064, Japan sese.jun@aist.go.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Sese
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D053595:Embryonic Stem Cells / Q000166:cytology*; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*
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