title: Characterization of structural variants with single molecule and hybrid sequencing approaches.
abstract: BACKGROUND
  Structural variation is common in human and cancer genomes. High-throughput DNA sequencing has enabled genome-scale surveys of structural variation. However, the short reads produced by these technologies limit the study of complex variants, particularly those involving repetitive regions. Recent 'third-generation' sequencing technologies provide single-molecule templates and longer sequencing reads, but at the cost of higher per-nucleotide error rates.
  
  
  RESULTS
  We present MultiBreak-SV, an algorithm to detect structural variants (SVs) from single molecule sequencing data, paired read sequencing data, or a combination of sequencing data from different platforms. We demonstrate that combining low-coverage third-generation data from Pacific Biosciences (PacBio) with high-coverage paired read data is advantageous on simulated chromosomes. We apply MultiBreak-SV to PacBio data from four human fosmids and show that it detects known SVs with high sensitivity and specificity. Finally, we perform a whole-genome analysis on PacBio data from a complete hydatidiform mole cell line and predict 1002 high-probability SVs, over half of which are confirmed by an Illumina-based assembly.
authors.affiliation: Department of Computer Science, Brown University, RI Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, NY Institute for Genomics and Multiscale Biology, Icahn School of Medicine, Mount Sinai, NY School of Natural Sciences, University of California, Merced, CA Pacific Biosciences, Menlo Park, CA Center for Computational Molecular Biology, Brown University, RI.
authors.forename: Anna
authors.initials: A
authors.lastname: Ritz
authors.affiliation: Department of Computer Science, Brown University, RI Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, NY Institute for Genomics and Multiscale Biology, Icahn School of Medicine, Mount Sinai, NY School of Natural Sciences, University of California, Merced, CA Pacific Biosciences, Menlo Park, CA Center for Computational Molecular Biology, Brown University, RI Department of Computer Science, Brown University, RI Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, NY Institute for Genomics and Multiscale Biology, Icahn School of Medicine, Mount Sinai, NY School of Natural Sciences, University of California, Merced, CA Pacific Biosciences, Menlo Park, CA Center for Computational Molecular Biology, Brown University, RI.
authors.forename: Ali
authors.initials: A
authors.lastname: Bashir
authors.affiliation: Department of Computer Science, Brown University, RI Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, NY Institute for Genomics and Multiscale Biology, Icahn School of Medicine, Mount Sinai, NY School of Natural Sciences, University of California, Merced, CA Pacific Biosciences, Menlo Park, CA Center for Computational Molecular Biology, Brown University, RI.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Sindi
authors.affiliation: Department of Computer Science, Brown University, RI Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, NY Institute for Genomics and Multiscale Biology, Icahn School of Medicine, Mount Sinai, NY School of Natural Sciences, University of California, Merced, CA Pacific Biosciences, Menlo Park, CA Center for Computational Molecular Biology, Brown University, RI.
authors.forename: David
authors.initials: D
authors.lastname: Hsu
authors.affiliation: Department of Computer Science, Brown University, RI Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, NY Institute for Genomics and Multiscale Biology, Icahn School of Medicine, Mount Sinai, NY School of Natural Sciences, University of California, Merced, CA Pacific Biosciences, Menlo Park, CA Center for Computational Molecular Biology, Brown University, RI.
authors.forename: Iman
authors.initials: I
authors.lastname: Hajirasouliha
authors.affiliation: Department of Computer Science, Brown University, RI Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, NY Institute for Genomics and Multiscale Biology, Icahn School of Medicine, Mount Sinai, NY School of Natural Sciences, University of California, Merced, CA Pacific Biosciences, Menlo Park, CA Center for Computational Molecular Biology, Brown University, RI Department of Computer Science, Brown University, RI Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, NY Institute for Genomics and Multiscale Biology, Icahn School of Medicine, Mount Sinai, NY School of Natural Sciences, University of California, Merced, CA Pacific Biosciences, Menlo Park, CA Center for Computational Molecular Biology, Brown University, RI.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Raphael
mesh_terms: D000465:Algorithms; D056914:Genomic Structural Variation; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA / Q000379:methods*; D017384:Sequence Deletion