title: Methods for the detection and assembly of novel sequence in high-throughput sequencing data.
abstract: BACKGROUND
  Large insertions of novel sequence are an important type of structural variants. Previous studies used traditional de novo assemblers for assembling non-mapping high-throughput sequencing (HTS) or capillary reads and then tried to anchor them in the reference using paired read information.
  
  
  RESULTS
  We present approaches for detecting insertion breakpoints and targeted assembly of large insertions from HTS paired data: BASIL and ANISE. On near identity repeats that are hard for assemblers, ANISE employs a repeat resolution step. This results in far better reconstructions than obtained by the compared methods. On simulated data, we found our insert assembler to be competitive with the de novo assemblers ABYSS and SGA while yielding already anchored inserted sequence as opposed to unanchored contigs as from ABYSS/SGA. On real-world data, we detected novel sequence in a human individual and thoroughly validated the assembled sequence. ANISE was found to be superior to the competing tool MindTheGap on both simulated and real-world data.
  
  
  METHODS
  ANISE and BASIL are available for download at http://www.seqan.de/projects/herbarium under a permissive open source license.
authors: Department of Computer Science, Freie Universität Berlin and Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: Manuel
authors: M
authors: Holtgrewe
authors: Department of Computer Science, Freie Universität Berlin and Max Planck Institute for Molecular Genetics, Berlin, Germany Department of Computer Science, Freie Universität Berlin and Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: Leon
authors: L
authors: Kuchenbecker
authors: Department of Computer Science, Freie Universität Berlin and Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: Knut
authors: K
authors: Reinert
mesh_terms: D019295:Computational Biology / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software