title: Discovery, genotyping and characterization of structural variation and novel sequence at single nucleotide resolution from de novo genome assemblies on a population scale.
abstract: BACKGROUND
  Comprehensive recognition of genomic variation in one individual is important for understanding disease and developing personalized medication and treatment. Many tools based on DNA re-sequencing exist for identification of single nucleotide polymorphisms, small insertions and deletions (indels) as well as large deletions. However, these approaches consistently display a substantial bias against the recovery of complex structural variants and novel sequence in individual genomes and do not provide interpretation information such as the annotation of ancestral state and formation mechanism.
  
  
  RESULTS
  We present a novel approach implemented in a single software package, AsmVar, to discover, genotype and characterize different forms of structural variation and novel sequence from population-scale de novo genome assemblies up to nucleotide resolution. Application of AsmVar to several human de novo genome assemblies captures a wide spectrum of structural variants and novel sequences present in the human population in high sensitivity and specificity.
  
  
  CONCLUSIONS
  Our method provides a direct solution for investigating structural variants and novel sequences from de novo genome assemblies, facilitating the construction of population-scale pan-genomes. Our study also highlights the usefulness of the de novo assembly strategy for definition of genome structure.
authors.affiliation: BGI-Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen N, Denmark ; Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Siyang
authors.initials: S
authors.lastname: Liu
authors.affiliation: BGI-Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen N, Denmark ; School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510006 China.
authors.forename: Shujia
authors.initials: S
authors.lastname: Huang
authors.affiliation: BGI-Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen N, Denmark.
authors.forename: Junhua
authors.initials: J
authors.lastname: Rao
authors.affiliation: BGI-Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen N, Denmark.
authors.forename: Weijian
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Krogh
authors.affiliation: BGI-Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen N, Denmark ; Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D014644:Genetic Variation; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D017421:Sequence Analysis / Q000379:methods*; D012984:Software
keywords: Novel sequence; Structural variation; de novo assembly