title: Assessing structural variation in a personal genome-towards a human reference diploid genome.
abstract: BACKGROUND
  Characterizing large genomic variants is essential to expanding the research and clinical applications of genome sequencing. While multiple data types and methods are available to detect these structural variants (SVs), they remain less characterized than smaller variants because of SV diversity, complexity, and size. These challenges are exacerbated by the experimental and computational demands of SV analysis. Here, we characterize the SV content of a personal genome with Parliament, a publicly available consensus SV-calling infrastructure that merges multiple data types and SV detection methods.
  
  
  RESULTS
  We demonstrate Parliament's efficacy via integrated analyses of data from whole-genome array comparative genomic hybridization, short-read next-generation sequencing, long-read (Pacific BioSciences RSII), long-insert (Illumina Nextera), and whole-genome architecture (BioNano Irys) data from the personal genome of a single subject (HS1011). From this genome, Parliament identified 31,007 genomic loci between 100 bp and 1 Mbp that are inconsistent with the hg19 reference assembly. Of these loci, 9,777 are supported as putative SVs by hybrid local assembly, long-read PacBio data, or multi-source heuristics. These SVs span 59 Mbp of the reference genome (1.8%) and include 3,801 events identified only with long-read data. The HS1011 data and complete Parliament infrastructure, including a BAM-to-SV workflow, are available on the cloud-based service DNAnexus.
  
  
  CONCLUSIONS
  HS1011 SV analysis reveals the limits and advantages of multiple sequencing technologies, specifically the impact of long-read SV discovery. With the full Parliament infrastructure, the HS1011 data constitute a public resource for novel SV discovery, software calibration, and personal genome structural variation analysis.
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. english@bcm.edu.
authors.forename: Adam C
authors.initials: AC
authors.lastname: English
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. William.Salerno@bcm.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Salerno
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. Oliver.Hampton@bcm.edu.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Hampton
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. cgonzagaj@gmail.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gonzaga-Jauregui
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. Shruthi.Ambreth@bcm.edu.
authors.forename: Shruthi
authors.initials: S
authors.lastname: Ambreth
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. dritter@bcm.edu.
authors.forename: Deborah I
authors.initials: DI
authors.lastname: Ritter
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. crbeck@bcm.edu.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Beck
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. cdavis@bcm.edu.
authors.forename: Caleb F
authors.initials: CF
authors.lastname: Davis
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. dahdouli@bcm.edu.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Dahdouli
authors.affiliation: DNAnexus, Mountain View, CA, 94040, USA. sma@dnanexus.com.
authors.forename: Singer
authors.initials: S
authors.lastname: Ma
authors.affiliation: DNAnexus, Mountain View, CA, 94040, USA. acarroll@dnanexus.com.
authors.forename: Andrew
authors.initials: A
authors.lastname: Carroll
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. Narayanan.Veeraraghavan@bcm.edu.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Veeraraghavan
authors.affiliation: Spiral Genetics Inc, Seattle, WA, 98117, USA. jeremy@spiralgenetics.com.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Bruestle
authors.affiliation: Spiral Genetics Inc, Seattle, WA, 98117, USA. becky@spiralgenetics.com.
authors.forename: Becky
authors.initials: B
authors.lastname: Drees
authors.affiliation: BioNano Genomics Inc, San Diego, CA, 92121, USA. ahastie@bionanogenomics.com.
authors.forename: Alex
authors.initials: A
authors.lastname: Hastie
authors.affiliation: BioNano Genomics Inc, San Diego, CA, 92121, USA. elam@bionanogenomics.com.
authors.forename: Ernest T
authors.initials: ET
authors.lastname: Lam
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. Simon.White@bcm.edu.
authors.forename: Simon
authors.initials: S
authors.lastname: White
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. Pamela.Mishra@bcm.edu.
authors.forename: Pamela
authors.initials: P
authors.lastname: Mishra
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. mwang@bcm.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. yhan@bcm.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Han
authors.affiliation: Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200438, China. zhangfeng@fudan.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. pawels@bcm.edu.
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. wheeler@bcm.edu.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. wheeler@bcm.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Wheeler
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. jeffrey.reid@regeneron.com.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Reid
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. donnam@bcm.edu.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. donnam@bcm.edu.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. jr13@bcm.edu.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. jr13@bcm.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rogers
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. sabo@bcm.edu.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. sabo@bcm.edu.
authors.forename: Aniko
authors.initials: A
authors.lastname: Sabo
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. kworley@bcm.edu.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. kworley@bcm.edu.
authors.forename: Kim C
authors.initials: KC
authors.lastname: Worley
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. jlupski@bcm.edu.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. jlupski@bcm.edu.|Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA. jlupski@bcm.edu.|Texas Children's Hospital, Houston, TX, 77030, USA. jlupski@bcm.edu.
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. Eric.Boerwinkle@uth.tmc.edu.|Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. Eric.Boerwinkle@uth.tmc.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA. agibbs@bcm.edu.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. agibbs@bcm.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
mesh_terms: D019295:Computational Biology; D030541:Databases, Genetic; D004171:Diploidy; D015894:Genome, Human; D056914:Genomic Structural Variation; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software