title: Discovery of large genomic inversions using long range information.
abstract: Although many algorithms are now available that aim to characterize different classes of structural variation, discovery of balanced rearrangements such as inversions remains an open problem. This is mainly due to the fact that breakpoints of such events typically lie within segmental duplications or common repeats, which reduces the mappability of short reads. The algorithms developed within the 1000 Genomes Project to identify inversions are limited to relatively short inversions, and there are currently no available algorithms to discover large inversions using high throughput sequencing technologies.
  
  
  
  Here we propose a novel algorithm, VALOR, to discover large inversions using new sequencing methods that provide long range information such as 10X Genomics linked-read sequencing, pooled clone sequencing, or other similar technologies that we commonly refer to as long range sequencing. We demonstrate the utility of VALOR using both pooled clone sequencing and 10X Genomics linked-read sequencing generated from the genome of an individual from the HapMap project (NA12878). We also provide a comprehensive comparison of VALOR against several state-of-the-art structural variation discovery algorithms that use whole genome shotgun sequencing data.
  
  
  
  In this paper, we show that VALOR is able to accurately discover all previously identified and experimentally validated large inversions in the same genome with a low false discovery rate. Using VALOR, we also predicted a novel inversion, which we validated using fluorescent in situ hybridization. VALOR is available at https://github.com/BilkentCompGen/VALOR.
authors.affiliation: Department of Computer Engineering, Bilkent University, Bilkent, 06800, Ankara, Turkey.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Eslami Rasekh
authors.affiliation: Department of Biology, University of Bari, Via Orabona 4, 70125, Bari, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Chiatante
authors.affiliation: Department of Biology, University of Bari, Via Orabona 4, 70125, Bari, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Miroballo
authors.affiliation: Benaroya Research Institute, 1201 Ninth Avenue, 98101, Seattle, WA, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Biology, University of Bari, Via Orabona 4, 70125, Bari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Ventura
authors.affiliation: Benaroya Research Institute, 1201 Ninth Avenue, 98101, Seattle, WA, USA.
authors.forename: Chris T
authors.initials: CT
authors.lastname: Amemiya
authors.affiliation: Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, 3720 15th Avenue NE, 98195, Seattle, WA, USA.
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.affiliation: Department of Biology, University of Bari, Via Orabona 4, 70125, Bari, Italy. francesca.antonacci@uniba.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Antonacci
authors.affiliation: Department of Computer Engineering, Bilkent University, Bilkent, 06800, Ankara, Turkey. calkan@cs.bilkent.edu.tr.
authors.forename: Can
authors.identifier: 0000-0002-5443-0706
authors.initials: C
authors.lastname: Alkan
mesh_terms: D000465:Algorithms; D015894:Genome, Human / Q000235:genetics; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D057345:Sequence Inversion / Q000235:genetics*; D000073336:Whole Genome Sequencing
keywords: Inversion; Linked-reads; Long range sequencing; Read clouds; Structural variation