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PMID: 31856913 Published · epublish English Comparative Study Evaluation Study Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Paragraph: a graph-based structural variant genotyper for short-read sequence data.

Genome biology ·Vol. 20 ·No. 1 ·2019-00-19 ·Pages 291

Chen S, Krusche P, Dolzhenko E, Sherman RM, Petrovski R, Schlesinger F, Kirsche M, Bentley DR, Schatz MC, Sedlazeck FJ, Eberle MA

Abstract

Accurate detection and genotyping of structural variations (SVs) from short-read data is a long-standing area of development in genomics research and clinical sequencing pipelines. We introduce Paragraph, an accurate genotyper that models SVs using sequence graphs and SV annotations. We demonstrate the accuracy of Paragraph on whole-genome sequence data from three samples using long-read SV calls as the truth set, and then apply Paragraph at scale to a cohort of 100 short-read sequenced samples of diverse ancestry. Our analysis shows that Paragraph has better accuracy than other existing genotypers and can be applied to population-scale studies.

Keywords
Population studies Sequence graphs Structural variation Targeted variant calling
MeSH Terms
Genome, Human Genomic Structural Variation Genotyping Techniques Humans
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Chen Sai
Illumina Inc, 5200 Illumina Way, San Diego, CA, USA.
Krusche Peter
Illumina Cambridge Ltd, Chesterford Research Park, Little Chesterford, UK. | Novartis Pharma AG, Basel, Switzerland.
Dolzhenko Egor
Illumina Inc, 5200 Illumina Way, San Diego, CA, USA.
Sherman Rachel M
Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA.
Petrovski Roman
Illumina Cambridge Ltd, Chesterford Research Park, Little Chesterford, UK.
Schlesinger Felix
Illumina Inc, 5200 Illumina Way, San Diego, CA, USA.
Kirsche Melanie
Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA.
Bentley David R
Illumina Cambridge Ltd, Chesterford Research Park, Little Chesterford, UK.
Schatz Michael C
Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA. | Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Sedlazeck Fritz J
Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA.
Eberle Michael A ORCID
Illumina Inc, 5200 Illumina Way, San Diego, CA, USA. [email protected].
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Article Info
Journal
Genome biology
Abbr.
Genome Biol
ISSN
1474-760X
DOI
10.1186/s13059-019-1909-7
Email
[email protected]
Published
2019-00-19
Epub
2019-00-19
Pages
291
Language
English
Region
England
NLM ID
100960660
PMCID
PMC6921448
Subset
IM
Grants
Foundation for the National Institutes of Health · R01-HG006677 · International
Foundation for the National Institutes of Health · UM1-HG008898 · International
External Links
PubMed source DOI: 10.1186/s13059-019-1909-7 PMC Full Text View journal details
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