Discovery and quality analysis of a comprehensive set of structural variants and short tandem repeats

David Jakubosky; Erin N Smith; Matteo D'Antonio; Marc Jan Bonder; William W Young Greenwald; Agnieszka D'Antonio-Chronowska; Hiroko Matsui; i2QTL Consortium; Oliver Stegle; Stephen B Montgomery; Christopher DeBoever; Kelly A Frazer

doi:10.1038/s41467-020-16481-5

Discovery and quality analysis of a comprehensive set of structural variants and short tandem repeats

Nat Commun. 2020 Jun 10;11(1):2928. doi: 10.1038/s41467-020-16481-5.

Authors

David Jakubosky^{1

2}, Erin N Smith³, Matteo D'Antonio⁴, Marc Jan Bonder^{5

6}, William W Young Greenwald⁷, Agnieszka D'Antonio-Chronowska⁴, Hiroko Matsui⁴; i2QTL Consortium; Oliver Stegle^{5

6

8}, Stephen B Montgomery^{9

10}, Christopher DeBoever⁴, Kelly A Frazer^{11

12}

Collaborators

i2QTL Consortium:
Marc J Bonder, Na Cai, Ivan Carcamo-Orive, Matteo D'Antonio, Kelly A Frazer, William W Young Greenwald, David Jakubosky, Joshua W Knowles, Hiroko Matsui, Davis J McCarthy, Bogdan A Mirauta, Stephen B Montgomery, Thomas Quertermous, Daniel D Seaton, Craig Smail, Erin N Smith, Oliver Stegle

Affiliations

¹ Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, 92093-0419, USA.
² Department of Biomedical Informatics, University of California San Diego, La Jolla, CA, 92093-0419, USA.
³ Department of Pediatrics, University of California San Diego, La Jolla, CA, 92093, USA.
⁴ Institute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.
⁵ European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, UK.
⁶ European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
⁷ Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA, USA.
⁸ Division of Computational Genomics and Systems Genetics, German Cancer Research Center, Heidelberg, Germany.
⁹ Department of Pathology, Stanford University, Stanford, CA, 94305, USA.
¹⁰ Department of Genetics, Stanford University, Stanford, CA, 94305, USA.
¹¹ Department of Pediatrics, University of California San Diego, La Jolla, CA, 92093, USA. kafrazer@health.ucsd.edu.
¹² Institute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA. kafrazer@health.ucsd.edu.

Abstract

Structural variants (SVs) and short tandem repeats (STRs) are important sources of genetic diversity but are not routinely analyzed in genetic studies because they are difficult to accurately identify and genotype. Because SVs and STRs range in size and type, it is necessary to apply multiple algorithms that incorporate different types of evidence from sequencing data and employ complex filtering strategies to discover a comprehensive set of high-quality and reproducible variants. Here we assemble a set of 719 deep whole genome sequencing (WGS) samples (mean 42×) from 477 distinct individuals which we use to discover and genotype a wide spectrum of SV and STR variants using five algorithms. We use 177 unique pairs of genetic replicates to identify factors that affect variant call reproducibility and develop a systematic filtering strategy to create of one of the most complete and well characterized maps of SVs and STRs to date.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Algorithms
Computational Biology
Genotype
Haplotypes / genetics
High-Throughput Nucleotide Sequencing
Humans
Microsatellite Repeats / genetics*
Whole Genome Sequencing / methods*

Abstract

Publication types

MeSH terms

Grants and funding