SvAnna: efficient and accurate pathogenicity prediction of coding and regulatory structural variants in long-read genome sequencing

Daniel Danis; Julius O B Jacobsen; Parithi Balachandran; Qihui Zhu; Feyza Yilmaz; Justin Reese; Matthias Haimel; Gholson J Lyon; Ingo Helbig; Christopher J Mungall; Christine R Beck; Charles Lee; Damian Smedley; Peter N Robinson

doi:10.1186/s13073-022-01046-6

SvAnna: efficient and accurate pathogenicity prediction of coding and regulatory structural variants in long-read genome sequencing

Genome Med. 2022 Apr 28;14(1):44. doi: 10.1186/s13073-022-01046-6.

Authors

Daniel Danis^#¹, Julius O B Jacobsen^#², Parithi Balachandran¹, Qihui Zhu¹, Feyza Yilmaz¹, Justin Reese³, Matthias Haimel^{4

5

6

7}, Gholson J Lyon^{8

9}, Ingo Helbig^{10

11

12

13}, Christopher J Mungall³, Christine R Beck^{1

14

15}, Charles Lee¹, Damian Smedley¹⁶, Peter N Robinson^{17

18}

Affiliations

¹ The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA.
² William Harvey Research Institute, Charterhouse Square, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
³ Division of Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
⁴ Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.
⁵ St. Anna Children's Cancer Research Institute, Vienna, Austria.
⁶ CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
⁷ Present address: Global Computational Biology and Digital Sciences, Boehringer Ingelheim Regional Center Vienna GmbH & Co KG, 1120, Vienna, Austria.
⁸ Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA.
⁹ Biology PhD Program, The Graduate Center, The City University of New York, New York, USA.
¹⁰ Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹¹ The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹² Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹³ Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
¹⁴ Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT, 06032, USA.
¹⁵ Institute for Systems Genomics, University of Connecticut, Storrs, CT, 06269, USA.
¹⁶ William Harvey Research Institute, Charterhouse Square, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK. [email protected].
¹⁷ The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA. [email protected].
¹⁸ Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT, 06032, USA. [email protected].

^# Contributed equally.

Abstract

Structural variants (SVs) are implicated in the etiology of Mendelian diseases but have been systematically underascertained owing to sequencing technology limitations. Long-read sequencing enables comprehensive detection of SVs, but approaches for prioritization of candidate SVs are needed. Structural variant Annotation and analysis (SvAnna) assesses all classes of SVs and their intersection with transcripts and regulatory sequences, relating predicted effects on gene function with clinical phenotype data. SvAnna places 87% of deleterious SVs in the top ten ranks. The interpretable prioritizations offered by SvAnna will facilitate the widespread adoption of long-read sequencing in diagnostic genomics. SvAnna is available at https://github.com/TheJacksonLaboratory/SvAnn a .

Keywords: Long-read sequencing; Structural variant; Whole genome sequencing.

Publication types

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

MeSH terms

Base Sequence
Chromosome Mapping
Genomics*
Humans
Sequence Analysis, DNA
Virulence

Abstract

Publication types

MeSH terms

Grants and funding