The value of primary transcripts to the clinical and non-clinical genomics community: Survey results and roadmap for improvements.
default transcript
survey
transcript annotation
variant interpretation
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
11
08
2021
received:
21
04
2021
accepted:
13
08
2021
pubmed:
27
8
2021
medline:
24
3
2022
entrez:
26
8
2021
Statut:
ppublish
Résumé
Variant interpretation is dependent on transcript annotation and remains time consuming and challenging. There are major obstacles for historical data reuse and for interpretation of new variants. First, both RefSeq and Ensembl/GENCODE produce transcript sets in common use, but there is currently no easy way to translate between the two. Second, the resources often used for variant interpretation (e.g. ClinVar, gnomAD, UniProt) do not use the same transcript set, nor default transcript or protein sequence. Ensembl ran a survey in 2018 to sample attitudes to choosing one default transcript per locus, and to gather data on reference sequences used by the scientific community. This was publicised on the Ensembl and UCSC genome browsers, by email and on social media. The survey had 788 responses from 32 different countries, the results of which we report here. We present our roadmap to create an effective default set of transcripts for resources, and for reporting interpretation of clinical variants.
Sections du résumé
BACKGROUND
Variant interpretation is dependent on transcript annotation and remains time consuming and challenging. There are major obstacles for historical data reuse and for interpretation of new variants. First, both RefSeq and Ensembl/GENCODE produce transcript sets in common use, but there is currently no easy way to translate between the two. Second, the resources often used for variant interpretation (e.g. ClinVar, gnomAD, UniProt) do not use the same transcript set, nor default transcript or protein sequence.
METHOD
Ensembl ran a survey in 2018 to sample attitudes to choosing one default transcript per locus, and to gather data on reference sequences used by the scientific community. This was publicised on the Ensembl and UCSC genome browsers, by email and on social media.
RESULTS
The survey had 788 responses from 32 different countries, the results of which we report here.
CONCLUSIONS
We present our roadmap to create an effective default set of transcripts for resources, and for reporting interpretation of clinical variants.
Identifiants
pubmed: 34435752
doi: 10.1002/mgg3.1786
pmc: PMC8683622
doi:
Substances chimiques
Biomarkers
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1786Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : U41 HG007234
Pays : United States
Informations de copyright
© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
Références
Nucleic Acids Res. 2021 Jan 8;49(D1):D916-D923
pubmed: 33270111
Nature. 2016 Aug 17;536(7616):285-91
pubmed: 27535533
Genome Res. 2017 May;27(5):849-864
pubmed: 28396521
Hum Genet. 2020 Oct;139(10):1197-1207
pubmed: 32596782
Genome Med. 2010 Apr 15;2(4):24
pubmed: 20398331
Am J Hum Genet. 2009 Apr;84(4):524-33
pubmed: 19344873
Nucleic Acids Res. 2017 Jan 4;45(D1):D626-D634
pubmed: 27899642
Nature. 2014 Mar 27;507(7493):455-461
pubmed: 24670763
Mol Genet Genomic Med. 2021 Dec;9(12):e1786
pubmed: 34435752
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
Hum Mutat. 2016 Jun;37(6):564-9
pubmed: 26931183
Bioinformatics. 2011 Jul 1;27(13):i275-82
pubmed: 21685081
Nucleic Acids Res. 2018 Jan 4;46(D1):D221-D228
pubmed: 29126148
Nucleic Acids Res. 2021 Jan 8;49(D1):D884-D891
pubmed: 33137190
Nucleic Acids Res. 2017 Jan 4;45(D1):D158-D169
pubmed: 27899622
Nucleic Acids Res. 2014 Jan;42(Database issue):D873-8
pubmed: 24285302
Nucleic Acids Res. 2014 Jan;42(Database issue):D980-5
pubmed: 24234437
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45
pubmed: 26553804