Assessing predictions on fitness effects of missense variants in calmodulin.
CAGI
calmodulin
disease
missense variants
predictors
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
18
04
2019
revised:
26
06
2019
accepted:
27
06
2019
pubmed:
10
7
2019
medline:
14
3
2020
entrez:
9
7
2019
Statut:
ppublish
Résumé
This paper reports the evaluation of predictions for the "CALM1" challenge in the fifth round of the Critical Assessment of Genome Interpretation held in 2018. In the challenge, the participants were asked to predict effects on yeast growth caused by missense variants of human calmodulin, a highly conserved protein in eukaryotic cells sensing calcium concentration. The performance of predictors implementing different algorithms and methods is similar. Most predictors are able to identify the deleterious or tolerated variants with modest accuracy, with a baseline predictor based purely on sequence conservation slightly outperforming the submitted predictions. Nevertheless, we think that the accuracy of predictions remains far from satisfactory, and the field awaits substantial improvements. The most poorly predicted variants in this round surround functional CALM1 sites that bind calcium or peptide, which suggests that better incorporation of structural analysis may help improve predictions.
Identifiants
pubmed: 31283071
doi: 10.1002/humu.23857
pmc: PMC6744288
mid: NIHMS1039774
doi:
Substances chimiques
CALM1 protein, human
0
Calmodulin
0
Fungal Proteins
0
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1463-1473Subventions
Organisme : NIH HHS
ID : GM127390
Pays : United States
Organisme : NIH HHS
ID : HG004233
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM066099
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM127390
Pays : United States
Organisme : NHGRI NIH HHS
ID : P50 HG004233
Pays : United States
Organisme : NIH HHS
ID : GM066099
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM079656
Pays : United States
Organisme : NIH HHS
ID : GM079656
Pays : United States
Organisme : NIH HHS
ID : HG007346
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061105
Pays : United States
Organisme : The Welch Foundation
ID : I-1505
Pays : International
Organisme : NIH HHS
ID : HG006650
Pays : United States
Organisme : NIH HHS
ID : AG061105
Pays : United States
Organisme : NHGRI NIH HHS
ID : R13 HG006650
Pays : United States
Organisme : NHGRI NIH HHS
ID : U41 HG007346
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM094575
Pays : United States
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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