@article{79eb1479af4b4756a6b5219cb51d50cc,
title = "Assessing predictions on fitness effects of missense variants in calmodulin",
abstract = "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.",
keywords = "CAGI, calmodulin, disease, missense variants, predictors",
author = "Jing Zhang and Kinch, {Lisa N.} and Qian Cong and Panagiotis Katsonis and Olivier Lichtarge and Castrense Savojardo and Giulia Babbi and Martelli, {Pier Luigi} and Emidio Capriotti and Rita Casadio and Aditi Garg and Debnath Pal and Jochen Weile and Song Sun and Marta Verby and Roth, {Frederick P.} and Grishin, {Nick V.}",
note = "Funding Information: The CAGI experiment coordination is supported by NIH U41 HG007346 and the CAGI conference by NIH R13 HG006650. The assessment of this challenge is supported by grants (to NVG) from the National Institutes of Health GM127390 and the Welch Foundation I‐1505. Olivier Lichtarge and Panagiotis Katsonis were supported by the NIH‐GM079656, NIH‐GM066099 grants and NIH‐AG061105. FPR was supported by grants from the Canada Excellence Research Chairs Program, a Canadian Institutes of Health Research Foundation Grant, and by the National Human Genome Research Institute of the NIH Center of Excellence in Genomic Science Initiative (HG004233). Funding Information: The CAGI experiment coordination is supported by NIH U41 HG007346 and the CAGI conference by NIH R13 HG006650. The assessment of this challenge is supported by grants (to NVG) from the National Institutes of Health GM127390 and the Welch Foundation I-1505. Olivier Lichtarge and?Panagiotis Katsonis were supported by the NIH-GM079656, NIH-GM066099 grants and NIH-AG061105. FPR was supported by grants from the Canada Excellence Research Chairs Program, a Canadian Institutes of Health Research Foundation Grant, and by the National Human Genome Research Institute of the NIH Center of Excellence in Genomic Science Initiative (HG004233). Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",
year = "2019",
month = sep,
day = "1",
doi = "10.1002/humu.23857",
language = "English (US)",
volume = "40",
pages = "1463--1473",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "Wiley-Liss Inc.",
number = "9",
}