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Performance of computational methods for the evaluation of pericentriolar material 1 missense variants in CAGI‐5
Author(s) -
Monzon Alexander Miguel,
Carraro Marco,
Chiricosta Luigi,
Reggiani Francesco,
Han James,
Ozturk Kivilcim,
Wang Yanran,
Miller Maximilian,
Bromberg Yana,
Capriotti Emidio,
Savojardo Castrense,
Babbi Giulia,
Martelli Pier L.,
Casadio Rita,
Katsonis Panagiotis,
Lichtarge Olivier,
Carter Hannah,
Kousi Maria,
Katsanis Nicholas,
Andreoletti Gaia,
Moult John,
Brenner Steven E.,
Ferrari Carlo,
Leonardi Emanuela,
Tosatto Silvio C. E.
Publication year - 2019
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23856
Subject(s) - missense mutation , biology , genetics , loss function , phenotype , mutation , computational biology , gene
The CAGI‐5 pericentriolar material 1 (PCM1) challenge aimed to predict the effect of 38 transgenic human missense mutations in the PCM1 protein implicated in schizophrenia. Participants were provided with 16 benign variants (negative controls), 10 hypomorphic, and 12 loss of function variants. Six groups participated and were asked to predict the probability of effect and standard deviation associated to each mutation. Here, we present the challenge assessment. Prediction performance was evaluated using different measures to conclude in a final ranking which highlights the strengths and weaknesses of each group. The results show a great variety of predictions where some methods performed significantly better than others. Benign variants played an important role as negative controls, highlighting predictors biased to identify disease phenotypes. The best predictor, Bromberg lab, used a neural‐network‐based method able to discriminate between neutral and non‐neutral single nucleotide polymorphisms. The CAGI‐5 PCM1 challenge allowed us to evaluate the state of the art techniques for interpreting the effect of novel variants for a difficult target protein.