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Hum Mutat. 2017 Sep;38(9):1051-1063. doi: 10.1002/humu.23293.

Assessing predictions of fitness effects of missense mutations in SUMO-conjugating enzyme UBE2I.

Zhang J1, Kinch LN2, Cong Q1, Weile J3,4,5, Sun S3,4,5, Cote AG3,4,5, Roth FP3,4,5,6, Grishin NV1,2.

Author information

1
Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas.
2
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas.
3
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
4
The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
5
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
6
Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.

Abstract

The exponential growth of genomic variants uncovered by next-generation sequencing necessitates efficient and accurate computational analyses to predict their functional effects. A number of computational methods have been developed for the task, but few unbiased comparisons of their performance are available. To fill the gap, The Critical Assessment of Genome Interpretation (CAGI) comprehensively assesses phenotypic predictions on newly collected experimental datasets. Here, we present the results of the SUMO conjugase challenge where participants were predicting functional effects of missense mutations in human SUMO-conjugating enzyme UBE2I. The performance of the predictors is similar to each other and is far from perfection. Evolutionary information from sequence alignments dominates the success: deleterious mutations at conserved positions and benign mutations at variable positions are accurately predicted. Prediction accuracy of other mutations remains unsatisfactory, and this fast-growing field of research is yet to learn the use of spatial structure information to improve the predictions significantly.

KEYWORDS:

CAGI; SUMO; performance; predictors; substitutions

PMID:
28817247
PMCID:
PMC5746193
DOI:
10.1002/humu.23293
[Indexed for MEDLINE]
Free PMC Article

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