Inferring the molecular and phenotypic impact of amino acid variants with MutPred2

V Pejaver, J Urresti, J Lugo-Martinez, KA Pagel… - Nature …, 2020 - nature.com
Identifying pathogenic variants and underlying functional alterations is challenging. To this
end, we introduce MutPred2, a tool that improves the prioritization of pathogenic amino acid …

When loss-of-function is loss of function: assessing mutational signatures and impact of loss-of-function genetic variants

KA Pagel, V Pejaver, GN Lin, HJ Nam, M Mort… - …, 2017 - academic.oup.com
Motivation Loss-of-function genetic variants are frequently associated with severe clinical
phenotypes, yet many are present in the genomes of healthy individuals. The available …

Automated inference of molecular mechanisms of disease from amino acid substitutions

B Li, VG Krishnan, ME Mort, F Xin, KK Kamati… - …, 2009 - academic.oup.com
Motivation: Advances in high-throughput genotyping and next generation sequencing have
generated a vast amount of human genetic variation data. Single nucleotide substitutions …

Updated benchmarking of variant effect predictors using deep mutational scanning

BJ Livesey, JA Marsh - Molecular systems biology, 2023 - embopress.org
The assessment of variant effect predictor (VEP) performance is fraught with biases
introduced by benchmarking against clinical observations. In this study, building on our …

Towards precision medicine: advances in computational approaches for the analysis of human variants

TA Peterson, E Doughty, MG Kann - Journal of molecular biology, 2013 - Elsevier
Variations and similarities in our individual genomes are part of our history, our heritage,
and our identity. Some human genomic variants are associated with common traits such as …

The mutation significance cutoff: gene-level thresholds for variant predictions

Y Itan, L Shang, B Boisson, MJ Ciancanelli, JG Markle… - Nature …, 2016 - nature.com
Next-generation sequencing (NGS) identifies about 20,000 variants per exome, of which
only a few may underlie genetic diseases. Variant-level methods such as PolyPhen-2 …

The evaluation of tools used to predict the impact of missense variants is hindered by two types of circularity

DG Grimm, CA Azencott, F Aicheler, U Gieraths… - Human …, 2015 - Wiley Online Library
Prioritizing missense variants for further experimental investigation is a key challenge in
current sequencing studies for exploring complex and Mendelian diseases. A large number …

Disease variant prediction with deep generative models of evolutionary data

J Frazer, P Notin, M Dias, A Gomez, JK Min, K Brock… - Nature, 2021 - nature.com
Quantifying the pathogenicity of protein variants in human disease-related genes would
have a marked effect on clinical decisions, yet the overwhelming majority (over 98%) of …

Cross-protein transfer learning substantially improves disease variant prediction

M Jagota, C Ye, C Albors, R Rastogi, A Koehl… - Genome Biology, 2023 - Springer
Background Genetic variation in the human genome is a major determinant of individual
disease risk, but the vast majority of missense variants have unknown etiological effects …

[HTML][HTML] Improved pathogenicity prediction for rare human missense variants

Y Wu, H Liu, R Li, S Sun, J Weile, FP Roth - The American Journal of …, 2021 - cell.com
The success of personalized genomic medicine depends on our ability to assess the
pathogenicity of rare human variants, including the important class of missense variation …