Large-scale clinical interpretation of genetic variants using evolutionary data and deep learning

J Frazer, P Notin, M Dias, A Gomez, K Brock, Y Gal… - bioRxiv, 2020 - biorxiv.org
Quantifying the pathogenicity of protein variants in human disease-related genes would
have a profound impact on clinical decisions, yet the overwhelming majority (over 98%) of …

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 …

[HTML][HTML] Deep generative modeling of the human proteome reveals over a hundred novel genes involved in rare genetic disorders

R Orenbuch, AW Kollasch, HD Spinner, CA Shearer… - Medrxiv, 2023 - ncbi.nlm.nih.gov
Identifying causal mutations accelerates genetic disease diagnosis, and therapeutic
development. Missense variants present a bottleneck in genetic diagnoses as their effects …

Bayesian models for syndrome-and gene-specific probabilities of novel variant pathogenicity

D Ruklisa, JS Ware, R Walsh, DJ Balding, SA Cook - Genome medicine, 2015 - Springer
Background With the advent of affordable and comprehensive sequencing technologies,
access to molecular genetics for clinical diagnostics and research applications is increasing …

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 …

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 …

3Cnet: pathogenicity prediction of human variants using multitask learning with evolutionary constraints

DG Won, DW Kim, J Woo, K Lee - Bioinformatics, 2021 - academic.oup.com
Motivation Improvements in next-generation sequencing have enabled genome-based
diagnosis for patients with genetic diseases. However, accurate interpretation of human …

Biomedical informatics and machine learning for clinical genomics

JA Diao, IS Kohane, AK Manrai - Human molecular genetics, 2018 - academic.oup.com
While tens of thousands of pathogenic variants are used to inform the many clinical
applications of genomics, there remains limited information on quantitative disease risk for …

DeMAG predicts the effects of variants in clinically actionable genes by integrating structural and evolutionary epistatic features

F Luppino, IA Adzhubei, CA Cassa… - Nature …, 2023 - nature.com
Despite the increasing use of genomic sequencing in clinical practice, the interpretation of
rare genetic variants remains challenging even in well-studied disease genes, resulting in …

Varipred: Enhancing pathogenicity prediction of missense variants using protein language models

W Lin, J Wells, Z Wang, C Orengo, ACR Martin - bioRxiv, 2023 - biorxiv.org
Computational approaches for predicting the pathogenicity of genetic variants have
advanced in recent years. These methods enable researchers to determine the possible …