CRISPR technology: A decade of genome editing is only the beginning

JY Wang, JA Doudna - Science, 2023 - science.org
The advent of clustered regularly interspaced short palindromic repeat (CRISPR) genome
editing, coupled with advances in computing and imaging capabilities, has initiated a new …

[HTML][HTML] High-content CRISPR screening

C Bock, P Datlinger, F Chardon, MA Coelho… - Nature Reviews …, 2022 - nature.com
CRISPR screens are a powerful source of biological discovery, enabling the unbiased
interrogation of gene function in a wide range of applications and species. In pooled …

Accurate proteome-wide missense variant effect prediction with AlphaMissense

J Cheng, G Novati, J Pan, C Bycroft, A Žemgulytė… - Science, 2023 - science.org
The vast majority of missense variants observed in the human genome are of unknown
clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on …

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 …

Loss-of-function, gain-of-function and dominant-negative mutations have profoundly different effects on protein structure

L Gerasimavicius, BJ Livesey, JA Marsh - Nature communications, 2022 - nature.com
Most known pathogenic mutations occur in protein-coding regions of DNA and change the
way proteins are made. Taking protein structure into account has therefore provided great …

Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways

K Watanabe, PR Jansen, JE Savage, P Nandakumar… - Nature …, 2022 - nature.com
Insomnia is a heritable, highly prevalent sleep disorder for which no sufficient treatment
currently exists. Previous genome-wide association studies with up to 1.3 million subjects …

High-yield genome engineering in primary cells using a hybrid ssDNA repair template and small-molecule cocktails

BR Shy, VS Vykunta, A Ha, A Talbot, TL Roth… - Nature …, 2023 - nature.com
Enhancing CRISPR-mediated site-specific transgene insertion efficiency by homology-
directed repair (HDR) using high concentrations of double-stranded DNA (dsDNA) with …

Learning the protein language: Evolution, structure, and function

T Bepler, B Berger - Cell systems, 2021 - cell.com
Language models have recently emerged as a powerful machine-learning approach for
distilling information from massive protein sequence databases. From readily available …

A new era in functional genomics screens

L Przybyla, LA Gilbert - Nature Reviews Genetics, 2022 - nature.com
The past 25 years of genomics research first revealed which genes are encoded by the
human genome and then a detailed catalogue of human genome variation associated with …

Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions

AC Fahed, M Wang, JR Homburger, AP Patel… - Nature …, 2020 - nature.com
Genetic variation can predispose to disease both through (i) monogenic risk variants that
disrupt a physiologic pathway with large effect on disease and (ii) polygenic risk that …