Nature - The international collaboration of the Human Cancer Models Initiative presents a comprehensive resource of next-generation cancer models from 2,780 donors with 25 cancer types and...

We generated a genome-scale, genetic interaction network from the analysis of more than 4 million double mutants in the haploid human cell line, HAP1. The network maps ∼90,000 genetic interactions, in...

Faithful DNA replication is essential for genome stability, yet replication forks face constant stress. The Bloom syndrome helicase (BLM) safeguards fork integrity, but excessive BLM activity can itse...

Transcription factors (TFs) bind specific DNA sequences to control gene expression. Modulating TF activity is of considerable therapeutic interest but very few TFs have been successfully drugged. TF D...

An evaluation framework isolates perturbation-specific effects in perturbation datasets.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Xiao et al. use patient-derived rectal cancer organoids to identify that MEK inhibitors enhance radiation sensitivity by downregulating the DNA damage response protein RAD51. They find synergy with combined PARP inhibition in different preclinical models, thereby offering a promising regimen and potential future alternative to conventional chemoradiation in locally advanced rectal cancer.

Nature Communications - CRISPR-Cas9-based screens have allowed the study of gene-drug interactions. Here, the authors develop CRISPR-Cas9 knock-out, activation and repression screens in human...

When RNA polymerase II (RNA Pol II) is inhibited, the inhibition is sensed and signaled to mitochondria, leading to programmed cell death independently of the loss of RNA Pol II transcription activity...

Variant effect prediction remains a key challenge to resolve in precision medicine. Sophisticated computational models that exploit sequence conservation and structure are increasingly successful in t...

Background Experimental data from functional assays have a critical role in interpreting the impact of genetic variants. Assay data must be unambiguously mapped to a reference genome to make it access...

At the Clinical Atlas of Variant Effects meeting (CLAVE meeting, July 2024, Pittsburgh USA), we developed recommendations for a draft atlas that can be realized by 2030, with a focus on empowering gen...