A compendium of next-generation patient-derived models for diverse cancers

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...

rdcu.be

A global genetic interaction map of a human cell reveals conserved principles of genetic networks

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...

biorxiv.org

SLX4IP limits replication stress globally and at ALT telomeres - The EMBO Journal

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...

link.springer.com

biorxiv.org

doi.org

TF-MAPS: fast high-resolution functional and allosteric mapping of DNA-binding proteins

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...

biorxiv.org

Systema: a framework for evaluating genetic perturbation response prediction beyond systematic variation - Nature Biotechnology

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

nature.com

Genetic suppression features ABHD18 as a Barth syndrome therapeutic target - Nature

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.

nature.com

Combined MEK and PARP inhibition enhances radiation response in rectal cancer

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.

dlvr.it

Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions

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...

rdcu.be

RNA Pol II inhibition activates cell death independently from the loss of transcription

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...

cell.com

Variant characterization in the intrinsically disordered human proteome

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...

biorxiv.org

Mapping MAVE data for use in human genomics applications - Genome Biology

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...

genomebiology.biomedcentral.com

Atlas of Variant Effects 2030 Roadmap: resolving human variants of uncertain significance

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...

zenodo.org