The DNA damage response (DDR) is a sophisticated network of cellular pathways whose perturbation leads to genome instability and is a key hallmark of oncogenesis. Here, we present data from 32 genome-scale loss-of-function CRISPR interference chemical–genetic screens with inhibitors targeting core constituents of the DDR machinery.
his review summarizes respiratory and fermentative electron acceptors across eukaryotes, focusing on the evolution of anaerobic pathways. We highlight how ancient metabolic strategies have been conserved and modified to support organisms’ adaptation to diverse environmental niches and to sustain biological resilience.
While machine learning models offer potential for predicting transcriptomic effects of perturbation, they currently struggle to generalize across cellular contexts. Here, we introduce State, a machine learning model that predicts perturbation effects while accounting for cellular heterogeneity within and across experiments.
The Virtual Cell Challenge returns in 2026 with a more demanding test of biological generalization: zero-shot prediction across multiple independent cellular contexts. Participants will build models to predict gene knockdown responses in a new Arc-generated dataset comprising unseen cell lines.
Three-dimensional genome organization shapes transcriptional regulation, yet measuring its spatial coordination in situ within intact tissues remains challenging. We present Spatial Hi-C-RNA, a multimodal platform that simultaneously maps genome-wide chromatin contacts and transcriptomes from the same tissue section at near-single-cell resolution.
Hypoxia disrupts mitochondrial respiration and causes reductive stress. To maintain redox homeostasis, mammalian cells divert electrons toward fermentation. While fermentation in mammals typically involves lactate production, we identify the fermentation of branched-chain amino acids as an alternative electron sink activated by hypoxia.
In this case-control study, autoantibodies targeting the transcobalamin receptor (CD320) responsible for cellular transport of vitamin B12 were identified in a portion of individuals with idiopathic myelopathy, especially those whose disease mimicked subacute combined degeneration.
Biological generative models can predict biological functions without task-specific training data but often under-perform specialized models. Here we demonstrate how to provide task-specific information without losing the general knowledge learned during pretraining by using direct preference optimization to align a model to generate stable protein sequences.
Bridge recombinases from the IS110 family of transposons, such as IS621, associate with a bridge RNA (bRNA) to mediate programmable recombination. Here we show that bRNA is weakly expressed from IS621 loci in the E. coli genome and that the IS621 recombinase–bRNA complex mediates excision less efficiently than insertion.
Many important biological functions arise not from single genes but from complex interactions encoded by entire genomes. We report the first generative design of complete bacteriophage genomes using genome language models. We generated viable bacteriophages with target host tropism, using the phage ΦX174 as our design template.