We developed PerturbSpace, a novel approach that integrates CRISPR perturbations with spatially hashed single-cell multiomics. This approach enables the first high-throughput, spatially resolved Perturb-seq analysis across complex tissue architecture in vivo.
Here, we present Iteratively Defined Lengths of Inaccessibility (IDLI), a computational method that maps the single-molecule co-occupancy of structurally distinct nucleosomes, subnucleosomes and other protein–DNA interactions through long-read single-molecule footprinting.
Delivering mRNA to specific cell types remains challenging. Recent work opens the possibility of using synthetic RNA transfer pathways to engineer mRNA ‘delivery cells’. These cells could enable targeted editing, reprogramming or elimination of selected cells for therapeutic benefit.
Epigenetic regulation involves the coordinated interplay of diverse proteins. We present COMBINE, a high-throughput platform that tests over 50,000 pairs of epigenetic effector domains up to 2,094 amino acids in length for their ability to modulate endogenous human gene transcription.
Here, we develop a multi-scale screening framework that integrates bulk patient transcriptomics, functional in vivo genetic screening, and single-cell transcriptomic and epigenomic profiling to nominate chromatin organizers that modulate ITH in breast cancer.
To identify strategies to enhance the utility of third-generation bi-steric mTORC1 inhibitors, we performed genome-scale CRISPR interference chemogenomics screens, which revealed that mTORC1 inhibitor-mediated cytostasis leaves cells exquisitely dependent on the lipid peroxide scavenging enzyme GPX4.
ENPP1 has long been linked with metabolic diseases, with the common ENPP1 K173Q variant conferring increased risk for type 2 diabetes. Here, we demonstrate that the K173Q variant has decreased cGAMP hydrolysis activity, suggesting that this loss of enzymatic function could contribute to its pathogenesis.
We introduce BioReason-Pro, the first multimodal reasoning large language model (LLM) for protein function prediction that integrates protein embeddings with biological context to generate structured reasoning traces.
Heterogeneity in cancer gene expression is typically linked to genetic and epigenetic alteration. Here, we systematically measured messenger RNA (mRNA) dynamics across diverse breast cancer models, revealing that mRNA stability substantially shapes gene expression variability.
Here, by charting a high-resolution map of microbiome ageing and its functional consequences throughout the lifespan of mice, we identify a mechanism by which inhibition of gut–brain signalling during ageing results in impaired neuronal activation in the hippocampus and loss of memory encoding.