High-throughput screening articles from across Nature Portfolio

A new engineering strategy for improving the biosynthesis of secondary metabolites in Streptomyces has been developed through the analysis of genes co-evolved with biosynthetic gene clusters. This strategy has been verified in 11 Streptomyces strains to enhance production of 16,385 metabolites, showing potential applications in drug discovery and industrial production.

A comprehensive time series characterization of a mouse model of cholestatic liver injury with spatial enhanced resolution omics sequencing and single-cell RNA sequencing identifies zonal responses to insult, such as cholangiocyte signaling recruiting lipid-associated macrophages.

A Stereo-seq and scRNA-seq atlas of mouse liver in homeostasis and regeneration after partial hepatectomy identifies zonated genes, pathways, cell–cell interactions and gene regulatory networks. Functional validation finds that cooperation between TBL1XR1 and β-catenin activates hepatocyte proliferation.

In an observational study evaluating functional precision medicine in children and adolescents with relapsed or refractory solid and hematologic malignancies, it was feasible to provide personalized treatment recommendations to treating physicians on the basis of genomic profiling and ex vivo drug sensitivity testing within 4 weeks.

The CPJUMP1 Resource comprises Cell Painting images and profiles of 75 million cells treated with hundreds of chemical and genetic perturbations. The dataset enables exploration of their relationships and lays the foundation for the development of advanced methods to match perturbations.

A new engineering strategy for improving the biosynthesis of secondary metabolites in Streptomyces has been developed through the analysis of genes co-evolved with biosynthetic gene clusters. This strategy has been verified in 11 Streptomyces strains to enhance production of 16,385 metabolites, showing potential applications in drug discovery and industrial production.

A study in Nature Genetics identifies many regulators of genome-wide chromatin accessibility and then reports the mechanistic underpinnings for one of the identified transcription factors.

Inhibition of MEIS1–HOXB13 activity by the aminoglycosides neomycin and paromomycin facilitates cardiomyocyte proliferation and heart regeneration.

Reprogramming of the genetic code allows the synthesis of proteins using new building blocks, thus opening the door to the development of a wider variety of medicines and biocatalysts; however, it is currently limited to α-amino acids. A new study has now reported the incorporation of β-linked and α,α-disubstituted monomers into a ribosome-synthesized protein.

We developed a high-content profiling method named vibrational painting (VIBRANT) for single-cell drug response measurements, combining vibrational imaging, multiplexed vibrational probes and machine learning. VIBRANT showed high performance in predicting drug mechanisms of action, discovering novel compounds and assessing drug combinations, demonstrating great promise for phenotypic drug discovery.