Analyses

Human genetic evidence increases the success rate of drugs from clinical development to approval but we are still far from reaching peak genetic insights to aid the discovery of targets for more effective drugs.

Efficiency roll-off in a wide range of TADF OLEDs is analysed and a figure of merit proposed for materials design to improve efficiency at high brightness, potentially expanding the range of applications of TADF materials.

A study examining how cities can foster well-being and positive mental health in young residents synthesizes opinions from researchers, practitioners, advocates and young people, highlighting factors that policymakers and urban planners should consider.

Analyses of drivers of water stress are used to predict likely trajectories of the Amazon forest system and suggests potential actions that could prevent system collapse.

Evaluation of evidence generated to test 19 proposed policy recommendations and guidance for the future.

Msemburi et al. describe how the World Health Organization has estimated the excess mortality associated with the COVID-19 pandemic, by month and for 2020 and 2021, and analyse their estimates across the WHO member states, with 14.83 million global excess deaths estimated.

Matched Annotation from NCBI and EMBL-EBI (MANE) delivers joint transcript sets from Ensembl/GENCODE and RefSeq for standardizing variant reporting in clinical genomics and research.

A whole-genome alignment of 240 phylogenetically diverse species of eutherian mammal—including 131 previously uncharacterized species—from the Zoonomia Project provides data that support biological discovery, medical research and conservation.

Analysis of predicted loss-of-function variants from 125,748 human exomes and 15,708 whole genomes in the Genome Aggregation Database (gnomAD) provides a roadmap for human ‘knockout’ studies and a guide for future research into disease biology and drug-target selection.

Climate has affected organized armed conflict within countries, and intensifying climate change is estimated to increase future risks of conflict, although other drivers are substantially more influential and the mechanisms of climate–conflict linkages remain uncertain.

The characterization of missense histone mutations that occur across several cancer types provides insight into the potential role of these mutations in altering chromatin structure and potentially contributing to tumour development.

Analysis of 2002–2016 GRACE satellite observations of terrestrial water storage reveals substantial changes in freshwater resources globally, which are driven by natural and anthropogenic climate variability and human activities.

Investing in adolescents as the parents of the next generation is important for the wellbeing of current and future generations.

The large number of small, similarly sized proteins and the small number of heavy RNA molecules that make up a ribosome reduce the time required for reproduction.

Apparently contradictory conclusions regarding the ‘global warming hiatus’ are reconciled, strengthening the current scientific understanding that long-term global warming is extremely likely to be of anthropogenic origin.

Large-scale analyses of the drug sensitivity of cancer cell lines have been previously reported to yield conflicting conclusions; this Analysis uses independently generated data to demonstrate that consistency can be achieved if key laboratory and data analysis practices are considered when future studies are undertaken.

In panels of cancer cell lines analysed for their response to drug libraries, some studies have proposed distinct pharmacological sensitivities for some cell lines while other studies have not seen the same trends; here the data in the Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer are reassessed, and the authors report a stronger degree of concordance between the two data sets than that in a previous study.

There are ∼800 human GPCRs and 16 different Gα proteins; this study revealed the molecular details of Gα activation by GPCRs and suggests that a universal activation mechanism governs Gα activation—the details of this mechanism can explain how the GPCR–Gα system diversified rapidly, while conserving the allosteric activation mechanism.

Competing financial interests. The majority of authors are employees of Genentech Inc. and/or hold stock in Roche.