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The relative importance of the mechanisms underlying species radiation remains unclear. Here, the authors combine reference genome assembly and population genetics analyses to show that neutral forces have contributed to the radiation of the most species-rich tree genus Syzygium.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of Vδ1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission.

Dominic Kwiatkowski and colleagues report a large multicenter genome-wide association study of Plasmodium falciparum resistance to artemisinin. They identify markers of a genetic background on which kelch13 mutations conferring artemisinin resistance are likely to emerge.

TRACERx Lung: Intratumoral transcriptional heterogeneity, which often hinders the development of clinically useful RNA-expression-biased biomarkers for cancer, can now be overcome with an approach for the identification of clonal expression biomarkers.

Genomic profiling of tumours can help tailer treatments to the patient, however, it often fails to accurately predict therapeutic outcomes. Here, the authors combine molecular and functional characterisation via BH3 profiling to identify therapeutically targetable vulnerabilities in glioma.

The neurotransmitters expressed by neurons were thought to be fixed, but recent evidence suggests that during development, and also in the mature nervous system, neurotransmitter expression can be respecified by activity. This respecification seems to have a homeostatic role at synapses and influences behaviour.

Neuroendocrine carcinomas (NECs) arise from different anatomic sites, but have similar histological and clinical features. Here, the authors show that the epigenetic landscape of a range of NECs converges towards a common epigenetic state, while distinct subtypes occur within neuroendocrine prostate cancer contributing to intratumor heterogeneity in clinical samples.

Thousands of recombinant antibodies enriched for specificity against defined targets are assembled in multivalent mixtures with enhanced therapeutic activity.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

The development, characterization and phase I clinical testing of the RAF inhibitor belvarafenib in cancer and a new resistance mechanism mediated by ARAF mutations are described.

There is an unmet medical need for the detection and treatment of early adenomas to prevent their progression to malignant disease. Here the authors show that orally administered E. coli Nissle 1917 can selectively colonize adenomas in mouse models and in patients as a detection tool, as well as deliver immunotherapeutics for colorectal neoplasia treatment.

A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.

A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and potency.

Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.

Multi-ancestry genome-wide association analyses and systematic variant-to-gene mapping strategies implicate new genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Building crystal structures into the electron density is an important step in protein structure solution. Here, the authors recruit online game players, students, and experienced crystallographers to compete in a competition to solve a new structure, and find that crowdsourcing model-building works.

Primary open-angle glaucoma (POAG) leads to progressive vision loss. Here, Choquet et al. perform genome-wide association analysis for POAG in a multi-ethnic cohort, identify a total of nine novel genetic loci and show relevant function of FMNL2 and LMX1B using cell line and mouse experiments.

This study reveals high variability in deforestation emission baselines typically used to derive carbon credits, with median error at 0.778 times the actual rate. It underscores the need for enhanced methods to improve carbon market accuracy and reliability.

This report by the Consortium for Refractive Error and Myopia uses gene-environment-wide interaction study (GEWIS) to identify genetic loci that affect environmental influence in myopia development, and identifies ethnic specific genetic loci that attribute to eye refractive errors.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

Psoriasis is an immune-mediated skin disease with a complex genetic architecture. Here, Elder and colleagues identify 16 novel psoriasis susceptibility loci using GWAS meta-analysis with a combined effective sample size of over 39,000 individuals.

A machine learning approach is presented to identify dominant patterns in disease progression in amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and Parkinson’s disease. The nonlinearity of ALS progression has important clinical implications.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Multi-modal analysis of genomically unstable ovarian tumours characterizes the contribution of anatomical sites and mutational processes to evolutionary phenotypic divergence and immune resistance mechanisms.

How plants respond to multiple stresses occurring simultaneously is poorly understood. Here the authors describe how gene expression in Marchantia polymorpha responds to different combinations of seven abiotic stresses and provide online resources to facilitate data visualization and usability.

A new Burden of Proof meta-analytic method that accounts for between-study heterogeneity and corrects for bias between different study designs is used to interpret the strength of evidence between different pairs of risk factors and health outcomes.

Total mRNA expression in cancer cells is a marker for disease progression and death.

Gene networks evolve by transcription factor (TF) duplication and divergence of their binding site specificities, but little is known about the global constraints at play. Here, the authors study the coevolution of TFs and binding sites using a biophysical-evolutionary approach, and show that the emerging complex fitness landscapes strongly influence regulatory evolution with a role for crosstalk.

Pulmonary venous tumor cells disseminating before tumor resection are heterogeneous, predict relapse and seed future metastasis of lung cancer

Single-cell analysis of genomes from primary human breast tumours and cell lines shows that chromosomal aberrations continue to evolve during primary tumour expansion, resulting in a milieu of subclones within the tumour.

Multi-modal analysis is used to generate a 3D atlas of the upper limb area of the mouse primary motor cortex, providing a framework for future studies of motor control circuitry.

An avalanche photodiode is an opto-electronic amplifier that uses impact ionization to provide enhanced sensitivity at the expense of excess noise. In this manuscript, the authors demonstrate that a small amount of Bismuth (Bi) in Gallium Arsenide (GaAs) avalanche photodiodes significantly reduces this excess noise.

By comparing human induced pluripotent stem cell-derived spinal and ocular motor neurons, the authors identify low levels of a natural 5-lipoxygenase inhibitor in amyotrophic lateral sclerosis (ALS) spinal motor neurons. Functional analogs of 5-lipoxygenase inhibitors can ameliorate in vitro and in vivo ALS phenotypes.

Leveraging enzymatic selectivity, a single reaction stream provides a single diastereomer of the cyclic dinucleotide MK-1454, a promising immune-oncology drug candidate, without the use of protecting groups or chiral auxiliaries.

A phase 1 feasibility trial shows that bilateral deep brain stimulation within the central lateral thalamus can be safely applied and is associated with improved executive control.

The FANTOM4 study identified transcriptional start sites active during proliferation arrest and differentiation of the human monocytic cell line THP-1. Systematic knockdown of 52 transcription factors provide support for their model in which a complex transcriptional network regulates the differentiation process.

Understanding genomic variation in Plasmodium falciparum parasites and inferring migration patterns can guide malaria elimination strategies. Using genome-wide data for 1722 parasites collected from 54 districts, the authors use identity-by-descent approaches to estimate regional parasite migration and spread of artemisinin drug resistance.

Amyotrophic Lateral Sclerosis (ALS) is highly heritable but the mechanisms of sporadic ALS are not fully understood. In this study, the authors identify drivers of variation and disease-relevant changes in the epigenomic profile of iPSC-derived motor neuron lines generated from ALS patients and healthy controls as part of the Answer ALS program.

It is unclear how the T-tubule structure of skeletal muscle, which regulates coordinated muscle contraction, forms. Here, the authors develop a four-dimensional quantitative model for T-tubule formation in zebrafish, based on live imaging, proposing a dynamic endocytic capture model.