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The incidence of type 1 diabetes is increasing, potentially implicating non-genetic factors. Here the authors conduct an epigenome-wide association study in disease-discordant twins and find increased DNA methylation variability at genes associated with immune cell metabolism and the cell cycle.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

RMC-7977, a multi-selective RAS(ON) inhibitor, exhibits potent tumour-selective activity in multiple pre-clinical models of pancreatic ductal adenocarcinoma through a combination of pharmacology and oncogene dependence.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Serological analysis and infection outcomes of participants in the multi-center, prospectively enrolled OCTAVE cohort, comprising 2,686 participants with immune-suppressive diseases who recieved two COVID-19 vaccines, reveals specific clinical phenotypes that might benefit from specific COVID-19 therapeutic strategies.

Analysis of whole-genome doubling (WGD) by using cancer sequencing data combined with simulations of tumor evolution suggests that there is negative selection against homozygous loss of essential genes before WGD but not after.

Deep clinical phenotyping at 28–60 days post-discharge of patients who had been hospitalized with COVID-19 and subsequent long-term follow-up with electronic health records reveal evidence of persistent cardio-renal involvement.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

Analysis of high-resolution three-dimensional models of 149 extant bird species reveals contrasting patterns of integration across the avian skeleton for size and shape: element sizes within body regions are strongly modular, but element shapes are less so and have stronger relationships with ecology.

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.

Biodiversity is unevenly distributed across the tree of life, and theoretical work suggests that biological complexity may be influential in forming these patterns. Here, Brinkworth et al. have shown that bird clades with more complex appendicular skeletons tend to have lower extant species richness.

Cathy Laurie and colleagues detect mosaicism for large chromosomal abnormalities in peripheral blood in a subset of healthy individuals. They show that the frequency of such events increases with age and is associated with elevated risk of developing a subsequent hematological cancer.

Knowledge of how climate change will affect temperatures on a regional scale is needed for effective planning and preparedness. This study uses five climate models to investigate regional warming. It shows that warming is nonlinear for doublings of atmospheric CO₂ and that nonlinearity increases with higher CO₂ concentrations.

Sequencing the genomes of two enteropneusts reveals complex genomic organization and developmental innovation in the ancestor of deuterostomes, a group of animals including echinoderms (starfish and their relatives) and chordates (which includes humans).

Aerial and underwater survey data combined with satellite-derived measurements of sea surface temperature over the past two decades show that multiple mass-bleaching events have expanded to encompass virtually all of the Great Barrier Reef.

RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

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.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

ARM-seq enables enhanced sequencing of modified tRNAs and tRNA fragments. Treatment of RNA with the demethylase AlkB prior to reverse transcription removes three ‘hard-stop’ modifications, allowing for discovery of modified tRNA fragments and their precursors by RNA sequencing.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

The aboveground carbon stock of a montane African forest network is comparable to that of a lowland African forest network and two-thirds higher than default values for these montane forests.

Epigenetic information is transmitted from mother to daughter cells through mitosis. Here, the authors isolate native chromosomes from metaphase-arrested cells and perform LC-MS/MS to identify chromosome-bound proteins in pluripotent stem cells during mitosis and reveal that PRC2, DNA methylation and Mecp2 are required to maintain chromosome compaction.

Analyses of in vivo models, cell lines and patient-derived samples show that apolipoprotein B mRNA-editing catalytic subunit 3B (APOBEC3B) not only restrains lung tumor initiation but also that its upregulation is associated with resistance to targeted therapies. This study highlights the complex and context-dependent role of APOBEC3B in lung cancer.

Proteomic research has the potential to provide disease biomarkers to clinical practice and insight into pathological mechanisms. In this Review, Welberry Smith and colleagues present an overview of the state of the art of proteomic analysis applied to the study of kidney diseases and discuss future directions of this research field and likely developments.

High-throughput sequencing of RNA fragments generated from a single-strand RNA-specific nuclease followed by novel computational analysis yields structural insights into noncoding RNA at the transcriptome level.

Maternal genome-wide analyses identify variants associated with gestational duration and preterm delivery. Maternal alleles positively associated with gestational duration exhibit negative fetal effects on birth weight, likely reflecting antagonistic pleiotropy.

In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

Imaging is critically important for the diagnosis and staging of patients with high-risk prostate cancer. While established prostate cancer staging guidelines have increased appropriate use of imaging, underuse for high-risk prostate cancer remains substantial. Several factors affect the utility of initial diagnostic imaging and, in this Review, Bjurlin and colleagues discuss the performance of conventional and emerging imaging modalities for diagnosing and staging high-risk prostate cancer.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.