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In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

Examination of a fossil enteropneust, Spartobranchus tenuis (Walcott, 1911), from the Cambrian-period Burgess Shale shows that they looked similar to modern enteropneusts but lived in tubes, like modern pterobranchs; the findings shed light on the common ancestor of enteropneusts and pterobranchs, and hence the origin of chordates.

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.

Marshall Horwitz, Charles Mullighan, Kenneth Offit and colleagues report the identification of a recurrent germline PAX5 mutation in families with pre–B cell acute lymphoblastic leukemia. They also identify sporadic cases of this leukemia with the same mutation that arose somatically.

This mathematical modelling study projects the dynamics of SARS-CoV-2 in England until the end of 2022 assuming that the Omicron BA.2 sublineage remains dominant. They show that booster vaccination was highly effective in mitigating severe outcomes and that future dynamics will depend greatly on assumptions about waning immunity.

The MuTHER Consortium reports an analysis of the genetics of gene expression in three tissues from approximately 850 mono- and dizygotic twins. They systematically dissect cis and trans genetic effects and estimate non-genetic effects on gene expression.

Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them.

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

The epigenome has been shown to change with age, potentially impacting on ageing-related disease. Here the authors investigate the DNA methylation state of the genomic loci of human tRNA and observe enrichment for age-related DNA hypermethylation at tRNA loci.

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.

Epigenetic clocks can measure biological aging, but the relationship between epigenetic age and other hallmarks of aging is incompletely understood. Here the authors show that epigenetic age is associated with nutrient sensing, mitochondria activity and stem cell depletion but distinct from cellular senescence, telomere attrition and genomic instability.

Evaluations of the UK’s contact tracing programme have shown that it has had limited impact on COVID-19 control. Here, the authors show that with high levels of reporting and adherence, contact tracing could reduce transmission, but it should not be used as the sole control measure.

Compound library screening combined with medicinal chemistry and structural biology approaches enables the development of potent and highly selective cell-permeable small-molecule inhibitors of phosphatidylinositol 3-kinase C2α activity and function.

The Periodic Table of Food Initiative addresses food biomolecular composition information gaps through a standardized, accessible and enabling platform based on analytical tools, data and capacity building. Data from 1,650 foods serve as starting point for demonstrating the capacity of this initiative to contribute to nutrition, health and food systems transformations.

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.

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.

Multi-ancestry genome-wide association analyses for birth weight in 153,781 individuals identified 60 genomic loci in which birth weight and fetal genotype were associated and found an inverse genetic correlation between birth weight and cardiometabolic risk.

Yeast central carbon metabolism has been engineered to achieve a more efficient isoprenoid biosynthesis pathway, an advance that brings commodity-scale production of such compounds a step closer.

The heterodimeric cytokine IL-27 consists of the subunits p28 and EBI3. Hunter and colleagues demonstrate that p28 acting alone can inhibit the signaling of many cytokines by interfering with the common receptor gp130.

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.

A method for 3D differentiation of human pluripotent stem cells yields brain cortical spheroids with functional neurons and astrocytes. The spheroids can be sliced for imaging and electrophysiological studies.

Genetically identical twins provide a valuable resource to identify epigenetic factors associated with complex traits. Here the authors adopt this approach and find that differential methylation of the pain gene TRPA1is associated with pain sensitivity in humans.

An unprecedented number of potentially disruptive therapeutic technologies are under development. Forward-looking policies, incentives and infrastructure are needed to harness these advances to provide effective and globally equitable healthcare.

The study on the role of Proliferation-associated 2G4 in motile cilia formation and synchronized cilia movement offers valuable insights into research on motile cilia-related genetic diseases.

Yuan and colleagues developed an artificial intelligence-based method to derive growth patterns and morphological features from hematoxylin and eosin-stained slides of lung adenocarcinoma samples, for improved tumor grading and patient prognostication.

Whole-exome sequencing reveals that a rare variant of phospholipase D3 (PLD3(V232M)) segregates with Alzheimer’s disease status in two independent families and doubles risk for the disease in case–control series, and that several other PLD3 variants increase risk for Alzheimer’s disease in African Americans and people of European descent.

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.

Fowler's syndrome is a cause of urinary retention in young women that is characterized by an abnormal electromyography reading from the external urethral sphincter. This Review, describing the aetiology, pathogenesis and management of Fowler's syndrome, will serve as a guide for urologists unfamiliar with this rare clinical problem.

Currently, genome-wide methylation studies are limited to using targeted arrays or enrichment to assess large sample sizes. Here, Allum et al. demonstrate MethylC-Capture Sequencing, a cost-effective method for investigating genetic and epigenetic variation.

Whole-exome sequencing of circulating tumor cells enables accurate and powered calling of somatic point mutations.

Gene expression analysis in brain tissue from individuals with and without autism spectrum disorder (ASD) suggests that the transcription factor SOX5 contributes to an ASD-associated reduction in transcriptional differences between brain areas and indicates that common transcriptomic changes occur in different forms of ASD.

Elise Robinson and colleagues present the polygenic transmission disequilibrium test (pTDT) for evaluating transmission of polygenic risk in family-based study designs. The authors apply pTDT to a cohort of autism spectrum disorder (ASD) families and find that common polygenic variation acts additively with de novo variants to contribute to ASD risk.

Community building should be integrated into the graduate classroom to foster the development of a professional identity and build connections between students and faculty.