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Wang, Tang and colleagues develop the low-signal signed iterative random forest pipeline to investigate epistasis in the genetic control of cardiac hypertrophy, identifying epistatic variants near CCDC141, IGF1R, TTN and TNKS loci, and show that hypertrophy in induced pluripotent stem cell-derived cardiomyocytes is nonadditively influenced by interactions among CCDC141, TTN and IGF1R.

Venous tumour thrombus can occur within renal cell carcinoma, and can require complex additional surgery and treatment. Here, the authors analyse multiparametric data from patients treated with axitinib and develop a machine learning model to predict neoadjuvant treatment response.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Traditional regulatory T cell (Tregs) assays utilize mixture of purified cell population. Here the authors develop a ‘single cell suppression profiling of human Tregs’ (scSPOT) with 52-marker CyTOF panel, a cell division detection algorithm, and a whole PBMC system to assess Treg suppressive function on all cell types simultaneously.

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

Groundwater-surface water mixing zones link critical ecosystem domains, but attendant microbe-biogeochemistry-hydrology interactions are poorly known. Here, the authors show that groundwater-surface water mixing stimulates respiration, alters carbon composition, and shifts the ecology from stochastic to deterministic.

One hundred and fifty years ago, life was created by electricity ^– or so it was widely reported. The story illustrates the power of the press, and brings to mind more recent episodes in science.

The availability of labelled training data is one of the practical obstacles towards wide application of machine learning models in medicine. Here the authors develop a weakly supervised deep learning model for the classification of aortic malformations using unlabelled cardiac MRI sequences from the UK biobank.

Larval dispersal of clownfish and butterflyfish across a 10,000 km² area was tracked over 2 years, a large enough scale to inform the design of marine reserve networks and test their performance.

Activated memory B cells express a variety of markers. Here, by mass cytometry and CITE-seq, the authors identify differential expression of CD45RB as a marker distinguishing classical and atypical/non-classical memory B cells, with the former being more prominent during sepsis, while the latter being more abundant in COVID-19 infection or vaccination.

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.

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.

Mutational hotspots can determine evolutionary outcomes and make evolution repeatable. Experiments in bacteria reveal that a powerfully deterministic genetic hotspot can be built and broken by a handful of silent mutations, highlighting an underappreciated role for silent genetic variation in determining adaptive outcomes.

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.

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

Despite their extensive use, the absolute dating of tree-ring chronologies has not hitherto been independently validated at the global scale. Here, the identification of distinct ¹⁴C excursions in 484 individual tree rings, enable the authors to confirm the dating of 44 dendrochronologies from five continents.

HFpEF has few effective treatments. Here, the authors show that inhibition of histone deacetylase 6 (HDAC6) with TYA-018 reverses established HFpEF symptoms in mice, comparably to the use of a sodium-glucose cotransporter 2 inhibitor; highlighting HDAC6 as a potential target to treat HFpEF.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Rebecca Fitzgerald and colleagues used genome sequence analyses to study the progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) and found that the majority of recurrently mutated genes in EAC were also mutated in precursor lesions and that only mutations in TP53 and SMAD4 were stage specific.

The Human Microbiome Project Consortium has established a population-scale framework to study a variety of microbial communities that exist throughout the human body, enabling the generation of a range of quality-controlled data as well as community resources.

O’Regan and colleagues use deep-learning cardiac motion analysis in participants of the UK Biobank to measure diastolic functional traits and perform a genome-wide association study to generate insights into the genetic and environmental factors that influence diastolic function.

This study shows that maternal and perinatal obesity cause bronchial and vascular smooth muscle cell proliferation through an IL-6-FoxO1 axis, and favor thereby the emergence of bronchial obstruction and pulmonary hypertension later in life.

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.

Trans-ancestry genome-wide analyses identify multiple loci associated with ascending aortic diameter. A polygenic score constructed from these loci predicted prevalent risk of thoracic aortic aneurysm in independent populations.

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.

Ray Ming, Robert Paull, Qingyi Yu and colleagues report the genome sequences of two cultivated pineapple varieties and one wild pineapple relative. Their analysis supports the use of the pineapple as a reference genome for monocot comparative genomics and provides insight into the evolution of crassulacean acid metabolism photosynthesis.

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.

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.

The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.

The genome of the wild grass Brachypodium distachyon (Brachypodium), a member of the Pooideae subfamily, is sequenced. The Pooideae are one of three subfamilies of grasses that provide the bulk of human nutrition and may become major sources of renewable energy. Availability of the genome sequence should help establish Brachypodium as a model for developing new energy and food crops.

Ashlee Earl and colleagues analyze whole-genome sequences from 5,310 Mycobacterium tuberculosis isolates from five continents. They find that resistance to isoniazid arises before rifampicin resistance across all of the lineages, geographical regions and time periods.

Small cell lung cancer (SCLC) is characterised by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. The authors show that SCLC patients have a rare CTC subset with a vasculogenic mimicry (VM) phenotype, and that VM is associated with worse overall survival, and alters tumour growth, chemotherapy delivery and efficacy.

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.

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.