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Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

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.

Glycosylphosphatidylinositol (GPI) anchors are found on many cell surface proteins but their biosynthesis is not fully understood. Here, the authors identify genes involved in GPI galactosylation and reveal functional connections between GPI processing, glycosphingolipid biosynthesis and ER-associated degradation.

An appreciation of the health benefits conferred by polyunsaturated fatty acid (PUFA) consumption is growing, particularly in the field of cardiovascular disease, the leading cause of death in diabetes mellitus and diabetic nephropathy. In this article, Shapiro and colleagues provide a brief overview of the role of PUFAs in nutrition and metabolism, discuss the evidence which suggests that certain PUFAs reduce the risk of cardiovascular disease, and describe results from studies investigating the effect of specific PUFAs on diabetic nephropathy.

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

The Ups/PRELI family mediates intramitochondrial lipid distribution and synthesis by shuttling phospholipids between both mitochondrial membranes. Here the authors combine X-ray crystallography, MD simulations and yeast genetic screens and identify residues that are important for Ups/PRELI lipid specificity and reveal a dual lipid recognition mechanism in Ups/PRELI family members.

Impaired liver metabolic function is related to mortality in severely malnourished children. Here the authors report a role for the tryptophan-NAD + pathway in reduced hepatic mitochondrial function and liver steatosis in a mouse model of severe malnutrition.

As part of the second phase of Human Microbiome Project, the Multi-Omic Microbiome Study: Pregnancy Initiative presents a community resource to help better understand how microbiome and host profiles change throughout pregnancy as well as to identify new opportunities for assessment of the risk of preterm birth.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

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

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.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Natural products comprised of a macrocycle ring structure have proven their therapeutic applications as antibiotics, immunosuppressants as well as anticancer agents. Despite this, macrocyclic compounds remain under-explored. Terrett and colleagues review the properties and features of current macrocycle drugs, emphasizing the vast potential of synthetic macrocyles in drug discovery.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

Ancestry and socioeconomic factors influence predictable changes in the vaginal microbiome that occur early in pregnancy in women who experience normal term birth.

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.

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.

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 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.

Seronegative healthcare workers with an innate signature of infection preferentially expand pre-existing T cells targeting the conserved replication transcription complex of SARS-CoV-2 in abortive infection.

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.

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.

The heterogeneity of androgen receptor (AR) gene alterations across metastases in prostate cancer remains unresolved. Here, the authors characterise AR genomic complexity across spatially separated lethal metastases from 10 prostate cancer patients and investigate how AR alterations evolve.

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.

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.

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

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.

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.

Atomically dispersed metal catalysts are of increasing importance in many catalytic processes, but clear structural identification is challenging. Here, a general synthesis of metal (nickel, iron and cobalt) single-atom catalysts on nitrogen-doped graphene allows the authors to identify a common structure and furthermore correlate structure with electrocatalytic activity.

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.

To harness the potential of microbiome science across the broad range of relevant disciplines, new approaches to data infrastructure and transdisciplinary collaboration are necessary. The National Microbiome Data Collaborative is a new initiative to support microbiome data exploration and discovery through a collaborative, integrative data science ecosystem.

Ghorani et al. use a multiomics approach to characterize the effect of tumour mutational burden on the differentiation of CD4 and CD8 T cell subpopulations in non-small cell lung cancer.

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.

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

Multiregion spatial histology, exome and transcriptome data from patients with non-small cell lung cancer suggest that cancer subclones from immune cold regions diversify later than subclones from immune hot regions