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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.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

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.

Genetic association studies for rare variants suffer from lack of power and thus there is a need for methods to improve rare variant discovery. Here, the authors present functionally informed association tests with increased statistical power to aid discovery and interpretation of rare variants.

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

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.

Dire wolves split from living canids around 5.7 million years ago and originated in the New World isolated from the ancestors of grey wolves and coyotes, which evolved in Eurasia and colonized North America only relatively recently.

Sepsis may promptly develop into lethal organ failure, so early diagnosis and treatment planning are essential. Here the authors use machine learning to develop a six-gene signature, termed Sepset, for initial diagnosis, and integrate Sepset into a microfluidic-based bench-side platform for predicting the prognosis of suspected sepsis suitable for the clinic.

Field photographs are essential for research and conservation, but are difficult to access since there is no central database or connection between archives. The 25 leading databases hold only 53% of the plant species of the Americas, illustrating the need for increased work on collecting and standardizing this valuable data.

Authors have previously reported on the efficacy and safety of the recombinant spike protein nanoparticle vaccine, NVX-CoV2373, in healthy adults. In this work, they assess anti-spike binding IgG, anti-RBD binding IgG and neutralising antibody titer as correlates of risk and protection against COVID-19.

Skyrmions - nanoscale, topological spin textures - are promising elements for next-generation computing due to their efficient coupling to currents in racetrack devices. Here, Tan et al. examine over 20,000 instances of current induced skyrmion motion to unveil a comprehensive picture of skyrmion dynamics across currents and fields.

Sports-related concussion is increasingly recognized as a potential danger to paediatric populations, but its short-term and long-term consequences remain poorly understood. This Expert Consensus Document is the result of a 1-day meeting convened by Safe Kids Worldwide, the Alzheimer's Drug Discovery Foundation, and the Andrews Institute for Orthopaedics and Sports Medicine, with the aim of highlighting knowledge gaps and areas of critically needed research in youth sports-related concussion.

Autism spectrum disorder (ASD) is characterized by heterogeneous phenotypes. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, the authors propose a framework to leverage multi-omic datasets and investigate how the GBA influences ASD.

A climatic record from desert speleothems shows that the central Arabian interior experienced recurrent humid intervals over the past 8 million years, which likely facilitated mammalian dispersals between Africa and Eurasia.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Combining gene activation and knockout of different genes in the same cell using two different Cas9 enzymes enables the reconstruction of directional dependency.

This study presents the assembly and analysis of the genome sequence of a female domestic Duroc pig and a comparison with the genomes of wild and domestic pigs from Europe and Asia; the results shed light on the evolutionary relationship between European and Asian wild boars.

The naked mole-rat exhibits extreme longevity, resistance to hypoxia and absence of cardiovascular disease. Here, Faulkes et al. identify mechanisms behind these traits by comparing cardiac metabolomes and transcriptomes of naked more-rats to other African mole-rat genera and evolutionary divergent mammals.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

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.

The relationship of mycorrhizal associations with latitudinal gradients in tree beta-diversity is unexplored. Using a global dataset approach, this study examines how trees with arbuscular mycorrhizal and ectomycorrhizal associations contribute to latitudinal beta-diversity patterns and the environmental controls of these patterns.

Antibody Mediated Prevention (AMP) trials showed that the broadly neutralizing antibody VRC01 could prevent some HIV-1 acquisitions. Here the authors use VRC01 levels and the sensitivity of each acquired HIV virus to predict viral loads in the AMP studies and show that VRC01 influenced viral loads, though potency was lower in vivo than expected.

IgE antibodies targeting cancer antigens can be used for immunotherapy. Here the authors present an IgE antibody targeting the melanoma-associated antigen, chondroitin sulphate proteoglycan 4, that recognises human melanoma, stimulates tumour cell cytotoxicity, and restricts tumour growth in humanised mouse models.

A chemical genetic screen identified inhibitors of an essential transporter from Mycobacterium tuberculosis. Here authors determine atomic structures of EfpA that indicate that it is a lipid transporter, and multiple modes of inhibition that can act synergistically against tuberculosis.

In situ and computational methods are used to investigate the nature of the dense liquid phase of calcium carbonate and its transformation to the amorphous phase that is common in biomineralization processes.

GluA2-lacking AMPA receptors are known to play a role in homeostatic plasticity. Here, the authors show that spiking activity blockade disinhibits mir124 transcription, which in turn suppresses GluA2 mRNA translation, thereby contributing to synaptic upscaling in hippocampal cells.

Two nanobodies that bind SARS-CoV-2 spike RBD are shown to block interaction with receptor ACE2 and thus neutralize the virus, and have an additive effect with antibody CR3022.

Sequence assemblies for the genomes of 16 widely used inbred laboratory mouse strains highlight considerable strain-specific haplotype variation and allow for the identification of regions with the greatest sequence diversity between strains.

Ridges and valleys in many landscapes are uniformly spaced, but no theory has predicted this fundamental topographic wavelength. A characteristic length scale is now derived from equations of mass conservation and sediment transport; it is found to be directly proportional to the valley spacing in models of landform evolution, and to the measured valley spacing at five study sites in the USA.

Frequent dispersal and short-lived local transmission clusters fuelled the 2013–2016 Ebola virus epidemic in Guinea, Liberia and Sierra Leone.

Phyllosilicate minerals are rare in the Noachian-aged crust of the northern lowlands of Mars, compared with the tropical highlands. Geochemical and climate modelling suggest that this dichotomy is consistent with the presence of a cold ocean fringed by cold-based glaciers.

EY6A, a neutralizing antibody isolated from a patient convalescing from COVID-19, binds the receptor binding domain of the SARS-CoV-2 spike glycoprotein with high affinity, at a location away from the binding site for the ACE2 receptor, similar to the one recognized by CR3022.

The Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types; these data were compared with those from human to confirm substantial conservation in the newly annotated potential functional sequences and to reveal pronounced divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.

A digital pathology–artificial intelligence framework that leverages active learning and clinician-in-the-loop real-time feedback improves performance in diagnostic tasks.

The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.

Many island plant species share a syndrome of characteristic phenotype and life history. Cerca et al. find the genomic basis of the plant island syndrome in one of Darwin’s giant daisies, while separating ancestral genomes in a chromosome-resolved polyploid assembly.

Activating the expression of host susceptibility (S) genes is one of the strategies plant pathogens employed to promote infection of their host. Here, the authors show that targeted methylation at the TAL20 effector binding element of the cassava SWEET10a gene lead to resistance to Xanthomonas phaseoli.

Tuberculosis is a major cause of mortality, and the rise of drug-resistant strains of Mycobacterium tuberculosis requires the urgent development of safe and effective treatments. In this work, the authors develop a compound against lysyl-tRNA synthetase, demonstrating on-target mechanism of action and efficacy in vivo.