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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.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

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.

Human activities affect marine predators in complex ways, yet we lack spatial understanding of cumulative impacts across key habitats. Here the authors analyse distribution and movements of eight marine predators, and find that species and human impacts vary across space and overlap within marine sanctuaries.

In a new study including 200 families who experienced perinatal death, adding genomic analyses to standard autopsies improved the identification of underlying pathogenic causes and informed genetic counseling.

Gene discovery and polygenic predictions from a genome-wide association study of educational attainment in 1.1 million individuals.

Here, using clinical samples and autopsy tissues, the authors combine fast-colorimetric test (LAMP) for SARS-CoV-2 infection and large-scale shotgun metatranscriptomics for host, viral, and microbial profiling and provide a map of the viral genetic features of the New York City outbreak and associate specific host responses and gene expression perturbations with SARS-CoV-2 infection.

The components of the tumour microenvironment contribute to prostate cancer initiation and progression. Here the authors perform single-cell RNA sequencing and spatial transcriptomics analysis of prostate cancer stroma from mouse models at different stages of the disease and develop a gene signature to predict distant metastasis in patients.

Providing detailed structural descriptions of the ultrafast photochemical events that occur in light-sensitive proteins is key to their understanding. Now, excited-state structures in the reversibly switchable fluorescent protein rsEGFP2 have been solved by time-resolved crystallography using an X-ray laser. These structures enabled the design of a mutant with improved photoswitching quantum yields.

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.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

The hydroxylase EgIN2 contributes to triple negative breast cancers. Here, using an enzyme-substrate trapping strategy, the authors identify ASDL as a bona fide substrate of EgIN2 promoting aggressive properties of TNBC via the activation of cMYC signaling.

Astroviruses are the leading cause of pediatric diarrhea, but which cells are the main targets in the gut remains unclear. Here, using an in vivo model of murine astrovirus, the authors show that the virus infects goblet cells and that this alters mucus production and increases mucus-associated bacterial communities in the gut.

By interfacing graphene with other materials it is possible to break the intrinsic inversion symmetry and observe interesting quantum transport phenomena. Here, the authors conduct transport measurements of encapsulated graphene at different alignment angles and find evidence of nonlocal resistance above and below 60 K suggesting the existence of a quantum valley Hall state.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Characterizing fission products in uranium dioxide nuclear fuel is important for predicting its long-term properties. Here, machine learning is used to mine microscopy images of precipitates and nanoscale gas bubbles in high-burn-up fuels, providing detailed structural insight of nanoscale fission products.

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

Organoids derived from human intestinal cells that are co-cultured with bacteria carrying the genotoxic pks⁺ island develop a distinct mutational signature associated with colorectal cancer.

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.

The lineage transcription factor PAX8 is shown to play a pivotal part in determining cancer risk in clear cell renal cell carcinoma, providing insights into how genetic mutations lead to specific types of cancer.

X-ray-induced explosions in water drops, examined using time-resolved imaging, show interacting high-speed liquid and vapour flows. This type of X-ray absorption dynamics is predictable and may be used for inducing particular dynamical liquid states.

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.

Chromatin-associated protein complexes play a critical role in the regulation of gene expression in health and disease. Here, the authors describe a sensitive mass spectrometry-based method to monitor the dynamic interactions of endogenous chromatin-associated protein complexes in clinical samples.

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.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Photoabsorption is a fundamental process that leads to changes in the electron density in matter. Here, the authors show a direct measurement of the distribution of electron density when a cyclohexadine molecule is excited by pulsed UV radiation and probed by a time delayed X-ray pulse generated at LCLS.

The evaporation and atmospheric oxidation of low-volatility organic vapours from mined oil sands material is shown to be responsible for a large amount of secondary organic aerosol mass—which affects air quality and climate change—observed during airborne measurements in Canada.

Genome sequencing and phylogenomic analysis show that the lungfish, not the coelacanth, is the closest living relative of tetrapods, that coelacanth protein-coding genes are more slowly evolving than those of tetrapods and lungfish, and that the genes and regulatory elements that underwent changes during the vertebrate transition to land reflect adaptation to a new environment.

Crystal structures of BAK core domain dimers suggest a mechanism by which lipids contribute to the oligomerization of BAK, which is essential for BAK-mediated permeabilization of the mitochondrial outer membrane.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.

Quantum coherence and dephasing in molecular motions determine the behaviour of many chemical reactions and are the fundamental basis for the concept of coherent control. Now, ultrafast X-ray scattering combined with a detailed structural determination analysis precisely measures the coherent vibrational motions of a polyatomic organic molecule following photoexcitation.

Functional interplay of sex hormones in estrogen receptor–positive breast cancer unveils the therapeutic potential of androgen receptor agonists.

Advanced paternal age associates with increased risk for psychiatric and developmental disorders in offspring. Here, Taylor et al. utilize parent-child trio exome sequencing data sets to estimate the contribution of paternal age-related de novo mutations to multiple disorders, including heart disease and schizophrenia.

Stabilization of DNA quadruplex structures (G4) is lethal for cells with a compromised DNA repair pathway. Here, the authors show that CX-5461, a small molecule in clinical trials as RNA polymerase inhibitor, has G4-stablization properties and can be repurposed to target DNA repair-defective cancers cells.

PTEN copy number loss is found in 25% of fusion-negative rhabdomyosarcomas (FN-RMS). Here, the authors use a Hedgehog-driven FN-RMS mouse model to show that PTEN loss drives the expression of core transcription factor PAX7 and its transcriptional axis, which determines FN-RMS tumour identity.

Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis.

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.

Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

Fernando Pardo-Manuel de Villena and colleagues generate a 3 × 3 diallel cross of three inbred mouse lines and examine gene expression in multiple tissues. They identify allelic imbalance favoring the expression of the paternal allele across the genome.

For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

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.

Iceberg-trajectory models along with multi-proxy evidence from sediment cores from the Indian Ocean show that northward shifts in Antarctic iceberg melt redistributed freshwater in the Southern Ocean during the Pleistocene.

SMARCA4 loss in non-small-cell lung cancer creates a metabolic dependency on oxidative phosphorylation that can be targeted using a new small-molecule inhibitor.

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