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Suet Yi Leung, Mao Mao and colleagues report whole-genome sequencing of 100 gastric cancers and DNA copy number, gene expression and methylation profiling of these tumors. They identify new recurrently mutated genes and find mutation of RHOA in 14% of diffuse-type gastric cancers.

The authors seek to understand the precise roles of microglia in the early human brain by coculturing brain organoids with primitive-like macrophages generated from the same human induced pluripotent stem cells (iMac).

A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and potency.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

Rydberg atom arrays are a promising platform for simulating many-body systems. The authors introduce a tensor-network method to compute phase diagrams of infinite arrays with long-range interactions and experimental-scale finite arrays, unveiling a new entangled phase and offering a guide for experiments.

Cancer cells can affect cancer progression by producing systemic effects. Here, the authors show that IGF2 produced by oesophageal cancer cells increases secretion of VEGF from cancer-associated fibroblasts resulting in systemic mobilization of bone marrow-derived cells and increased metastases.

The role of soluble angiotensin converting enzyme 2 (sACE2) in SARS-CoV-2 infection is not well understood. Here, authors show that membrane type 1 matrix metalloproteinase (MT1-MMP) releases sACE2 to promote SARS-CoV-2 cell entry in vitro and in vivo, and the upregulation of MT1-MMP may contribute to increased susceptibility to SARS-CoV-2 infection in ageing.

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

A method to compute the quantum harmonic free energy contributions in large materials and biomolecular simulations at a reasonable cost is proposed, making quantum mechanical estimates of thermodynamic quantities possible for complex systems.

Wide-spread outbreaks of pathogens require high intensity testing to manage. Here, the authors present C19-SPAR-Seq, a scalable and automated platform to analyse tens of thousands of SARS-CoV-2 patient samples in a single run.

The systematic characterization of C. elegans morphology during development has yet to be performed. Here, the authors produce a 3D atlas of C. elegans morphology from 17 embryos and 54 developmental stages, using an automated pipeline, CShaper (combining segmentation of fluorescently labeled membranes with automated cell lineage tracing).

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.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

The extent of problems in quantum chemistry for which quantum algorithms could provide a speedup is still unclear, as well as the kind of speedup one should expect. Here, the authors look at the problem of ground state energy estimation, and gather theoretical and numerical evidence for the fact that an exponential quantum advantage is unlikely for generic problems of interest.

Many-electron quantum modelling of the metal clusters in metalloenzymes is a long-standing ambition for theoreticians. Here, using the density matrix renormalization group, the many-electron wavefunctions of the Mn₄CaO₅ cluster of photosystem II are computed, providing new insights into the electronic structure and reactivity at the level of many-particle quantum mechanics and entanglement.

Patients with cystic fibrosis harbour mutations in the CFTR chloride channel and often develop diabetes for reasons that are poorly understood. Here Guo et al.show that CFTR is involved in the regulation of glucose-stimulated insulin secretion from pancreatic β-cells.

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.

Ching-Lung Cheung and colleagues report a genome-wide association study for thyrotoxic periodic paralysis (TPP), a life-threatening complication of thyrotoxicosis, in a Chinese population. They identify associated variants at 17q24.3 near KCNJ2.

Nasopharyngeal carcinoma (NPC) is a malignant cancer type with high morbidity in Asia, and its current molecular classification is insufficient to predict therapy outcomes. Here the authors explore NPC subtype-specific response to therapy with a pharmacogenomics strategy integrating genomics and drug response of patient-derived organoids.

This Registered Report presents the results of the Long-read RNA-Seq Genome Annotation Assessment Project, which is a community effort for benchmarking long-read methods for transcriptome analyses, including transcript isoform detection, quantification and de novo transcript detection.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

The electronic structures of the metal cofactors of nitrogenase are key to biological nitrogen fixation; however, the [Fe₈S₇] P-cluster and FeMo cofactor have eluded detailed electronic characterization. Now, the electronic structure of the P-cluster of nitrogenase has been revealed at the many-electron level through exhaustive quantum wavefunction simulations.

This study shows that immune-related genes are primed for transcription by proximal lncRNAs. One such lncRNA, UMLILO, directs the WDR5–MLL1 complex to CXCL chemokine promoters, facilitating H3K4me3 deposition.

A PROTAC termed P4B targeting BRAF V600E mutant has been developed, which displays enhanced inhibitory function in cell lines carrying BRAF mutations that impart resistance to conventional BRAF inhibitors.

The quantum imaginary time evolution and Lanczos algorithms offer a resource-efficient way to compute ground or excited states of target Hamiltonians on quantum computers. This offers promise for quantum simulation on near-term noisy devices.

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.

Chia-Lin Wei, Yijun Ruan and colleagues used chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) to determine the CTCF-chromatin interactome in mouse embryonic stem cells.

Nonsense-mediated decay is a surveillance pathway that removes transcripts containing a premature stop codon. UPF3 is unusual among the trans-acting factors in the pathway because there are two distinct homologs, UPF3A and UPF3B. Given that patients with reduced UPF3B contain upregulated levels of UPF3A, a regulatory interplay between the two factors is uncovered, where competition for UPF2 binding destabilizes the unbound factor.

The assembly of the durian genome provides insights into the unique flavor profile of this tropical fruit. Transcriptome and metabolome analyses show that methionine γ-lyase is upregulated and that volatile sulfur compounds are produced during ripening.

FeS clusters are a universal motif in organisms and are central to many processes, including nitrogen fixation and respiration. By carrying out the first many-electron calculation of the [2Fe-2S] and [4Fe-4S] clusters, they are shown to have an unusual set of closely packed energy levels, which are key to understanding their reactivity.