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Benjamin Raphael and colleagues report an analysis of altered subnetworks of somatic aberrations in TCGA pan-cancer data sets, including 3,281 samples from 12 cancer types, using a newly developed HotNet2 algorithm. They identify 16 significantly mutated subnetworks and provide a more comprehensive view into altered pathways, including those with known roles in cancer development.

In June 2022, the IXPE satellite observed a shock passing through the jet of active galaxy Markarian 421. The rotation of the X-ray-polarized radiation over a 5-day period revealed that the jet contains a helical magnetic field.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.

Although structural variation has been previously associated with autism spectrum disorders, this study reports a genome-wide significant association of common variants with susceptibility to this disorder group. The results implicate neuronal cell-adhesion molecules in the pathogenesis of this group of neurodevelopmental and neuropsychiatric disorders.

Mantle cell lymphoma can be refractory to treatment. Here, the authors used single cell sequencing to study the tumours of patients that were responsive and resistant to treatment and find gains of 17q in resistant tumours, which they attribute to increased expression of Birc5 and validate these findings in mouse models of the disease.

It remains poorly understood how the onset of Alzheimer’s disease affects spatial cognition. Here, the authors report that spatial coding in grid cells deteriorates over time in a mouse model of Alzheimer’s disease during the early stages of pathology while place cell and head direction coding remain intact.

Understanding the tumor microenviroment is important before it can be exploited therapeutically. Here, the authors use single cell sequencing to study stromal cells in mouse tumors and identify a subset of interferon-licensed cancer associated fibroblasts that appear after anti-TGFβ treatment.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

The autism spectrum disorders are complex genetic traits characterized by various neurodevelopmental deficits. Here, the authors analyse defective gene family interaction networks in autism cases and healthy controls and identify potential gene family interactions that may contribute to autism aetiology.

The analysis of multiple SIV vaccine regimens in macaques leads to the identification of a key two-amino-acid signature that confers resistance to neutralizing antibodies; a similar mechanism of immune escape is shown to operate in HIV and may explain the limited efficacy seen in HIV vaccine trials.

Thymocytes must undergo positive selection to survive and emigrate to the periphery as mature T cells. Glimcher and colleagues identify CHMP5 as a TCR-sensitive regulator of positive selection that acts by preventing oxidation and degradation of the pro-survival protein Bcl-2.

Nancy Bonini and colleagues performed a genome-wide yeast screen for modifiers of TDP-43 toxicity and identified genes in RNA metabolism, including several RNA-binding proteins with connections to stress granules. They determined that therapeutic modulation of stress granule–associated eIF2α phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models in flies and primary mammalian neurons.

Network propagation is based on the principle that genes underlying similar phenotypes are more likely to interact with each other. It is proving to be a powerful approach for extracting biological information from molecular networks that is relevant to human disease.

Reciprocal connectivity enables tightly coupled information processing across cortical areas. Here the authors develop a visual oculomotor task in mice, identify a small motor area required for it, and demonstrate selective exchange of sensory and motor information between the motor and sensory areas.

Joana Carlevaro-Fita, Andrés Lanzós et al. present the Cancer LncRNA Census (CLC), a manually curated dataset of 122 long noncoding RNAs (lncRNAs) with experimentally-validated functions in cancer based on data from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. CLC lncRNAs have unique gene features, and a number display evidence for cancer-driving functions that are conserved from humans to mice.

Establishing the relative transmissibility of emerging variants of SARS-CoV-2 is key for pandemic management. Here, the authors use full-population administrative data from Denmark linked to PCR test results and estimate that the Alpha variant was ~60% higher than other strains circulating in early 2021.

The immune cells of individuals with COVID-19 show metabolic changes.

Matthew Brown and colleagues identify multiple susceptibility variants for ankylosing spondylitis through an association study based on high-density genotyping of immune-related loci. Their findings implicate numerous biological pathways in the pathogenesis of this disease and highlight shared risk factors with other autoimmune diseases.

Genomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative to systematically document links between metabolome and (meta)genome data, aiding identification of natural product biosynthetic origins and metabolite structures.

The authors report whole-blood RNA-seq for 4,871 samples from 1,570 participants in the Parkinson Progression Marker Initiative. This Resource documents blood-based transcriptomic changes associated with PD, including early increases in neutrophil gene expression with a decrease in lymphocytes.

Rectal cancer organoids retain the pathological features of matched patient tumors and recapitulate clinical responses to chemoradiation.

Genome-wide association studies are used to identify common genetic variants that affect the structure of selected subcortical regions of the human brain; their identification provides insight into the causes of variability in brain development and may help to determine mechanisms of neuropsychiatric dysfunction.

Timothy Chan and colleagues report exome and genome sequencing of 60 adenoid cystic carcinoma (ACC) tumor-normal pairs. They identify multiple pathways recurrently disrupted in ACC and provide evidence that KDM6A and PIK3CA are functionally relevant candidate ACC driver genes.

In studies in mammalian cells, polymerase theta (Polθ, also known as POLQ) is identified as the polymerase responsible for non-homologous end joining DNA repair; this DNA repair pathway acts in many tumours when homologous recombination is inactivated and the identification of the polymerase responsible may aid the development of new therapeutic approaches.

Computational analysis of antigen-specific T cell subsets highlights individual-level variation in immune response quality.