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Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

After years of stigma, psychedelic compounds are edging closer to regulatory approval, with pivotal trials in tough-to-treat depression and anxiety underway.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer. Here, the authors develop a NLPHL specific model to identify 34 distinct cell states across 14 cell types that co-occur within 3 lymphocyte predominant ecotypes (LPEs) for 171 cases.

Some people who stop using topical steroids go through a withdrawal that leads to aggressive flare-ups. But not all physicians take the problem seriously.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

KDM4C regulates cathepsin L-mediated histone H3 N-terminal tail clipping through grainyhead-like 2 (GRHL2) methylation in breast cancer. This link between the cellular redox state and chromatin remodeling might represent a therapeutic target in KDM4C-amplified tumors.

Landmark trials using stem cells to treat Parkinson’s disease in the USA and Japan mark a turning point for cell therapy in neurodegeneration. Similar approaches to Alzheimer’s disease and amyotrophic lateral sclerosis are also showing early signs of promise.

Zika and chikungunya virus are co-circulating in many regions and currently there is no approved vaccine for either virus. Here, the authors engineer one vaccinia virus based vaccine for both, Zika and chikungunya, and show protection from infection and pathogenesis in mice.

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.

The application of state-of-the-art machine learning algorithms to Euclid’s first quick data release has enabled the discovery of around 500 new strong gravitational lenses, validating predictions that next-generation surveys will substantially extend the reach of strong lensing science.

Analyses of the topologically associated domains (TADs) in Marchantia polymorpha revealed a type of TCP1-rich TAD that regulates the activities of TCP1 transcription factors in modulating target gene expression.

Cancer liver metastases can be encapsulated by a fibrotic stroma. Here the authors use digital pathology to generate spatial growth pattern maps of colorectal cancer liver metastasis and show that prognosis depends on the degree of fibrotic encapsulation.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Karpinska, Zhu and colleagues characterize the structure-function relationship of the genome during cellular differentiation and demonstrate a role for enhancer-promoter interactions in gene regulation that is independent of cooperative interactions in chromatin hubs.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Mammary gland resident macrophages are known to be crucial components of the mammary stem cell niche. Here, the authors show that CXCR4⁺ macrophages form a niche that regulates the tumor-initiating activity of breast cancer cells and induces early immune evasion through the recruitment of regulatory T cells.

The nerve cord controlling the prehensile arm of the octopus has been poorly described. Here the authors explore the segmental arrangement of the nervous tissue, which guides motor control in the octopus.

Reporter gene expression history in cells is recorded with engineered fluorescent protein fibers.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

The human gut contains diverse bacterial strains that are beneficial/critical for health. Here, the authors compare the response of human gut and laboratory E. coli strains to the antibiotic tetracycline in molecular detail and find a severe dysfunction of protein synthesis only in the gut strain.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Pulmonary function is influenced by environmental factors, lifestyle, and genetics. Here, in a multiethnic GWAS meta-analysis for pulmonary function traits, the authors identify over 50 additional genetic loci, a subset of which are specific for European, African, Asian, or Hispanic/Latino ancestry.

Survival during fasting requires release of adipose tissue lipid stores and is thought to be dependent on canonical lipases, including the rate limiting action of adipose triglyceride lipase. Here the authors show that lysosomes and lysosomal acid lipase play a critical role in adipocyte lipolysis with fasting in mice.

Adaptive decision-making often requires an understanding of our agency in a situation; however, chronic stress can disrupt agency and promote inflexible, habitual behaviour by turning off a brain pathway needed for agency and activating one that promotes habit.

Most studies on HIV-1 proviruses that persist during antiretroviral therapy have focused on males with HIV-1 subtype B, even though the majority of people living with HIV globally have non-B subtypes. Here, the authors describe the proviral genetic landscape of HIV-1 subtypes A1 and D in Ugandan females and males using near-full-length proviral sequencing. The authors also describe a molecular assay for intact proviral quantification of these HIV-1 subtypes.

Knee osteoarthritis has a sex-specific phenotype with post-menopausal persons experiencing the highest incidence. Here the authors investigate the underlying mechanisms in a mouse model of menopause and find that the loss of 17β-estradiol and progesterone enhanced susceptibility to senescence, extracellular matrix disassembly and cartilage degradation.

Bioadhesive materials and patches are promising alternatives to surgical sutures and staples but many existing bioadhesives do not meet the functional requirements of current surgical procedures. Here the authors present a tissue adhesive, stretchable and rapid photo-projection compatible translational patch material which is able to deliver therapeutics.

RMC-7977, a multi-selective RAS(ON) inhibitor, exhibits potent tumour-selective activity in multiple pre-clinical models of pancreatic ductal adenocarcinoma through a combination of pharmacology and oncogene dependence.

An increase in the volume of the brain lateral ventricles is a sign of normal aging, but can also be associated with neurological and psychiatric disorders. Here, Vojinovic et al. identify seven genetic loci in a GWA study for ventricular volume in 23,500 individuals and find correlation with thalamus volume.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.