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Tpr nucleoporin is known to be essential for nuclear transport and mitosis processes. Here the authors explore the link between Tpr and genome instability providing insights into the role of Tpr in safeguarding cells from RNA-mediated replication stress.

Smc5/6, part of the structural maintenance of chromosomes (SMC) family, plays roles in genome structural integrity. Here the authors reveal that Smc5/6 acts jointly with Top3 within the STR complex to mediate DNA replication completion at genomic natural pausing sites (NPSs).

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Brain-wide recordings in mice reveal that prior expectations are distributed through recurrent loops across all levels of cortical and subcortical processing.

Nagano et al. identify the third mitotic cohesin complex, STAG3–cohesin, which, with its unique biophysical properties, weakens insulation and rewires regulatory interactions of spermatogonial stem cells, shaping the male germline nucleome.

Do proteasomes catalyze peptide splicing? Here, the authors develop and apply a method to identify spliced peptides produced from entire proteins, confirm that proteasomes produce a sizeable variety of cis-spliced peptides with well-defined characteristics, and show that non-spliced and spliced peptides are concentrated in hotspots.

Visual hallucinations are a prevalent symptom of Parkinson’s disease. Here the authors use a structural mega-analysis to show cortical regions and networks involved in visual hallucinations and associations with receptor density maps.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Lack of expression and function of chloride ion-extruding transporter KCC2 in central neurons, a consequence of various forms of neural injury, is strongly suggested to contribute to chronic pain. Here the authors identify from a screen of cancer drugs a kinase-inhibitor, kenpaullone, as an enhancer of Kcc2/KCC2 gene expression and show that it (i) alleviates pain like behaviour in animal models, (ii) repairs neural-circuit disrupting elevated chloride in pain relay neurons in the dorsal spinal cord.

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.

This study reveals that females with isolated REM sleep behavior disorder show less neurodegeneration than males. The least affected regions in females are regions that overexpress estrogen-related genes, suggesting potential sex-specific neuroprotection.

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

Horses have lived in Iberia since the Ice Age. Using ancient genomes to study their history, Lira Garrido et al. reveal a local wild lineage lasting until Late Iron Age, and highlight the far-reaching influence of Iberian bloodlines across Europe and north Africa during the Iron Age and beyond.

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.

How the immune responses induced by SARS-CoV-2 and human coronavirus (hCoV) crosstalk is still unclear. Here the authors profile the humoral responses of prepandemic and SARS-CoV-2-infected donors to find that higher hCoV antibody titers are associated with SARS-CoV-2 negativity, and with reduced hospitalization in SARS-CoV-2 positive patients.

DNA2 encodes a 5′ flap DNA endonuclease involved in replication and DNA double strand break processing. Here the authors by using a conditional degron system together with electron microscopy characterize the role played by Dna2 and Pif1 helicase during unperturbed DNA replication in S. cerevisiae.

Thermoelectric materials are required to be electrically conducting while thermally insulating, which can be challenging to achieve. Here, the authors report a thermoelectric transport regime with defect tolerant charge transport but defect intolerant heat propagation in two-dimensional coordination polymer films.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

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.

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.

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.

Epidermal cultures can treat skin diseases, such as Junctional Epidermolysis Bullosa, but the signature of stem cells is unclear. By single cell RNAseq analyses on human keratinocytes, the authors identify the molecular profile of holoclones and the role of FOXM1 in regulating the proliferative potential of epidermal stem cells.

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.

Glioma tumours are known to be heterogenous in mutation and gene expression patterns, but sampling limitations can lead to inaccurate detection of evolutionary events. Here, the authors carry out multi-omics analysis of multi-regional biopsies from 68 patients and show differential mutations in non-enhancing regions.

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.

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.

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.

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.

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.

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.

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.

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.

Age-related immune dysfunction can compromise immune responses to infection and vaccine efficacy. Across two cohorts, Dallan et al. demonstrate that protective immunity against severe acute respiratory syndrome coronavirus is optimally maintained in older adults after primary adenoviral immunization (ChAdOx1-S) and subsequent mRNA vaccine boosting (BNT162b2 or mRNA-1273).

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.

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.

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.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Histone H3-mutant gliomas are deadly brain tumours and the tumour microenvironment is not fully understood. Here the authors profile the immune microenvironment from human samples and mouse models and implicate myeloid cells in immune suppression and show inhibition of myeloid cells and checkpoint blockade demonstrates therapeutic benefits in mice.

Favaretto et al. show that the brain rapidly alternates between transient connectivity patterns, with cortical regions flexibly synchronizing with two groups of subcortical regions, and that this dynamic is abnormal in stroke patients.

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.

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.

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.

The non-structural protein NSP6 in SARS-CoV-2 has a key role in viral replication by zippering the endoplasmic reticulum membrane to establish connectors between the double-membrane vesicles of the viral replication organelle and the endoplasmic reticulum.