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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.

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.

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 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.

Novel biochemical processes using magnetic particles have been automated to provide a robotic system to perform processes for large-scale shotgun sequencing.

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.

High-grade gliomas functionally remodel neural circuits in the human brain, promoting tumour progression and impairing cognition.

Microfluidic chain reactions encode programs structurally in situ, and can form a frugal, versatile, bona fide lab-on-a-chip with wide-ranging applications in liquid handling and point-of-care diagnostics

High-grade serous ovarian carcinoma is often associated with TP53 mutation and chromosomal instability (CIN). Here, the authors generate ex vivo cultures from biopsies and ascites of patients and perform characterization to evaluate CIN mechanisms and compare drug sensitivity with patient responses.

Skin inflammation is often accompanied by systemic disease, yet the pathways that regulate this escalation are little known. Here authors show that transgenic expression of human CD1a in mice leads to the escalation of experimental skin inflammation and systemic inflammatory disease, and the generalized symptoms could be alleviated by blocking antibodies developed against CD1a.

A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.

Epigenetic changes associated with post-natal differentiation have been characterized. Here the authors generate epigenomic and transcriptional profiles from primary human breast cells, providing insights into the transcriptional and epigenetic events that define post-natal cell differentiation in vivo.

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.

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.

In vertebrate embryos, Wnt/β-catenin signaling induces an organizer area guiding the formation of body axes and inducing extra axes upon transplantation. Here, Kraus et al. show that Wnt ligands also induce an organizer in a sea anemone, indicating that the organizer dates back over 600 million years.

Exposure of the Murchison meteorite to ultraviolet radiation is found to produce methane, suggesting a possible explanation for a substantial fraction of recently estimated Martian atmospheric methane.

Influenza A infection results in γδ T cell influx and production of IL-17 in the lungs. Here, the authors show that this effect is primed by CD1-restricted ligands that are released by infected cells and presented by B1a cells in the lungs.

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.

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.

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.

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.

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.

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.

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.

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.

“Protein relocalisation plays a major role in the innate immune response but remains incompletely characterised. Here, the authors combine temporal proteomics with LOPIT, a spatial proteomic workflow, in a fully Bayesian framework to elucidate spatiotemporal proteomic changes during the LPS-induced immune response in THP-1 cells.

HitRS is a two-component system that responds to cell envelope damage in the bacterium Bacillus anthracis. Here, the authors identify an RNA-binding protein that regulates HitRS function by modulating the stability of the hitRS mRNA. In addition, the protein binds to over 70 RNAs and affects the expression of genes involved in multiple cellular processes.

A protein platform rapidly develops peptide-focused major histocompatibility complex class I binders with high specificity.

Ultraconserved non-coding elements (UCNEs) can regulate developmental gene expression. Retinal multi-omics data integration revealed UCNEs to be candidate cis-regulatory elements during retinal development, which may be implicated in rare eye diseases.

The tumor suppressor p53 is the guardian of the genome. Here, the authors use comprehensive approaches to demonstrate that transient p53 activity induces revival stem cells to promote the regeneration of severely irradiated intestinal epithelium in mice.

Testicular aging affects male reproductive health. Here, the authors show that impaired ketogenesis in Leydig cells drives testicular aging, and boosting ketogenesis or supplementing with the ketone body BHB can help mitigate testicular aging.

Bao et al. report that a cadherin code regulates the assembly and sorting of the first three cell lineages during mammalian development and can be manipulated to enhance the efficiency of synthetic embryogenesis.

Tissues-specific gene expression requires coordinated cis-regulatory elements. Here the authors use dCas9-based enhancer targeting to remodel local epigenetic landscapes and activate or inactive transcription.

Maintaining the intestinal barrier function requires a balance of multiple signalling pathways. Here the authors show that A20, an anti-inflammatory and anti-apoptotic protein, and Atg1611, an autophagy regulator, cross-regulate their respective protein levels and function to serve compensatory and redundant roles in fine-tuning gut barrier homeostasis.

In the second case in which a genetically modified pig heart was transplanted into a living person, the xenografted heart functioned well initially, but antibody-mediated rejection occurred thereafter, pointing to the need for improved strategies to avoid this complication.

A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

The authors evaluate multiple factors to improve knock-in rates using CRISPR-mediated homology-directed repair in zebrafish, before demonstrating that prime editing is a superior alternative.