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Whole-genome sequencing of polioviruses in Uganda following nOPV2 use showed high genetic stability and no sustained transmission, even though a rare double recombinant strain regained virulence, but did not spread due to high vaccination coverage.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Here the authors perform longitudinal sampling of lymphoid organs along with fate mapping and matched single-cell RNA sequencing and TCR sequencing to define the developmental dynamics of follicular regulatory T (T_FR) cells. They find that T_FR cells undergo clonal expansion and progressive differentiation in a process that requires follicular helper T cells.

Comparative genomics and high-resolution mass spectrometry reveal the biosynthetic gene clusters, and vast chemical diversity of natural products that they encode, in Photorhabdus and Xenorhabdus, bacteria that interact with hosts as symbionts and entomopathogens.

Homologous recombination rearranges genetic information during meiosis to generate new combinations in the genome. Here, the authors report direct, single-individual detection of recombination in primates and humans using long-read sequencing.

The interplay between the chromatin landscape and plant domestication remains unclear. Here, the authors report the genome assembly and chromatin landscape map of amaranth and reveal the association between domestication and species-specific changes in chromatin accessibility, with a bias toward opening chromatin regions.

A pangenome of oat, assembled from 33 wild and domesticated oat lines, sheds light on the evolution and genetic diversity of this cereal crop and will aid genomics-assisted breeding to improve productivity and sustainability.

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.

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.

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

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

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.

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.

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.

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 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.

mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.

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 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.

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.

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.

Somatic mutations have been reported in pancreatic adenocarcinomas. Here, Sausen et al. identify further mutations and find that mutations in the chromatin modifying gene, MLL, are associated with increased survival, and that the presence of circulating tumour DNA in the serum of patients is associated with poor survival.

Exhausted T cells arise when chronic activation triggers functional defects. Here the authors show that chronic antigenic stimulation in both tumour and infection models induces the expression of EGR2, which drives and stabilises exhausted cell epigenetic and transcriptional identity.

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.

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.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Non-genetic malignant clonal dominance is a cell-intrinsic and heritable property that underpins clonal output and response to therapy in cancer. 

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

BCL6 corepressor (BCOR) is recurrently mutated in acute myeloid leukaemia and myelodysplastic syndrome. Here, the authors use mouse models to show the mechanism of how inactivation of BCOR in haematopoietic stem cells contributes to the development of leukaemia.

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.

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.

Molecular alterations in ctDNA of patients with mantle cell lymphoma uncovers mutations in SWI–SNF associated with resistance to ibrutinib and venetoclax combination and provide a rationale for restoring sensitivity through Bcl-xL inhibition.

Analysis of more than 95% of each diploid human genome of a four-generation, twenty-eight-member family using five complementary short-read and long-read sequencing technologies provides a truth set to understand the most fundamental processes underlying human genetic variation.

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.

In this work, authors utilise genome-wide CRISPRi screening to identify vulnerabilities in isoniazid-resistant strains of Mycobacterium tuberculosis.

The origin and nature of rebound HIV-1 virus following antiretroviral therapy (ART) discontinuation still remains unclear. Here, Liu et al. suggest that intact proviral DNA in peripheral blood and lymph node mononuclear cells during ART suppression likely is the source of viral rebound following ART discontinuation.

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.

Follicular helper T cells play critical roles in the formation of high affinity antibody responses, but the signals involved in the development of these cells after initial differentiation are poorly understood. Here Podestà, Cavazzoni and colleagues characterise transitionary phases of follicular helper T cell development and how progression through these stages is linked to humoral immunity.

Mutations provide the genetic variability required for evolutionary change. Here, using pedigree-based whole genome sequencing, the authors determine that the Epaulette shark appears to have the lowest mutation rate identified in a vertebrate, providing a potential explanation for slow evolution in the shark lineage.