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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.

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.

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.

Lineage tracing in mice identifies a subpopulation of basal cells that express Tmprss2 and Nkx3 as the origin of ERG-driven prostate cancer. Upon expansion, these cells show an enrichment for STAT3 chromatin binding and elevated expression of KMT2A and DOT1L as dependencies for ERG oncogenicity.

Significant process has been made in using one carbon sources toward biomanufacturing. Here, the authors explore how to strength its competitiveness, and highlight latest technologies and the released patents.

The extraembryonic yolk sac is a major location for developmental hematopoiesis, but it is unclear whether non-bone marrow sources contribute during adulthood. Here they show that embryonically derived endothelial-macrophage progenitor cells located in the aorta are a bipotent source of macrophage and endothelial cells later in life.

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 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.

Ribosomal DNA is an unstable genomic region with the underlying mechanisms remaining elusive. Here the authors find that rDNA hyper recombination in Bloom Syndrome cells arises from RAD51 accumulation in the absence of long-range resection and cause genome instability through micronuclei formation.

Obtaining a high-resolution contact map using current 3D genomics technologies can be challenging with small input cell numbers. Here, the authors develop ChromaFold, a deep learning model that predicts cell-type-specific 3D contact maps from single-cell chromatin accessibility data alone.

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.

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.

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.

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

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.

piggyBat is the only known DNA transposon active in mammals. Here the authors used cellular assays and 3D structure to show that sequences within the transposon ends restrict activity, and also how transposition activity can be substantially increased.

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.

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.

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.

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.

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.

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.

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.

The V1-V2 loops of the HIV envelope protein play an important role in HIV vaccine development. Here, Rahman et al. demonstrate in macaques that the efficacy of V1-deleted envelope vaccines, abrogated by oral delivery of control nanoparticles, is rescued by nanoparticles carrying V2 scaffold peptide strengthening the mucosal V2-specific response.

The authors measure numerous ecosystem functions across an elevational gradient on Mt Kilimanjaro and find that species richness impacts function more than species turnover across sites. They also show that variation in species richness impacts ecosystem functioning more strongly at the landscape scale than at the local scale.

A rabies virus-based monosynaptic tracing method is used to show that the external globus pallidus plays a critical role in cocaine-induced behavioural plasticity.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

The slow maturation of human neurons is regulated by epigenetic modification in nascent neurons, mediated by EZH2, EHMT1, EHMT2 and DOT1L.

Here the authors show that an HIV vaccine in non-human primates that focuses antibodies on the V1V2 region of gp120 is superior to infection or immunization with whole envelope vaccines for inducing V1V2 antibodies with anti-viral functions that correlate with protection.

Zhuang et al. demonstrate that suppression of NCoR/SMRT enhances OSKM reprogramming efficiency, and that the barrier mechanism depends on the recruitment of HDAC3 to pluripotency loci by c-MYC.

There is a lack of human models to study vocal fold epithelia making it difficult to provide therapies for vocal fold disease. Here, the authors generate a human-based model of vocal fold mucosa that mimics in utero development and shows inflammation on exposure to cigarette smoke abstract.

A method called vessel isolation and nuclei extraction for sequencing (VINE-seq) produces a molecular map of vascular and perivascular cell types in the human brain and reveals their contributions to Alzheimer’s disease risk.

The contribution of central and peripheral channels of nuclear pores to transport of transmembrane proteins is unclear. Here the authors show that most inner nuclear membrane proteins use only peripheral channels, but some extend nuclear localization signals into the central channel for directed nuclear transport.

Mapping of the HIV Env surface epitopes targeted by broadly neutralizing antibodies (bNAbs) is of great interest for HIV-1 vaccine design. Here, the authors present the 3.2 Å cryo-EM structure of the bNAb M4008_N1 in complex with BG505 DS-SOSIP, an engineered native-like Env trimer and observe that the bNAb epitope is centered at the V3 crown and that M4008_N1 uses its CDR H3 to form an extended β-sheet with the β-hairpin of the V3 crown in a conformation stabilized in the prefusion trimer.

An inexpensive knotted catheter-like device made of a piezoresistive elastic silicone–liquid-metal composite performs comparably to commercial manometry devices for the sensing of gastrointestinal motility in anaesthetized pigs.

Yang et al. report that HHEX acts as a gatekeeper of pancreatic lineage specification against the liver and duodenum fates via guiding FOXA1, FOXA2 and GATA4 to activate pancreatic genes, while restraining them from activating alternative lineages.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Single-cell transcriptional profiling of primary human synovial sarcoma tumors suggests that combinatorial treatment with HDAC and CDK4/CDK6 inhibitors could enhance tumor immunogenicity.

Hematopoietic stem cells (HSCs) are essential for long-term repopulation after secondary transplantation. Here they show that SYNCRIP safeguards HSC self-renewal during regenerative stress by maintaining both proteostasis and CDC42-regulated cell polarity.

The Weyl fermions in NdAlSi mediate a helical incommensurate spin density wave, providing a rare example of Weyl-mediated collective phenomena.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Qin, Pei and colleagues report that autophagy is induced early during somatic cell reprogramming into induced pluripotent stem cells. mTORC1 and autophagy control reprogramming efficiency by modulating mitochondrial architecture and p62 levels.