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This study found COVID-19 vaccination offers added protection against reinfection in children and adolescents with prior infection but variable effectiveness across variants. Findings support vaccination benefits beyond infection-acquired immunity.

BRCA2 mutations are well known to increase cancer risk, however, the significance of many variants remains unknown. Here, the authors combine data from two saturation genome editing studies to classify a total of 5926 variants as pathogenic or benign.

Here, the authors show that the Saccharibacteria Nanosynbacter lyticus strain TM7x elicits limited immune activation in the oral cavity, and binds to gingival epithelial cells via a T4P-dependent mechanism, leading to clustering of TLR2 receptors and subsequent caveolin-mediated endocytosis.

Xenotransplantation of a genetically edited pig kidney with a thymic autograft into a brain-dead human for 61 days with immunosuppression resulted in stable kidney function without proteinuria, and xenograft rejection was treated and reversed by the end of the study.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

In a short-term study in which hearts from gene-edited pigs were transplanted into two recently deceased human recipients, the hearts were able to function for the duration of the study without signs of rejection and without evidence of pig virus transmission, encouraging further clinical study of cardiac xenotransplantation.

Barcia Durán, Dayasagar, et al. map the expression of immune checkpoints in human atherosclerosis and examine the influence of lipid-lowering treatments and type 2 diabetes to understand how immune checkpoint inhibitors worsen cardiovascular risk in survivors of cancer.

SGLT2 inhibitors lower blood glucose in patients with diabetes. Here, the authors report that fasting reduces renal expression of Sglt2 and glucose reabsorption by modulating circadian clock genes.

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.

Elevated triglyceride-rich lipoproteins (TRLs), long linked to cardiovascular disease, were thought to be harmful mainly in their remnant form. Here, the authors show that intact TRLs, not just their remnants, promote atherosclerosis and vascular inflammation in a mouse model.

Asymptomatic antimicrobial-resistant infections can contribute to transmission in hospitals but are often undetected. Here, the authors develop a computational framework using patient mobility data, electronic health records, clinical cultures, and genome sequencing to estimate patient colonisation risk.

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

A Fab-IL-10 fusion protein that binds to LDL suppresses vascular inflammation in atherosclerotic mouse models.

DREDge is a software tool for motion correction of high-density electrophysiology recordings. It can handle action potential or local field potential data and is demonstrated on a variety of acute or chronic recordings from humans, nonhuman primates and mice.

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.

Long COVID has heterogeneous presentation and clinical trajectories are not well defined. Here, the authors define trajectories using data from a prospective cohort study in the United States involving symptom questionnaires from acute infection up to 15 months.

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.

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.

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 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.

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.

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.

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.

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.

Multi-omics profiling of the blood and heart of two human decedents receiving pig heart xenografts, including single-cell studies, reveals early immune responses and perioperative cardiac xenograft dysfunction in one of the two decedents, which may be due to mismatched heart size and/or insufficient immunosuppression.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Here, Rueff et al engineered a CRISPRi-based oscillator to rewire capsule production in Streptococcus pneumoniae from its native control. They show that heterogeneity in capsule production is beneficial for fitness in several virulence associated traits.

Cortical networks switch from asynchronous firing to sudden synchronized population events. Here, the authors show that differential excitatory short-term synaptic plasticity onto either excitatory or inhibitory targets establishes and shapes the dynamics of these population events.

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.

Ultrathin-film nanoporous membranes promise low-cost and high-performance separation for applications such as water desalination and the purification of natural gas. Here, the authors adopt a molecular dynamics approach to assess the potential of reduced grapheme oxide as such a material.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.