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A range of humoral related adverse events can occur after treatment of haematological malignancy with chimeric antigen receptor cell therapies. Here the authors characterise the persistence of humoral immunity and response to vaccination after patients receive B cell targeted chimeric antigen receptor T cell therapy.

Genetic analyses in more than 15,000 individuals from across the Americas, including individuals with autism and family members, define the genetic landscape of autism in Latin American populations and identify significant overlap with other ancestries.

Targeted sequencing of neurodegenerative disease genes and transcriptome-wide sequencing in postmortem brain and spinal cord samples from individuals with amyotrophic lateral sclerosis or frontotemporal dementia identify somatic mutations as likely drivers of disease pathology.

A sample of X-ray-weak active galactic nuclei at high redshift may be accreting above the Eddington limit. This could explain their large masses without the need for heavy supermassive black hole seeds at cosmic dawn.

SWI/SNF complexes are mutated in 20% of cancers, yet the underlying mechanisms are poorly understood. Here, the authors identify a compensatory mechanism of chromatin regulation that becomes essential in cancers carrying mutations that broadly inactivate SWI/SNF.

Using active and passive genomic surveillance, researchers observed the rapid spread of high pathogenicity avian influenza H5N1 D1.1 viruses in wild birds during the 2024 migratory season, which coincided with detection in humans, but did not identify mammalian adaptive markers in viruses from wild birds.

Biallelic variants in RNU4-2 cause a recessive neurodevelopmental disorder that is phenotypically and molecularly distinct from dominant ReNU syndrome and associated with reduced RNU4-2 transcript levels, consistent with a loss-of-function mechanism.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Twenty years after UK Biobank was established, the incidence of dementia among participants is set to rise rapidly. In this Perspective, Matthews et al. highlight how UK Biobank has advanced dementia research in its first 20 years and consider how future developments will leverage increasing incidence to further advance understanding of dementias.

The xylosyltransferase isoenzymes XT1 and XT2 catalyze the first glycosylation step in the biosynthesis of proteoglycans. Now, bump-and-hole engineering of XT1 and XT2 enables substrate profiling and modification of proteins as designer proteoglycans to modulate cellular behavior.

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.

A distinctive population with high hunter-gatherer ancestry persisted 3,000 years later than in most European regions, contributing to later Lower Rhine–Meuse Bell Beaker users.

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.

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.

Interpreting spectroscopic data in real time remains a challenge in chemical characterization. Here a digital twin framework is developed that links first-principles theory and experimental data via a bidirectional feedback loop, enabling on-the-fly decision-making and insights into reaction mechanisms based on measured spectra during chemical experiments.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Authors demonstrate that four distinct heterodimeric complexes catalyze chondroitin sulfate chain polymerization in humans. The synthase proteins possess catalytic activity, while the polymerization factors are essential for complex formation.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

There is currently no approved influenza vaccine for newborns, so development of such a vaccine is warranted. Here the authors show, using a African green monkey newborn model, that an adjuvanted nanoparticle vaccine containing the stem region of influenza hemagglutinin can induce robust IgG responses, with the functionality of the antibodies linked to viral clearance.

Merlino et al. demonstrate that the cytokine Interleukin-27 contributes to innate antiviral immunity in the placenta and is an important defense against congenital Zika virus infection.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

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.

Plasmids can encode multiple traits that contribute to the emergence and dissemination of their bacterial hosts. Here the authors use Nanopore long-read technology to sequence the complete genomes of <2,000 bloodstream infection E. coli isolates, highlighting the contribution of chromosomal and plasmid-encoded traits in the success of different lineages.