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Neural crest cells have been implicated in heart development, yet the mechanisms by which they act have remained elusive. Here, the authors show neural crest cells modulate Wnt signalling in cardiac progenitors, providing new insight into the mechanisms underpinning congenital heart defects.

The omentum is the main metastatic site for ovarian cancer. Here, the authors present a human cell atlas of both benign and omentum metastatic ovarian cancer, providing insights into established metastatic sites but also of the omentum pre-metastatic niche.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.

Time-dependent calculations are widely employed in simulating spectra. Here, the authors present a basis set truncation scheme to analyse and accelerate TDDFT calculations with negligible change in the resulting electronic spectra.

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.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Intratumoral tertiary lymphoid structure (TLS) density has been associated with better prognosis in several cancer types. Here the authors provide a comprehensive characterization of TLSs in patients with high-grade serous ovarian carcinoma.

HistoPlexer, a deep learning model, generates multiplexed protein expression maps from H&E images, capturing tumour–immune cell interactions. It outperforms baselines, enhances immune subtyping and survival prediction and offers a cost-effective tool for precision oncology.

In the Tumor Profiler proof-of-concept observational study, a multiomics approach for profiling tumors from patients with melanoma was feasible, returning data within 4 weeks and informing treatment recommendations in 75% of cases.

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.

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.

How the histone variant H2A.Z controls cell fate remains unclear. Here, the authors reveal that the H2A.Z interacting partner HMG20A plays a key role in regulating transcription during early head and heart development.

Genome-wide association analyses of two oral glucose tolerance test-derived measures of postprandial insulin resistance discover ten new loci. Functional characterization identifies nine candidate genes implicated in the regulation of GLUT4.

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.

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.

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.

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.

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.

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.

Multiple types of DNA damage can lead to mutations in normal cells, ultimately contributing to the development of cancer. Here, the authors redefine the spectrum of mutational signatures linked to a particular type of DNA damage to uncover the protective role of specialized DNA repair mechanisms.

Long-read single-cell RNA sequencing is capable of detecting isoform-level gene expression and genomic alterations such as mutations and gene fusions, thereby providing cell-specific genotype-phenotype information. Here, the authors use long-read scRNA-seq on metastatic ovarian cancer samples and detect cell-type specific isoforms and gene fusions that may otherwise be misclassified in short-read data.

Myeloid and lymphoid cells are derived from the same multipotent progenitor cell. Camargo and colleagues show that the transcription factor Mef2c restricts myeloid differentiation to favor production of B, T and natural killer cells.

The T cell response to SARS-CoV-2 is detected by a PCR assay on whole blood.

The extensive information capacity of DNA makes it an attractive alternative to traditional data storage. DNA-Aeon is a DNA data storage solution that can correct all error types commonly observed in DNA storage, while encoding data into sequences that meet user-defined constraints such as GC content, homopolymer length, and no undesired motifs.

The cryo-electron microscopy structure of the filamentous hydrogen-dependent CO₂ reductase (HDCR) enzyme from Thermoanaerobacter kivui, together with enzymatic analysis and in situ cryo-electron tomography, provides insight into the high catalytic activity of HDCR.

The role of mutations within long noncoding RNAs (lncRNAs) exons on tumour cell fitness remains to be explored. Here, the authors investigate the landscape of driver lncRNAs in primary and metastatic samples and validate the functional significance of single nucleotide variants in the NEAT1 oncogene in vitro and in vivo.

Bipolar disorder (BD) is a severe mood disorder, which has been shown to have a large genetic component. Here the authors identify two previously unreported BD risk loci and provide further insights into the biological mechanisms underlying BD development.

pH alterations are a hallmark of many pathologies including cancer and kidney disease. Here the authors describe [1,5- 13 C2]Z-OMPD as a probe for hyperpolarized 13C-MRI with good pH sensitivity and hyperpolarization properties which combined with tailored MRI protocols allow sub-minute imaging of pH, renal perfusion and filtration simultaneously.

Rengachari et al. provide a structural investigation of Pol II initiation at snRNA gene promoters and find that the snRNA-activating protein complex enables DNA opening and transcription initiation independent of TFIIE and TFIIH in vitro.

Analysis of ancient DNA from 424 individuals in the Avar period, from the sixth to the ninth century AD, reveals population movement from the steppe and the prolonged existence of a steppe nomadic descent system centred around patrilineality and female exogamy in central Europe.

He et al. develop a network-based metric of amyloid-β burden by integrating individualized brain connectomes with amyloid-PET imaging. This approach improves prediction of future cognitive decline in older adults and may support earlier identification of individuals at risk of dementia.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.