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Complement proteome engagement is strongly linked to kidney outcomes in diabetes. This translational study leveraged five cohorts of over 4,500 person-years and high-throughput proteomics to enable potential biomarker-guided drug development.

Picks include a quantum pioneer, a co-discoverer of Ebola and a bioethicist-turned-activist.

Birds have evolved a unique sex chromosome dosage compensation mechanism involving the male-biased microRNA (miR-2954), which is essential for male survival by regulating the expression of dosage-sensitive Z-linked genes.

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.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

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.

A comprehensive meta-analysis of global terrestrial and marine genetic diversity covering more than three decades of research demonstrates rapid loss of genetic diversity and identifies conservation interventions that could mitigate this process.

The authors show that behavior and dopamine responses track prospective, but not retrospective, contingency. These results are explained by temporal difference (TD) learning models, indicating that TD errors are a measure of contingency.

The SARS-CoV-2 Omicron lineage XBB/XBB.1.5 became the leading cause of new infections in the US in January 2023. Here, the authors use testing and hospitalisation data and show that this variant has increased ability to evade infection-derived immunity but enhanced vaccine sensitivity.

An analysis of data from 522 population-based studies encompassing 82 global regions and spanning more than a century (1920–2024) shows spatiotemporal transitions across epidemiologic stages 1 to 3 of inflammatory bowel disease, and models stage 4 progression.

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.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Continuous monitoring of SARS-CoV-2 variant properties is important for public health planning. Here, the authors use data from the United States and show that Omicron BA.4/5 subvariants, which became dominant in mid-2022, have stronger immune escape properties, but are no more severe, than the previously dominant BA.2.

Robbins and colleagues show that cigarette smoke-induced endothelial dysfunction enables atherosclerotic plaque macrophages to drive abdominal aortic aneurysm formation in a mouse model of atherosclerosis.

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.

Mice treated with a protein from umbilical cord plasma improved their performance on memory tests.

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.

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.

Whether or not marine protected areas (MPAs) deliver positive outcomes for both people and nature remains a challenging question. Using a statistical matching approach, this study provides quantitative evidence of co-benefits for fish and people associated with MPAs in the Mesoamerican region.

A chromatin accessibility atlas of 240,919 cells in the adult and developing Drosophila brain reveals 95,000 enhancers, which are integrated in cell-type specific enhancer gene regulatory networks and decoded into combinations of functional transcription factor binding sites using deep learning.

Comparison of outcomes of SARS-CoV-2 Delta and Omicron infections shows reduced severity of Omicron infections, most notably in unvaccinated individuals, and no differential risk of severe outcomes between subvariants BA.1 and BA.2. The findings highlight the importance of continual assessment of clinical outcomes associated with SARS-CoV-2 variants of concern to inform both medical interventions and healthcare resource management.

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.

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.

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.

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

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.

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.

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.

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.

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.

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 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.

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.

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.

Xie et al. combine intracranial recording, brain stimulation and lesion case study to show that the human medial temporal lobe is involved in the quality of short-term memory representation.

A synthesis of elevated carbon dioxide experiments reveals that when plant biomass is strongly stimulated by elevated carbon dioxide levels, soil carbon storage declines, and where biomass is weakly stimulated, soil carbon accumulates.

Analyses of the relationships between temperature, moisture and seven key plant functional traits across the tundra and over time show that community height increased with warming across all sites, whereas other traits lagged behind predicted rates of change.

Liver metastases reduce clinical and preclinical immune-checkpoint inhibitor efficacy through hepatic siphoning of circulating activated CD8⁺ T cells, but therapeutic benefit can be improved by combining immunotherapy with liver-directed radiotherapy.

TOI-500 hosts at least four planets, the innermost of which is an Earth-sized ultra-short-period body with a density similar to Earth. The architecture of the TOI-500 system can be explained by a slow, secular, low-eccentricity migration scenario.

A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.

A suite of methods enables programmable species- and locus-specific editing of bacteria in communities.

A pan-cancer epigenetic and transcriptomic atlas identifies epigenetic drivers associated with cancer transitions.

In an analysis of forest edge-to-interior transects in Europe, the authors show that different facets of biodiversity and different types of ecosystem service are found in forest interiors versus edges, suggesting that both have a role to play in the provisioning of ecosystem services in landscapes.

Determination of interactions between native proteins in cells is important for understanding function. Here the authors report MolBoolean as a method to detect interactions between endogenous proteins in subcellular compartments, using antibody-DNA conjugates for identification and signal amplification.

A wealth of gene expression data is publicly available, yet is little use without additional human curation. Ma’ayan and colleagues report a crowdsourcing project involving over 70 participants to annotate and analyse thousands of human disease-related gene expression datasets.

By coupling robotic cell culture systems with artificial intelligence–powered image analysis, Schiff et al. identify previously unseen characteristics of Parkinson’s disease in patient skin cells that distinguish them from healthy controls.