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Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

The taurine–taurine transporter axis is a critical dependency of aggressive myeloid leukaemias.

This study found higher RSV antibody levels were associated with lower RSV risk in children outside the hospital. An earlier rise in incidence and higher incidence rates were observed among children <5 years compared to older children and adults.

The authors introduce the Neurolipid Atlas, a dynamic resource for the community to gain insight into lipid alterations in neurodegenerative disease, and they leverage the platform to show how cholesterol alterations in astrocytes can dysregulate neuroinflammatory pathways in Alzheimer disease.

Embryonic stem cells for chicken and seven other avian species are derived.

Mammary gland resident macrophages are known to be crucial components of the mammary stem cell niche. Here, the authors show that CXCR4⁺ macrophages form a niche that regulates the tumor-initiating activity of breast cancer cells and induces early immune evasion through the recruitment of regulatory T cells.

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.

Hematopoietic stem cells (HSCs) differentiate into multiple lineages, with such capacity impacted by aging. Here the authors identify Kit^lo HSCs as a functionally distinct population that exhibits distinct lymphoid-primed chromatin landscapes, which drive enhanced lymphoid reconstitution capacity, and is altered in aged hosts.

PepMLM designs peptide binders against diverse targets using masked language modeling.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

This study shows how pressure induces local disorder and partial amorphization in CsPbBr₃, using total X-ray scattering and big-box modeling to reveal reversible structural changes at the atomic scale.

Acute myeloid leukaemia (AML) is maintained by self-renewing leukemic stem cells. Here the authors show that Heat Shock Transcription Factor 1 (HSF1) is specifically required for the maintenance of AML stem cells, while sparing steady-state and stressed haematopoiesis and that pharmacologically targeting HSF1 may have broad anti-leukemic effects.

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.

Jacobsen and colleagues elucidate the nonhierarchical relationship between two types of stem cells: Vwf⁻ hematopoietic stem cells that stably replenish all blood cell lineages without a platelet bias, and Vwf⁺ stem cells that replenish almost exclusively platelets, and demonstrate that the two types utilize cellularly and molecularly distinct progenitor trajectories for replenishment of platelets.

China contributed about half of the global carbon tetrachloride (CCl₄) emissions during 2011–2021, according to long-term atmospheric observations from China.

Single-cell transcriptomic and epigenetic analysis has enabled the identification of Thetis cells, a class of RORγt⁺ antigen-presenting cells with a key role in the differentiation of commensal microbiota-induced peripheral regulatory T cells.

The fibrinolytic system promotes the progression of solid tumors. Here, the authors show that the fibrinolytic agent plasmin supports B-cell acute lymphoblastic leukemia (B-ALL) progression via remodeling of the extracellular matrix, and the inhibition of plasmin activation with ε-aminocaproic acid prolongs survival in B-ALL mouse models.

HSC mutations lead to diverse clonal hematopoiesis outcomes. This study shows how epigenetic traits can predispose clones for dominance. Sox4 increases sensitivity to Tet2 KO, offering insights into variable phenotypes despite identical mutations.

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.

Ionizing radiation and chemotherapy deplete haematopoietic stem cells and damage the vascular niche. Here the authors show that irradiation induces SEMA3A secretion from bone marrow endothelial cells (ECs), inducing EC apoptosis via NRP1 and that NRP1 inhibition promotes vascular regeneration and R spondin 2 dependent hematopoietic regeneration.

The transcriptional control of lineage commitment to various ILC subsets is incompletely understood. Yokoyama and colleagues show that Runx3 is essential for the normal development of ILC1 and ILC3 cells but not ILC2 cells.

Body size and composition are complex traits that are challenging to characterize due to environmental and genetic influences. Here, Arehart et al. disentangle shared and distinct genetic signals underlying body size and composition.

GeneAgent is a language agent using large language models and self-verification to improve gene-set function annotation.

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.

Protein tyrosine phosphatase sigma (PTPσ) deficient haematopoietic stem cells (HSCs) demonstrate increased engraftment following transplantation. Here the authors identify a small molecule inhibitor of PTPσ that promotes murine and human haematopoietic stem cell regeneration via induction of the RAC pathway and BCL-X_L.

Lineage tracing analyses of cells from two monozygotic twins presenting with myelofibrosis in adulthood provide evidence of in utero transplacental transmission of the tumorigenic clone.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

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.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

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.

Kazachstania pintolopesii is a highly prevalent fungal symbiont that can trigger type 2 immunity and influence the composition of the gut mycobiome, as well as immune and disease phenotypes.

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.

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.

Restriction of dietary valine reduces growth of T cell acute lymphoblastic leukaemia through altered valine tRNA biogenesis and reduced translation of mRNAs that encode subunits of mitochondrial complex I.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Specific deletion of group 2 innate lymphoid cells in mice shows these cells have roles in the recruitment of eosinophils and in mounting immune and epithelial type 2 responses.

Roland et al. report the results of a randomized, non-comparative phase 2 trial of neoadjuvant nivolumab or a combination of nivolumab and ipilimumab in patients with resectable retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

The RNA binding protein MUSASHI-2 (MSI2) is a potential therapeutic target for acute myeloid leukemia. Here the authors identify a small molecule inhibitor of MSI2 and characterize its effects in a murine leukemia model.

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.

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.