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Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

MrVI, based on deep generative modelling, is a unified framework for integrative, exploratory and comparative analyses of large-scale (multi-sample) single-cell RNA-seq datasets.

Structural and biochemical studies of the β-barrel-assembly machinery from Flavobacterium johnsoniae reveal a subunit composition and assembly that are distinct from those of the canonical Escherichia coli complex.

Literature mining, such as systematic review and meta-analysis, is crucial for discovering, integrating, and interpreting emerging research. This study presents a specialized large language model for literature that outperforms six general LLMs and helps clinicians in study selection and data extraction tasks.

In this attempt at xenotransplantation of a lung from a genetically modified pig into a brain-dead recipient, although the grafted lung initially maintained viability and functionality, antibody-mediated rejection rapidly occurred, contributing to xenograft damage.

Polyploidy and subsequent post-polyploid diploidization (PPD) contribute to evolutionary success of plant species. Here, using 11 genomes from all nine subfamilies of Malvaceae as an example, the authors provide evidence to support the “polyploidy for survival and PPD for success” hypothesis.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Tissue-resident macrophages (TRM) are important mediators of local immunity. Here the authors show that the deficiency or inhibition of a kinase, WNK1, unlinks macrophage colony-stimulating factor signaling and resulted macropinocytosis with the downstream, potentially IRF8-mediated genetic program to bias progenitor differentiation to neutrophil instead of TRM.

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.

Dual cyclin A/B RxL inhibitors selectively kill small cell lung cancer cells and other cancer cells with high E2F activity.

Using RFdiffusion, a general method for targeting intrinsically disordered proteins and regions for protein design has been developed.

Although the number of participants is important for phenotypic prediction accuracy in brain-wide association studies using functional MRI, scanning for at least 30 min offers the greatest cost effectiveness.

A large language model designed for health monitoring provides personalized sleep and fitness predictions, insights and advice.

The authors experimentally study nonlinear light propagation with tunable dispersion, which mimics the effect of fractional derivatives. The pulses have the unique features that their spectra have a discontinuous derivative and they decay slowly in time.

In this work, authors convert fallen leaves into energy harvesters using hygroscopic iron hydrogel, achieving continuous power generation from moisture. The device delivers high current density and power output with potential for lower environmental impact compared to alternative harvesters.

Autism genes converge in midfetal cortical co-expression networks, and chromatin regulators such as CHD8 are increasingly associated with autism spectrum disorder (ASD). Here the authors map CHD8 targets in developing brain, and find that CHD8 directly regulates other ASD risk genes during human neurodevelopment.

A graph neural network framework enables individualized genetic risk prediction at the single-cell level.

Synthetic routes to aminoglycosides are often long and rely upon the coupling of semisynthetically produced fragments. Now, an enantioselective, copper-catalysed hydroamination of benzene has been developed to enable access to the aminoglycoside antibiotic ribostamycin. This bottom-up strategy provides modular and expedient entry into the aminocyclitol class.

Hosseinzadeh et al. demonstrate use of a publicly accessible automated machine learning platform to differentiate between a common benign tumor and malignant transformation of it within the paranasal sinuses. This AI algorithm beat prior human prediction, and showed that physicians with no coding background can effectively utilize this tool.

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.

A single-cell sequencing study using more than 30,000 tumour genomes from human ovarian cancers shows that whole-genome doubling is an ongoing mutational process that drives tumour evolution and disrupts immunity.

Spin waves are excited in a thin film of bismuth-doped yttrium iron garnet using radio-frequency pulses and interact with magnetic domain walls. Pulses as short as 1 ns translate a domain wall over 15 µm distances, offering control over domain-wall dynamics.

Cytidine triphosphate synthase, a key enzyme in nucleotide synthesis, forms distinct filaments in Mycobacterium tuberculosis that resist cytidine triphosphate feedback inhibition, which are characterised through structural, biochemical, and cellular methods.

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.

Protein citrullination regulates the physiological function of proteins and is linked to various autoimmune disorders. Here, the authors report on the allosteric targeting of PAD1-4 leading to broad inhibition of protein citrullination in neutrophils.

A study generates a clinicogenomics dataset resource, MSK-CHORD, that combines natural language processing-derived clinical annotations with patient medical data from various sources to improve models of cancer outcome.

The Mass Spectrometry Query Language (MassQL) is an open-source language that enables instrument-independent searching across mass spectrometry data for complex patterns of interest via concise and expressive queries without the need for programming skills.

O’Shea and colleagues examine the three-dimensional chromatin architecture of the type 2 cytokine locus and how it differs between innate ILC2 cells and adaptive T_H2 lymphocytes.

Exposure of mice to high fructose during gestation or early postnatal life causes decreased microglial phagocytosis during brain development and leads to anxiety-like behaviour in adolescence.

The weakest interactions of protein complexes are thought to be lost when such assemblies are removed from their natural, watery environments. Not so, reveals a study in the vacuum chamber of a mass spectrometer.

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.

Combined high-throughput protein engineering with machine learning to curate libraries of CRISPR genome-editing enzymes with distinct genome targeting properties is described.

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.

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.

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.

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.

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.

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.

Clinically significant genetic variation in Asian populations is under-characterized. Here, the authors show the diversity in prevalence and spectrum of human disease and pharmacogenetic variants in a multi-ethnic Asian population.

A modular anti-albumin nanobody conjugated to a STING agonist enhances antitumour immunity by improving pharmacokinetics, tumour accumulation and immune responses, inhibiting murine tumour growth and enhancing cancer immunotherapies.

Cryo-electron tomography requires thin samples. Few cell-thinning techniques have been standardized. Here, the authors provide and validate a method to prepare, label, and image proteins at mammalian cell plasma membranes for sub-nanometer structural analysis.