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Escherichia coli is widespread in healthy breastfed infants, yet its ecological role is unclear. Here, the authors provide insights into the mechanisms supporting its persistence and co-existence with dominant Bifidobacterium, including potential cross-feeding of human milk oligosaccharides.

Active wetting and fluidification of breast cancer epithelia are shown to be controlled by IRSp53 and Afadin, cell adhesion proteins that regulate multicellular viscosity and tensile state during tumour progression.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

Molecular motion at interfaces to 2D materials is governed by interfacial interactions. Here, the authors use a multimodal time-resolved photoemission approach to reveal collective molecular rotation on a 2D material following photoexcitation.

Here the authors show that transient cell cycle arrest reprograms CD8⁺ T cells into a highly energized state, increasing proliferation and antitumor activity and boosting efficacy of immunotherapies in cancer models.

Affinity-selection platforms are powerful tools in early drug discovery, but current technologies such as DNA-encoded libraries (DELs) are limited by synthesis complexity and incompatibility with nucleic acid binding targets. Here, the authors present a barcode-free self-encoded library (SEL) platform that enables direct screening of over half a million small molecules in a single experiment.

Bessler et al. developed a human organoid model for H3.3K27M-altered diffuse midline glioma that recapitulates key tumor features and demonstrated its utility for modeling CAR T cell and microglia functions.

Accessing synthetic two-dimensional polymers that are analogous to graphene is synthetically and analytically challenging. Now, single crystals of a simple-to-make monomer have been grown and then photopolymerized to form layered single crystals of covalently bonded two-dimensional polymer. Much like natural graphite, these crystals can be exfoliated to form thin sheets and single layers of the polymer.

Surprisingly consistent replication failure of gray matter correlates of childhood maltreatment raises questions about publication bias in prior literature and about prevailing models linking maltreatment to brain structure in adult populations.

Here, the authors compared measurements between 34 laboratories from 19 countries, to quantify by mass spectrometry four ceramides of clinical relevance in human blood plasma Standard Reference Materials. The main goals were to evaluate concordance obtained in a large inter-laboratory trial and to report absolute concentrations of four circulating lipids in a publicly available standard.

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.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

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.

Smeland et al. demonstrate greater genetic overlap between neurological and psychiatric disorders than previously recognized, along with diverse neurobiological associations. The findings support a more integrated view of brain-related illness.

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.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

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.

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.

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.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

SIMPLICITY models multi-scale SARS-CoV-2 evolution by integrating within-host viral dynamics and population-level transmission. Our adaptive fitness landscape model reveals how immune escape prompts evolutionary dynamics akin to the real-world evolution of SARS-CoV-2.

Kinase inhibitors are key in cancer therapy, but resistance limits their efficacy. Here, the authors develop SPIED-DIA, a phosphoproteomics method enhancing detection of key phosphorylation sites. They reveal a synergistic MEK-JNK signaling response in colorectal cancer cells, suggesting a potential therapeutic strategy.

Single crystal diffraction is one of the most common and powerful tools for structural elucidation, but obtaining single crystals of adequate size and quality is not always trivial. Here, the authors report a method to crystallize inherently non-crystalline adamantane-like organic-inorganic clusters using π-π interactions between C₆₀ and nano-sized molecules.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Here the authors investigate the regulatory mechanisms of acetyl-CoA (Ac-CoA) biosynthesis in Bacillus subtilis, probing the interaction between acetyl-CoA synthetase (AcsA) and acetyltransferase (AcuA). They capture a stable AcsA-AcuA complex that inhibits AcsA activity in the absence of Ac-CoA.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

This study presents the Cell Painting PLUS assay, a customisable phenotypic screening assay for multiplexed, iterative staining of single cells with seven fluorescent dyes for detailed mode-of-action analyses in toxicology and biomedical research.

Multiomic factor analysis of blood multiomic data, including single-cell transcriptomics, for individuals with either acute or chronic coronary syndrome identifies immune cell signatures that correlate with treatment outcomes.

Many enzymes form homo-oligomers, but it is often not clear why. This study follows the evolution self-assembly in citrate synthases across their phylogeny and finds it to be variable and not obviously related to enzyme function.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Changes to structural and functional connectivity can give rise to neurodegeneration and neurodevelopmental diseases. Here the authors investigate molecular and connectomic patterns in 13 different neurological, psychiatric and neurodevelopmental diseases from the ENIGMA consortium.

MethyLYZR, an epigenetic classifier of brain tumors, provides clinically relevant cancer classification results within 15 min of sequencing, with potential applications for neurosurgical intraoperative use.

Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Here the authors show that IL17A-producing NKp44- group 3 innate lymphoid cells accumulate in FAP duodenal tissue and are associated with duodenal adenoma formation in patients with FAP.

Lipidic sponge phase crystallization yields membrane protein microcrystals that can be injected into an X-ray free electron laser beam, yielding diffraction patterns that can be processed to recover the crystal structure.

The Arabidopsis CC1 protein maintains microtubule array stability and cellulose synthesis during salt stress. Here the authors show that CC1 engages microtubules via an intrinsically disordered N-terminus that suggests it controls microtubule dynamics in a similar way to the mammalian Tau protein.

Global riverine carbon export to the ocean may exceed previous estimates, underscoring the important role of riverine carbon to the carbon budget, according to a multi-model ensemble assessment constrained by a global dataset.

Stress is recognized as risk factor for the development of type 2 diabetes. Here Balsevich et al. show that the stress responsive co-chaperone FKBP5 regulates glucose metabolism in mice by modulating AS160 phosphorylation, glucose transporter expression and muscle glucose uptake.

In this biomarker cohort analysis of CheckMate 153, analyses of genomic alterations and neoepitope immunogenicity in tumor tissue samples from patients with non-small cell lung cancer treated with nivolumab show the evolution of neoantigens during nivolumab-induced selection pressure and how it associates with clinical response.