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Head motion is an artifact in structural and functional MRI signals, and some traits or groups are more strongly correlated with motion than others. Here the authors describe a method to attribute a motion impact score to specific trait-functional connectivity relationships.

The genomic profiling of tumours has not been widely adopted in the clinic due to technical and practical hurdles. Here, the authors develop PGDx elio tissue complete, a scalable, standardised and FDA-cleared test comprising a targeted gene panel and automated machine-learning analysis, which detects clinically relevant sequence biomarkers in cancer samples.

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.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Here the authors develop a probabilistic model for single-cell DNA sequencing of aneuploid tumors that infers clone-specific replication timing and S-phase fractions, unveiling their relationships with copy number evolution and clonal fitness.

Aligning electrocorticography data into a shared space improves how large language models predict brain activity during language comprehension, enhancing encoding accuracy, cross-participant generalization and denoising—especially in language-selective regions.

Bacteriophage diversity in cell-free DNA within human plasma can help to specify pathogenic Escherichia coli and Staphylococcus aureus during sepsis.

To enable a sensed RNA to activate diverse RNA effectors, the authors engineer a programmable dual-site ribozyme that, upon RNA trigger binding, self-cleaves to release an embedded RNA. It enables trigger-dependent release of diverse ncRNAs and controls CRISPR-Cas9 editing in zebrafish and human cells.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Resistance to first line treatment is a major hurdle in cancer treatment, that can be overcome with drug combinations. Here, the authors provide a large drug combination screen across cancer cell lines to benchmark crowdsourced methods and to computationally predict drug synergies.

Autoimmune encephalitis (AIE) may involve neuron-specific cytotoxic T cells, but evidence is still lacking. Here the authors use induced pluripotent stem cells from patients with AIE and single cell RNA-sequencing of ex vivo CD8 T cells to find neuron-specific, KIR⁺CD8⁺ T cells with altered transcriptome that potentially contribute to AIE etiology.

An integrative analysis of single-nucleus assay for transposase-accessible chromatin with sequencing and RNA sequencing in normal and Alzheimer’s disease brain tissue identifies cell-type-specific cis-regulatory elements and candidate target genes at disease-associated loci.

In single-cell RNA-seq analyses, it would be critical to measure the relationships between genes. Here, the authors develop a framework for single-cell dimensionality reduction that incorporates gene-specific relationships - GeneVector -, and use it for tasks such as annotating cell types and analysing pathway variation after treatment.

Genome-wide analyses of vaccine antibody responses in 2,499 infants from Uganda, South Africa and Burkina Faso identify associations between specific HLA genes and response to eight vaccines, providing insights that could be considered for population-adjusted vaccine design strategies.

By learning a semantics of gene function based on genomic context, the genomic language model Evo autocompletes DNA prompts to generate novel genes encoding protein and RNA molecules with defined activities, whose sequences generalize beyond those found in nature.

Carey and colleagues reveal 35 major latent constructs (factors) in the phenotype data of unrelated individuals with predominantly estimated European genetic ancestry from UK Biobank.

While greater yam provides food and income security for millions of people around the world, there are limited genomic resources available. Here, the authors report a chromosome-scale assembly of the greater yam genome as well as quantitative trait loci associated with anthracnose resistance and tuber traits.

By combining imaging and single-cell RNA sequencing, the authors identify genes regulated during cell growth and division and further analyse the heterogeneity of gene expression during adaptive and acute responses to changing environments.

Longitudinal changes in the serum metabolome and transcriptional changes in immune cells are mapped in children from two different ethnic groups in West Africa who were exposed to seasonal malaria, thereby identifying an immunosuppressive role of endogenous steroids that are induced by P. falciparum infection.

Trinucleotide-repeat-containing 18 (TNRC18), which has poorly understood functions, is now identified as an H3K9me3-specific reader that silences endogenous retroviruses.

In people with severe brain injuries, stimulation restored consciousness by engaging a deep brain circuit for wakefulness—revealing a target that may also guide treatment in stroke and epilepsy.

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.

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.

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.

Anagnostou et al. present an improved predictor of response to immune checkpoint blockade that integrates estimates of tumor mutational burden corrected for tumor purity, RTK genomic alterations, a smoking-related mutational signature and HLA status.

Pluripotent cells are defined by their ability to self-renew: to proliferate indefinitely while maintaining their identity. Here, authors use genome-scale CRISPR knockout screens to untangle these two aspects of self-renewal.

Here, the authors identify signatures of miRNA expression differentiation associated with Plasmodium falciparum infection and parasitemia in a longitudinal pediatric cohort in Burkina Faso. In particular, expression of several miRNAs known to promote lymphocyte cell death is affected during infection.

Arya et al. report that migrating neutrophils resolve acute inflammation by releasing exosomes associated with nuclear DNA. This process is distinct from the release of neutrophil extracellular traps, and relies on the lamin B receptor.

Approximately 17% of meningiomas remain genomically uncharacterized. Here, the authors analyze 105 meningiomas without known driver mutations or significant copy number alterations and identify a subgroup of meningiomas, defined by FOS/FOSB gene fusions with distinctive transcriptomic and histopathological features.

Adolescent drug use augments psychiatric risk. Here the authors show that abused drugs dysregulate adolescent Netrin-1/DCC signaling, triggering ectopic long-distance dopamine axon growth in males while Netrin1 compensatory events protect females.

The INTIMET study is a randomized 26-week double-blind clinical trial to assess whether metformin can reduce insulin resistance in adults with type 1 diabetes. Metformin did not reduce insulin resistance in type 1 diabetes, but lowered insulin dose versus placebo – a secondary outcome.

By simulating the implementation of airport-based wastewater surveillance sites at the global level, a modeling study shows how this early warning system would perform in identifying sources of pandemic outbreaks, in time and space, and what the optimal location of monitoring sites would be.

Here, using a genome-wide CRISPR screen, Bitew et al. identify GRA38, a phosphatidic acid phosphatase, as a key factor in Toxoplasma gondii adaptation to lipid-rich conditions via keeping lipid balance, sustaining growth, ultimately ensuring survival.

SWATH-mass spectrometry consists of a data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics on the scale of thousands of proteins. Here, using data generated by eleven groups worldwide, the authors show that SWATH-MS is capable of generating highly reproducible data across different laboratories.

Estimates of chikungunya virus prevalence across 180 countries and territories show that Southeast Asia, Africa and the Americas carry the most substantiative burden, which would require reactive vaccine campaigns against new outbreaks and routine immunization in heavily endemic areas to reduce transmission.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

DNA methylation from cell-free DNA (cfDNA) can be profiled using whole genome bisulfite sequencing (WGBS). Here, the authors develop a computational method, FinaleMe, that predicts DNA methylation and tissues of-origin in cfDNA and validate its performance using paired deep and shallow-coverage whole-genome sequencing (WGS) and WGBS data.

CondenSeq is an imaging-based, high-throughput platform for characterizing condensate formation within the nuclear environment, uncovering the protein sequence features that promote this process.

Plankton communities in the top 150 m of the nutrient-depleted, oligotrophic global ocean that are most associated with carbon export include unexpected taxa, such as Radiolaria, alveolate parasites, and Synechococcus and their phages, and point towards potential functional markers predicting a significant fraction of the variability in carbon export in these regions.

Typically, quantitative trait loci studies find genetic variants associated with the total quantity of a quantitative trait, but other measures, such as variance, can detect different biology. Here, the authors map variance quantitative trait loci for blood cell traits, finding associations with gene-by-environment interactions and genetically-predicted alcohol use.

The authors performed phylogenetically controlled behavioural assays and analysed brain transcriptomes across five avian families, identifying convergent patterns of gene expression associated with aggression and nesting behaviour in obligate cavity-nesting birds.

Transcriptomic and histological profiling of gut biopsies from multiple independent cohorts of patients with inflammatory bowel disease identifies distinct histopathological, molecular and cellular features associated with treatment response, providing insights for patient stratification and precision therapy.

TP63 is a master regulator transcription factor in squamous cell carcinomas (SCCs). Here the authors report that TP63 suppresses IFNγ signaling in SCC tumors and that its inhibition is associated with enhanced anti-tumor immunity and response to anti-PD1.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

The authors show that LARP4 drives T cell dysfunction in tumors by promoting hypertranslation of oxidative phosphorylation-related mRNAs, resulting in mitochondrial dysfunction. They also target LARP4 to enhance T cell persistence and anti-tumor activity and provide a CAR T cell strategy for treating solid and liquid tumors.

Murcy et al. show that increasing the plasma glutamine-to-glutamate ratio in atherosclerosis can distally reprogram transcriptional and post-transcriptional remodeling of the aorta by GLS2-dependent hepatic glutaminolysis.

Biogeographic regions reflect the organization of biotas over long evolutionary timescales. Here the authors show that climate change will lead to the persistence of some biogeographic regions and alteration of deeper biogeographic boundaries that separate historically distinctive plant assemblages.

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.