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Schizophrenia is a complex brain disorder with its underlying protein changes generally not well understood. Here, authors show widespread alterations in the prefrontal cortex, marked by reduced energy production and disrupted synaptic function.

Nylon-11 is a common and durable polymer but possess low piezoelectric properties. Here, the authors use mechanical accelerations and strong electric fields to induce crystallization, hydrogen-bonding and dipole alignment in Nylon-11 films, achieving high piezoelectricity.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Phylodynamic modelling shows how the changing antibiotic landscape and genetic determinants of resistance shape real-world gonococcal dynamics. Experiments validated that determinants with identical resistance phenotype differed in impact on fitness.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

The mechanisms generating the head direction cell signal in rats are not fully understood. Here, two distinct types of head direction cells in the lateral mammillary and dorsal tegmental nuclei were identified: one type is angular head velocity independent, while the second type depends on the animal’s angular head velocity.

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.

Synthetic receptors are a powerful approach for engineering cell-based therapies that can sense and respond to their environment. Here cytokine receptor domains have been repurposed to develop engineered T cells that can sense and respond to cues associated with cancer or immune dysfunction.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

In this study, authors employ fragment-based lead discovery to identify WRN inhibitors. The fragment hits reveal an additional allosteric pocket and uncover a previously uncharacterized structural conformation of the WRN helicase domain with unique orientations of the ATPase domains

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.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

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.

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.

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.

Saito et al. identify sphingosine kinase 1 as a critical regulator of physiological ductus arteriosus closure and pathological supravalvular aortic stenosis through its role in smooth muscle cell proliferation and propose potential therapeutics.

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

Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

In two independent studies, Song et al. and Jiang, Dalgarno et al. present computational frameworks, perturbation-response score and Mixscale, respectively, to determine individual cellular variation in response to perturbation.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

In this work, Jeon et al. introduce the diagonal dose-response time-course (dDRTC), a fast and operationally simple mass spectrometry-based method for determining the efficiency of covalent modification (k_inact/K_I) across a wide dynamic range.

Microglial mitochondrial morphometrics and dynamics in vivo remain unclear. Here, the authors show that mitochondria are not evenly partitioned in microglia processes, nor do they follow process surveillance or acute process responses to brain damage.

The Staufen family of RNA-binding proteins are conserved microtubule dependent mRNA transporter factors. Here the authors use biochemical and functional approaches to characterize the RNA-binding properties of mouse Staufen 2 and study the mRNA binding capacity of its two domains dsRBDs 1 and 2.

CNS toxicity was unexpectedly observed for anti-miR-17 RGLS4326 in nonclinical studies. Here, authors identify AMPA receptor inhibition as the likely culprit. Replacement of 3’-terminus guanine to adenine leads to discovery of farabursen (RGLS8429) that is devoid of CNS toxicity.