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This trial found spinal cord stimulation was well tolerated in people with gait-impaired Parkinson’s disease. It suggests that longer use improved lower-body motor symptoms while reducing thalamic hypermetabolism and cholinergic overactivity.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

The SONAR trial showed that the endothelin receptor antagonist atrasentan improves kidney outcomes in patients with type 2 diabetes and chronic kidney disease, though individual responses varied. Here the authors report exploratory analyses of the SONAR trial that identify urinary clusterin as a potential predictor of kidney disease progression and response atrasentan in type 2 diabetes.

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.

A measurement strategy is described that is able to read out the parity of minimal two-site Kitaev chains in real time, by coupling two Majoranas and resolving their quantum capacitance.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

CDK4/6 inhibitors are promising treatments for ER+ breast cancer, however resistance remains a challenge. Here, the authors analyse the NeoPalANA cohort and indicate that a 33 gene signature was predictive of response to neoadjuvant anastrozole and palbociclib.

The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Deeper proteome coverage empowers new biological insights. Here, the authors establish a standard analysis workflow for TMT-based data acquired on the Orbitrap Astral mass spectrometer and leverage it for aging research, distinguishing protein dynamics of early development and adulthood in mice.

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.

Microbial carbon use efficiency is a strong predictor of soil organic carbon stocks. Here the authors reveal that the microbial growth rate is a more reliable and informative predictor, and that modelling approaches tend to overemphasize the role of biotic over abiotic controls compared to empirical data.

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

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.

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.

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.

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.

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.

The success of allogeneic hematopoietic stem cell transplantation for the treatment of haematological cancers is limited by the morbidity and mortality associated with graft-versus-host disease (GVHD). Here the authors show that the microbial metabolite desaminotyrosine contributes to graft-versus-leukemia responses while protecting against GVHD and promoting mTORC1 and STING-dependent intestinal regeneration.

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.

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 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.

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.

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.

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.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

The authors show that bichromatic moiré superlattices formed by two mismatched moiré patterns in van der Waals semiconductor heterotrilayers stabilize quadrupolar moiré trions and enable electric-field tuning of excitonic and electronic ground states.

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.

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.

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.

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.

This study reveals that mobile transcriptional regulators DELLA and SHORT-ROOT control the number of root inner cortex cell layers able to host symbiotic arbuscular mycorrhizal fungi in Medicago truncatula.

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.

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.

Water splitting using earth-abundant materials promises a low cost solution to the problem of large scale energy storage. Here, the authors fabricate a haematite and silicon-based high-efficiency water splitting device, which operates without the need for an externally applied bias.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

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.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

“Dissolved oxygen (DO) sustains river ecosystems, but the effects of hydrological extremes remain poorly understood. Here it is shown that sudden floods cause abrupt declines in DO, suggesting that increased future flooding may lead to the degradation of aquatic ecosystems.

Genome-wide association meta-analyses of attention-deficit/hyperactivity disorder symptom measures and clinical diagnoses identify new risk loci, highlight putative effector genes and yield improved polygenic risk scores.

Light-matter interactions with single quantum emitters are generally difficult to measure with both high-resolution and a large field of view. Here, Johlin et al. develop far-field super-resolution fluorescence methods to map near-field emitter-nanostructure interactions over several microns.

Ying, Paulson and collagues have developed an open-source framework, Biolearn, to harmonize and systematically evaluate 39 aging biomarkers across diverse populations, enabling standardized validation and facilitating development of robust aging biomarkers.

Understanding the ground state (GS) phase transitions in the quantum tunneling regime of a superconducting system is important for future qubit devices. Here, Shen, Heedt and Borsoi et al. report distinct types of fermion parity GS transitions as a function of magnetic field and gate voltages in a Coulomb-blockaded InSb–Al island.

The authors provide a comprehensive characterization of how glutamine uptake and utilization regulate macrophage function in atherosclerosis.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.