Search

This study develops and validates a prognostic staging framework for Alzheimer’s disease by integrating cognitive status with blood-based biomarkers, and neuroimaging data, to improve risk stratification across the disease continuum.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

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.

The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

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

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 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.

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.

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.

Kim, Park, and colleagues present near-infrared long-lifetime upconversion nanoparticles combined with time-gated detection. These nanoparticles allow for improved performance of luminescence-based biosensing for sensitive and accurate microRNA analysis in cancer diagnostics.

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.

Here the authors reveal a study of 486,956 Han Chinese individuals showing that most people with genetic variants affecting drug response do not have the predicted adverse events, highlighting the challenges of implementing pharmacogenetics in clinical practice.

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.

Ferroptosis is an iron-dependent cell death mechanism that is emerging as a target for cancer therapy. Here, the authors find that lipoprotein-associated phospholipase A2 modulates ferroptosis resistance by controlling phospholipid metabolism.

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.

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.

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.

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.

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 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.

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.

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.

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.

It is well known that the interplay between molecular ordering and interface geometry can determine the morphology of two-dimensional systems. Here, the authors report facet formation in water droplets, driven by peptide assembly, and investigate the structural and sequence motifs that affect this behaviour.

Cancer stem-like cells contribute to tumor growth and therapy resistance in glioblastoma. Here, authors identify that DHRS13 inhibition promotes differentiation of glioma stem-like cells by activating retinoic acid signaling and induces cell death through mitochondrial reactive oxygen species-driven mitophagy.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

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.

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.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Post-acute sequelae of SARS-CoV-2 (PASC) have been linked to brain alterations, but association with cognitive problems are not well understood. Here, the authors analyze blood proteins and brain MRI data one year after mild COVID-19, revealing distinct neurodegenerative processes in PASC patients with cognitive problems, such as cortical thinning, brain iron deposition, enlarged choroid plexus, and increased blood neuronal/glial injury markers, compared to other-PASC.

Tobacco smoking is an important risk factor for lung cancer. Here the authors report that tobacco carcinogens promote metabolic syndrome and metabolic reprogramming of macrophages, associated with lung cancer progression in preclinical models.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

PPARα corepressor NCoR1 is a key regulator of fatty acid β-oxidation and ketogenesis. Here, the authors demonstrate that p21-activated kinase 4 phosphorylates NCoR1 at T1619/T2124, resulting in PPARα transrepression and ketone body reduction.

Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis. Here, the authors study the roles played by 129 putative kinases in the growth and virulence of C. neoformans, identifying potential targets for development of anticryptococcal drugs.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

IgE is a critical component of the allergic response and therapeutic targeting can alleviate symptomology. Here the authors propose the combined use of Bifidobacterium longum and a FcεRIα extracellular domain linked to a IgD/IgG4 hybrid Fc domain fusion protein called IgE_TRAP and show reduction of mast cell and IgE levels in models of food allergy.

Here the authors identify silicon as an optimal element for anchoring oxygen on copper, nickel or iron surfaces to prevent oxidation. An atomically thin layer of SiMOx (M = Cu, Ni, or Fe) renders the metal surface impermeable to oxygen up to 400 °C while preserving the electrical properties.

Comparison of genome-wide association studies of HTT CAG repeat expansion in blood to expansion-driven clinical traits in Huntington’s disease identifies shared and distinct modifiers implicating DNA mismatch repair with tissue and cell-type specificity.

It is vital but challenging to develop coating technologies for addressing reliability and durability issues of electrochemical sensors when exposed to diverse and complex biological environments. Here, the authors report a micrometer-thick, porous and robust nanocomposite coating that enables highly sensitive and stable electrochemical sensors.

Eating behviours consist of seeking and consummatory phases. Here, authors show that two distinct lateral hypothalamic leptin receptor neurons orchestrate seeking and consummatory phases of eating behaviour via hunger signal, Neuropeptide Y.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

Many low modulus systems, such as sensors, circuits and radios, are in 2D formats that interface with soft human tissue in order to form health monitors or bioelectronic therapeutics. Here the authors produce 3D architectures, which bypass engineering constraints and performance limitations experienced by their 2D counterparts.