Search

This study applies generalized linear mixed models (GLMM) and advanced transcriptome wide association study (TWAS) methods to improve the discovery of colorectal cancer risk transcription factors and genes, including potential druggable targets.

Analysing the causal links of gene expression and protein abundance on type 2 diabetes risk in blood and seven tissues related to the disease from individuals of four ancestries, the authors advance our understanding of the genetic architecture of type 2 diabetes

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

A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

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.

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.

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.

Comparative genomics of Shiga toxin-producing E. coli from healthy carriers and patients uncovers key virulence differences and supports risk-based management strategies.

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.

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.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

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.

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.

Synthetic routes to aminoglycosides are often long and rely upon the coupling of semisynthetically produced fragments. Now, an enantioselective, copper-catalysed hydroamination of benzene has been developed to enable access to the aminoglycoside antibiotic ribostamycin. This bottom-up strategy provides modular and expedient entry into the aminocyclitol class.

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

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging 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.

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.

Hydroxyl groups are among the most abundant functional groups, and thus, the development of efficient reactions for their conversion has significant importance in medicinal and process chemistry. Here, we present a redox-neutral Giese reaction via anodic oxidation to generate phosphonium ions in combination with a cathodic reduction to yield low-valent Fe-catalysts.

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.

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.

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.

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.

Here the authors report asperigimycins, fungal ribosomally synthesized and post-translationally modified peptides with a heptacyclic scaffold. After chemically modifying them for nanomolar anticancer activity, CRISPR screening identifies SLC46A3 as a key transporter for their uptake in cells.

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.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

The transcription factor CREM is a pivotal regulator of NK cell function, making CREM a valuable target to increase the efficacy of anticancer immunotherapies based on this cell population and chimeric antigen receptors.

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.

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.

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.

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.

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.

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 meta-analysis of genome-wide association study data from 77,418 individuals of East Asian ancestry with type 2 diabetes identifies novel variants associated with increased risk of type 2 diabetes.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

There are no vaccines or antivirals available against enterovirus D68. Here, the authors report Jun6504 as a 2C inhibitor and show that it provides broad-spectrum antiviral activity against EV-D68, EV-A71, and CVB3 and potent antiviral efficacy in a neonatal neurological mouse model of EV-D68 infection.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

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.