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This paper conducted a priority-setting exercise to identify ten questions that define the future direction of blue carbon science. It highlights key gaps, emerging challenges and opportunities for advancing climate mitigation, ecosystem management and evidence-based policy.

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

Dendritic cells (DCs) are required to establish thymic central tolerance. Here Srinivasan et al. use single-cell transcriptomics to define thymic conventional dendritic cell (cDC) subsets and find that CD8⁺ single-positive thymocytes modulate the thymus environment to regulate plasmacytoid DC and cDC2 homeostasis and interferon signatures in DCs, while CD4⁺ single-positive thymocytes regulate cDC1 activation via cognate and CD40L–CD40 interactions.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

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.

Robbins and colleagues show that cigarette smoke-induced endothelial dysfunction enables atherosclerotic plaque macrophages to drive abdominal aortic aneurysm formation in a mouse model of atherosclerosis.

Along Taiwan’s coasts, rapid sediment redistribution can drive sea-level changes with large spatial variability, leading to substantial errors in tectonic uplift estimates, according to a numerical sea-level model simulation.

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.

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.

Pucella, Maqueda-Alfaro and colleagues distinguish three developmentally related subsets of mouse plasmacytoid dendritic cells that differ in their ability to produce type I interferon and their susceptibility to virus.

CLASSIC is a high-throughput genetic profiling platform that combines long- and short-read next-generation-sequencing modalities to quantitatively assess pools of constructs of arbitrary length containing diverse genetic part compositions.

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.

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.

In a prespecified 3-year analysis of the KEN SHE trial, single-dose HPV vaccination was shown to be well tolerated and provided durable protection against cervical HPV infection in Kenyan women aged 15–20 years.

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.

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.

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.

The development of exciplex-type hosts for thermally activated delayed fluorescence organic light-emitting diodes is hindered by a lack of structural information for these donor:acceptor blends. Here, the authors report the pump-probe Step-Scan Fourier transform IR spectra for a D:A exciplex host.

Saturated N-heterocyclic pyrrolidines are common in natural products and medicinal compounds, but reconstruction of their skeletal structures to access new chemical space is a challenging. Here, the authors report a skeletal modification strategy for conversion of polar cyclic pyrrolidines into nonpolar linear dienes through a N-atom removal and deconstruction process.

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.

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.

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.

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.

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.

Ken Ong and colleagues report a genome-wide association study for age at menarche. They find LIN28B associated with age at menarche, as well as several traits related to onset of puberty in both females and males.

During organ regeneration, gene expression patterns similar to those in normal development are reestablished. Here, Kawasumi-Kita et al. explore core rebooting factors that operate during Xenopus limb regeneration. Their results indicate that hoxc12 and hoxc13 are critical for reactivating tissue growth.

Horton et al. show that early Crebbp loss in haematopoietic progenitors results in a defective p53-mediated DNA damage response, leading to the accumulation of epigenetic and genetic alterations, which promote the onset of lymphoid malignancies.

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.

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.

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.

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

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.

Ken Ong and colleagues report meta-analysis of 32 genome-wide association studies for age at menarche. They identify 30 loci newly associated with age at menarche, including four that were previously associated with BMI.

PLXDC2 marks hematopoietic stem cells in mouse and human cord blood, enabling reliable identification with reporter mice and an antibody, and serving as a tool for imaging and transplantation studies.

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.

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.

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.