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The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

Defective ribonucleotide excision repair causes ID4, an indel cancer signature characterized by deletions of 2–5 base pairs.

Blocking T cell activation in organ transplantation is important to prevent rejection. Here the authors show that unconventional monocyte-derived host dendritic cells enter allogeneic grafts to amplify the T cell response outside lymph nodes.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Using kidneys from a genetically engineered porcine donor transplanted into a cynomolgus monkey model, the design, creation and long-term function of kidney grafts supporting life are explored.

Analysis of northern elephant seal populations shows no evidence of inbreeding depression, probably because a recent extreme bottleneck purged much of the genetic load.

The viral delivery of a miniaturized form of a master protein that establishes dyads (nanostructures involved in excitation–contraction coupling in cardiomyocytes) improved dyad architecture and normalized cardiac function under pressure overload.

It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

Renal cell carcinoma (RCC) is a common and aggressive malignancy. Here, the authors generate two mouse models of the most common RCC subtypes: the human papillary RCC throughMYC activation and clear cell RCC through MYC activation combined with Vhl and Cdkn2adeletion.

Interactions between plexin B2 on hepatocytes and sempahorins on disseminated tumour cells regulate metastatic seeding in the liver.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

A study uses single-molecule footprinting to measure protein occupancy at regulatory elements on individual molecules in human cells and describes how different properties of transcription factor binding contribute to gene expression.

Whereas large planets, such as gas giants, are more likely to form around high-metallicity stars, terrestrial-sized planets are found to form around stars with a wide range of metallicities, indicating that they may be widespread in the disk of the Galaxy.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

In this Review, Smith et al. summarize the most recent findings on AMPK and emphasize its role as a nutrient sensor and in regulating metabolic homeostasis, as well as how AMPK dysregulation contributes to various diseases.

Reference assemblies of great ape sex chromosomes show that Y chromosomes are more variable in size and sequence than X chromosomes and provide a resource for studies on human evolution and conservation genetics of non-human apes.

Broken chromosomes are lethal to cells with breaks ends often containing complex DNA damage. Here, the authors reveal a key role for the SNM1A enzyme in cleaning up break ends. Key anticancer drugs, and therapeutic radiation produce complex DNA breaks, making SNM1A an appealing therapeutic target.

Evolutionary distinctness is used as a metric to determine conservation priorities across all Chondrichthyes, identifying 21 countries with the highest richness, endemism and evolutionary distinctness of threatened species as targets.

Sequencing of over 600 genes in a large collection of lung adenocarcinoma samples provides an overview of somatic mutations and signalling pathways altered in cancer genes in this tumour type.

We present the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference.

During tuberculosis infection there is formation of a TB containing lesion within the lungs. Here the authors characterise the cellular and molecular features of human TB lesions and demonstrate associations with clinical severity and treatment efficacy.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

A comprehensive analysis of the cell-specific molecular regulatory mechanisms underlying post-traumatic stress disorder in the human prefrontal cortex.

An exploration of previously undescribed variants from the long tail of the CRISPR–Cas distribution.

Pancreatic cancer activates IL-6–STAT3 signalling in hepatocytes to induce the formation of a pro-metastatic niche in the liver.

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

Mutations in components of the MAP kinase pathway are associated with a group of syndromes known as RASopathies. Here, the authors identify gain-of-function mutations in BRAF in patients with RASopathies and congenital hypopituitarisms.  This article demonstrates a central role for BRAF in the development of the hypothalamo-pituitary axis leading to endocrine deficiencies in patients with RASopathies.

RMC-7977, a multi-selective RAS(ON) inhibitor, exhibits potent tumour-selective activity in multiple pre-clinical models of pancreatic ductal adenocarcinoma through a combination of pharmacology and oncogene dependence.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Theoretical models of foraging efficiency suggest that lunge-filter-feeding marine vertebrates could be as small as 10 kg. However, here the authors show with bio-logged data from filter-feeding minke whales that in practice there are minimum body-size constraints on filter feeders, below which this becomes an unviable feeding strategy.

Extrachromosomal DNA makes cancerous tumours resistant to treatment, but this research demonstrates that increasing transcription–replication conflict allows for targeted elimination of cancer cells containing extrachromosomal DNA, and thus sustained tumour regression in mice.

Genome sequence data from colorectal tumours show how adenomas progress to carcinomas on the fitness landscape.

Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1Rsignificantly associated with these traits.

Identifying therapeutic targets in rare cancers is challenging due to the lack of relevant pre-clinical models. Here, the authors generate a cancer cell line from a paediatric patient with a rare undifferentiated sarcoma and through functional genomics and chemical screens identified CDK4 and XPO1 as potential therapeutic targets in this cancer.

The microbiomes of dispersing organisms are understudied. Here, the authors examine rafting seaweed microbiomes, using oceanographic modelling to demonstrate significant community changes associated with water temperature.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

There are several pathways for CO₂ fixation in photoautotrophic and chemoautotrophic microorganisms. Here, the authors provide experimental demonstration for the operation of the reductive glycine pathway in a natural microorganism, Desulfovibrio desulfuricans.

With a comprehensive analysis of sequencing data, DNA copy number, gene expression and DNA methylation in a large number of human glioblastomas, The Cancer Genome Atlas project initiative provides a broad overview of the genes and pathways that are altered in this cancer type.

Present understanding of Plasmodium vivax biology is hampered by its inability to grow in vitro. Here, the authors developed an in vitro culture of its simian counterpart, P. cynomolgi, which shares morphological and phenotypic similarities with P. vivax, initiating a new phase in vivax research.

Comprehensive genomic and transcriptomics analyses of more than 1,300 cases of childhood T-lineage acute lymphoblastic leukaemia identify 15 distinct subtypes that are associated with specific outcomes.

Marine woodborers can digest woody biomass without the help of gut microbiota but the mechanism has remained unclear. Here, the authors provide evidence that the woodborer’s respiratory protein hemocyanin plays a central role in wood digestion and may offer a route toward biorefining of woody plant biomass.

DNA single-strand breaks in neurons accumulate at high levelsin functional enhancers.

Metabolic reprogramming is a hallmark of pancreatic ductal adenocarcinoma (PDA). Here, the authors show that in PDA cells redox and central carbon metabolism are driven by an eIF4F dependent translation program, and combined targeting of eIF4A and glutaminase can impact PDA proliferation.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.