The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust.It is located on the Wellcome Genome Campus by the village of Hinxton, outside Cambridge. It shares this location with the European Bioinformatics Institute. It was established in 1992 and named after double Nobel Laureate Frederick Sanger. It was conceived as a large scale DNA sequencing centre to participate in the Human Genome Project, and went on to make the largest single contribution to the gold standard sequence of the human genome. From its inception the Institute established and has maintained a policy of data sharing, and does much of its research in collaboration.Since 2000, the Institute expanded its mission to understand "the role of genetics in health and disease". The Institute now employs around 900 people and engages in five main areas of research: Cancer, Ageing and Somatic Mutation; Cellular Genetics; Human Genetics; Parasite and Microbes; and the Tree of Life.
Aim It is well-documented that the tropical forest biota is vertically stratified, and ecological theories from studies of the latitudinal gradient have been applied to predict and understand how communities vary across vertical strata. In butterflies, differences in abiotic conditions between the canopy and the understorey promote the evolution of distinct flight morphologies and physiologies. However, how these distinct morphologies relate to differences in dispersal ability is poorly explored and we lack a general understanding of how and why vertical stratification influences community turnover in tropical forests. Here, we explored how vertical stratification influences diversity, horizontal spatial similarity of assemblages and distance-decay patterns in understory and canopy butterflies across multiple ecosystems.Location Seven forest ecosystems in Ecuador, South America.Taxon Butterflies (Lepidoptera: Papilionoidea).Methods We assessed patterns of diversity by employing data from standardized butterfly monitoring programmes during the years 2011-2019 across seven sites in Ecuador (37,370 records from 1099 species), and a framework based on metacommunity theory and Jost's diversity estimates.Results Our results suggest three vertical patterns for neotropical butterfly communities: (a) a strong partitioning of canopy and understorey subcommunities, with distinct resulting diversity profiles; (b) greater spatial similarity for the canopy assemblages compared to the understorey (both locally and regionally); and (c) steeper distance-decay patterns for understorey assemblages compared to the canopy.Main Conclusions Our study shows the generality of vertical stratification diversity patterns across multiple Neotropical ecosystems, including previously unstudied montane cloud forests. It also shows that horizontal variation in community composition depends on the vertical position of taxa within Neotropical forests and is in general consistent with predictions based on species ecology and morphology.
ZNF711 is one of eleven zinc-finger genes on the X chromosome that have been associated with X-linked intellectual disability. This association is confirmed by the clinical findings in 20 new cases in addition to 11 cases previously reported. No consistent growth aberrations, craniofacial dysmorphology, malformations or neurologic findings are associated with alterations in ZNF711. The intellectual disability is typically mild and coexisting autism occurs in half of the cases. Carrier females show no manifestations. A ZNF711-specific methylation signature has been identified which can assist in identifying new cases and in confirming the pathogenicity of variants in the gene.
Bifidobacterium longum and B. infantis are pioneer colonizers of the neonatal gut and are widely used as probiotics to support infant growth, development, and disease resistance. However, commercial strains derived largely from high-income countries (HICs) may be suboptimal for infants in low- and middle-income countries (LMICs). We assembled a global genomic atlas of more than 4,000 genomes from 48 countries, increasing representation from LMICs by 12- to 17-fold. High-resolution phylogenomic and functional analyses support delineating B. longum and B. infantis as distinct species with divergent functions and epidemiological patterns. B. infantis dominates early-life microbiota in LMICs but is rarely detected in HICs. Natural B. infantis strains show extreme biogeographic stratification and predicted adaptations to local plant-glycan-rich diets and breast-milk-derived substrates, including urea and B vitamins. This genomic resource enables genome-guided selection of geographically matched strains to inform more effective probiotics and precision microbiome therapeutics for diverse infant populations.
De novo genome assembly is challenging in highly repetitive regions; however, reference-guided assemblers often suffer from bias. We propose a framework for pangenome-guided sequence assembly that can resolve short-read data in complex regions without bias towards a single reference genome. Our primary contribution is to frame the assembly as a graph traversal optimization problem, which can be implemented classically or on a quantum computer. The workflow involves first annotating pangenome graphs with estimated copy numbers for each node, then finding a path on the graph that best explains those copy numbers. On simulated data, our approach significantly reduces the number of contigs compared with de novo assemblers. While they introduce a small increase in inaccuracies, such as false joins, our optimization-based methods are competitive with current exhaustive search techniques. They are also designed to scale more efficiently as the problem size grows and will run effectively on future quantum computers; a small experiment on a real quantum device showcases this behaviour. Moreover, they are more resilient to noise in copy number estimation inherent in short-read-based assembly. We also develop novel tools for creating realistic synthetic pangenomes, aligning reads to pangenomes and for evaluating assembly quality.
Abstract Allosteric communication between non-contacting sites in proteins plays a fundamental role in biological regulation and drug action. While allosteric gain-of-function variants are known drivers of oncogene activation, the broader importance of allostery in genetic disease and protein evolution is less clear. Here, we introduce a comparative framework that disentangles functional disruption by mutations from protein destabilization. Applying this framework across diverse datasets—ranging from paired experimental measurements of abundance and activity to proteome-wide comparisons of evolutionary fitness and biophysical stability predictions—we provide evidence that allostery is a widespread cause of loss-of-function variant pathogenicity in human genetic diseases. In addition, our analyses reveal a conserved distance-dependent decay of allosteric mutational effects outside of protein active sites. As an important mechanism of pathogenicity, allostery needs to be better mapped, understood, and predicted across the human proteome.
