Wellcome Trust Sanger Institute

About: Wellcome Trust Sanger Institute is a nonprofit organization based out in Cambridge, United Kingdom. It is known for research contribution in the topics: Population & Genome. The organization has 4009 authors who have published 9671 publications receiving 1224479 citations.

New approaches for unravelling reassortment pathways

Abstract: Every year the human population encounters epidemic outbreaks of influenza, and history reveals recurring pandemics that have had devastating consequences. The current work focuses on the development of a robust algorithm for detecting influenza strains that have a composite genomic architecture. These influenza subtypes can be generated through a reassortment process, whereby a virus can inherit gene segments from two different types of influenza particles during replication. Reassortant strains are often not immediately recognised by the adaptive immune system of the hosts and hence may be the source of pandemic outbreaks. Owing to their importance in public health and their infectious ability, it is essential to identify reassortant influenza strains in order to understand the evolution of this virus and describe reassortment pathways that may be biased towards particular viral segments. Phylogenetic methods have been used traditionally to identify reassortant viruses. In many studies up to now, the assumption has been that if two phylogenetic trees differ, it is because reassortment has caused them to be different. While phylogenetic incongruence may be caused by real differences in evolutionary history, it can also be the result of phylogenetic error. Therefore, we wish to develop a method for distinguishing between topological inconsistency that is due to confounding effects and topological inconsistency that is due to reassortment. The current work describes the implementation of two approaches for robustly identifying reassortment events. The algorithms rest on the idea of significance of difference between phylogenetic trees or phylogenetic tree sets, and subtree pruning and regrafting operations, which mimic the effect of reassortment on tree topologies. The first method is based on a maximum likelihood (ML) framework (MLreassort) and the second implements a Bayesian approach (Breassort) for reassortment detection. We focus on reassortment events that are found by both methods. We test both methods on a simulated dataset and on a small collection of real viral data isolated in Hong Kong in 1999. The nature of segmented viral genomes present many challenges with respect to disease. The algorithms developed here can effectively identify reassortment events in small viral datasets and can be applied not only to influenza but also to other segmented viruses. Owing to computational demands of comparing tree topologies, further development in this area is necessary to allow their application to larger datasets.

The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants.

Abstract: Background Stenotrophomonas maltophilia is a nosocomial opportunistic pathogen of the Xanthomonadaceae. The organism has been isolated from both clinical and soil environments in addition to the sputum of cystic fibrosis patients and the immunocompromised. Whilst relatively distant phylogenetically, the closest sequenced relatives of S. maltophilia are the plant pathogenic xanthomonads.

A unified catalog of 204,938 reference genomes from the human gut microbiome.

Abstract: Comprehensive, high-quality reference genomes are required for functional characterization and taxonomic assignment of the human gut microbiota. We present the Unified Human Gastrointestinal Genome (UHGG) collection, comprising 204,938 nonredundant genomes from 4,644 gut prokaryotes. These genomes encode >170 million protein sequences, which we collated in the Unified Human Gastrointestinal Protein (UHGP) catalog. The UHGP more than doubles the number of gut proteins in comparison to those present in the Integrated Gene Catalog. More than 70% of the UHGG species lack cultured representatives, and 40% of the UHGP lack functional annotations. Intraspecies genomic variation analyses revealed a large reservoir of accessory genes and single-nucleotide variants, many of which are specific to individual human populations. The UHGG and UHGP collections will enable studies linking genotypes to phenotypes in the human gut microbiome.

Citrobacter rodentium of mice and man

Abstract: The major classes of enteric bacteria harbour a conserved core genomic structure, common to both commensal and pathogenic strains, that is most likely optimized to a life style involving colonization of the host intestine and transmission via the environment. In pathogenic bacteria this core genome framework is decorated with novel genetic islands that are often associated with adaptive phenotypes such as virulence. This classical genome organization is well illustrated by a group of extracellular enteric pathogens, which includes enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli (EHEC) and Citrobacter rodentium, all of which use attaching and effacing (A/E) lesion formation as a major mechanism of tissue targeting and infection. Both EHEC and EPEC are poorly pathogenic in mice but infect humans and domestic animals. In contrast, C. rodentium is a natural mouse pathogen that is related to E. coli, hence providing an excellent in vivo model for A/E lesion forming pathogens. C. rodentium also provides a model of infections that are mainly restricted to the lumen of the intestine. The mechanism's by which the immune system deals with such infections has become a topic of great interest in recent years. Here we review the literature of C. rodentium from its emergence in the mid-1960s to the most contemporary reports of colonization, pathogenesis, transmission and immunity.