Biology subjects

James, R.

Publications and source records attributed to James, R..

4 recordsLinked to original sources

bioRxiv2018

Rapid statistical methods for inferring intra- and inter-hospital transmission of nosocomial pathogens from whole genome sequence data

Whole genome sequence (WGS) data for bacterial pathogens can provide evidence as to the source of nosocomial infection, and more specifically the ability to distinguish between intra- and inter-hospital transmission. This is currently achieved either through using SNP thresholds, which can lack statistical robustness, or by constructing phylogenetic trees, which can be computationally expensive and difficult to interpret. Here we compare two alternative statistical approaches using 1022 genomes of methicillin resistant Staphylococcus aureus (MRSA) clone ST22. In 71% of cases both methods predict the same hospital origin, which is also supported by the ML tree. Robust assignments are divided approximately equally between intra-hospital transmission and inter-hospital transmission. Our approaches are rapid and produce intuitive output that could inform on immediate infection control priorities, as well as providing long-term data on inter-hospital transmission networks. We discuss the strengths and weakness of our methods, and the generalisability of this approach.\n\nOne Sentence SummaryWe present rapid statistical methods for distinguishing intra- versus inter-hospital transmission of bacterial pathogens using whole genome sequence data; these methods do not require the use of SNP thresholds or the generation and interpretation of phylogenetic trees.

epidemiology↗

bioRxiv2018

Structural Basis of Broad Ebolavirus Neutralization by a Human Survivor Antibody

The structural features that govern broad-spectrum activity of broadly neutralizing, anti-ebolavirus antibodies (Abs) are currently unknown. Here we describe the first structure of a broadly neutralizing human Ab, ADI-15946, in complex with cleaved Ebola virus glycoprotein (EBOV GPCL). We find that ADI-15946 employs structural mimicry of a conserved interaction between the GP core and the glycan cap {beta}17-{beta}18 loop to inhibit infection. Both endosomal proteolysis of EBOV GP and binding of monoclonal Ab (mAb) FVM09 displace this loop, increase exposure of ADI-15946s conserved epitope and potentiate neutralization. Our work also illuminated the determinants of ADI-15946s reduced activity against Sudan virus (SUDV), and enabled rational, structure-guided engineering to enhance binding and neutralization against SUDV while retaining the parental breadth of activity.\n\nOne Sentence SummaryThe first crystal structure of a broadly active antibody against surface glycoproteins of ebolaviruses identifies a highly conserved epitope beneath the glycan cap and highlights the molecular requirements for broad ebolavirus neutralization.

immunology↗

bioRxiv2017

Extinction models of robustness for weighted ecological networks

O_LIAnalysis of ecological networks is a valuable approach to understanding the vulnerability of systems to environmental change. The tolerance of ecological networks to co-extinctions, resulting from sequences of primary extinctions, is a widely-used tool for modelling network robustness. Previously, these extinction models have been developed for and applied mostly to binary networks and recently used to predict cascades of co-extinctions in plant-pollinator networks. There is a need for robustness models that can make the most of the weighted data available and most importantly there is a need to understand how the structure of a network affects its robustness.\nC_LIO_LIHere, we developed a framework of extinction models for bipartite ecological networks (specifically plant-pollinator networks). In previous models co-extinctions occurred when nodes lost all their links, but by relaxing this rule (according to a set threshold) our models can be applied to binary and weighted networks, and can permit structurally correlated extinctions, i.e. the potential for avalanches of extinctions. We tested how the average and the range of robustness values is impacted by network structure and the impact of structurally-correlated extinctions sampling non-uniformly from the distribution of random extinction sequences.\nC_LIO_LIWe found that the way that structurally-correlated extinctions are modelled impacts the results; our two ecologically-plausible models produce opposing effects which shows the importance of understanding the model. We found that when applying the models to networks with weighted interactions, the effects are amplified and the variation in robustness increases. Variation in robustness is a key feature of these extinction models and is driven by the structural heterogeneity (i.e. the skewness of the degree distribution) of nodes (specifically, plant nodes) in the network.\nC_LIO_LIOur new framework of models enables us to calculate robustness with weighted, as well as binary, bipartite networks, and to make direct comparisons between models and between networks. This allows us to differentiate effects of the model and of the data (network structure) which is vital for those making ecological inferences from robustness models. The models can be applied to mutualistic and antagonistic networks, and can be extended to food webs.\nC_LI

ecology↗

bioRxiv2017

Genetic Identification Of A Common Collagen Disease In Puerto Ricans Via Identity-By-Descent Mapping In A Health System

Achieving confidence in the causality of a disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with genetic relatedness that also underlies extreme short stature. We link the gene, COL27A1, with a little-known genetic disease, previously thought to be rare and recessive. We demonstrate that disease manifests in both heterozygotes and homozygotes, indicating a common collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian disease.

genomics↗