ORCID Profile
0000-0003-4260-5449
Current Organisation
University of Oxford
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Publisher: Cold Spring Harbor Laboratory
Date: 28-07-2019
DOI: 10.1101/716902
Abstract: The routine identification of pathogens during infection remains challenging because it relies on multiple modalities such as culture and nucleic acid lification and tests that tend to be specific for very few of an enormous number of possible infectious agents. Metagenomics promises single-test identification, but shotgun sequencing remains unwieldy and expensive or in many cases insufficiently sensitive to detect the amount of pathogen material in a clinical s le. Here we present the validation and application of Castanet , a method for metagenomic sequencing with enrichment that exploits clinical knowledge to construct a broad panel of relevant organisms for detection at low cost with sensitivity comparable to PCR. Castanet targets both DNA and RNA, works with small s le volumes, and can be implemented in a high-throughput diagnostic setting. We used Castanet to analyse plasma s les from 573 patients from the GAinS sepsis cohort and CSF s les from 243 patients from the ChiMES meningitis cohort that had been evaluated using standard clinical microbiology methods, identifying relevant pathogens in many cases where no pathogen had previously been detected. Castanet is intended for use in defining the distribution of pathogens in s les, diseases and populations, for large-scale clinical studies and for verifying the performance of routine testing regimens. By providing sequence as output, Castanet combines pathogen identification directly with subtyping and phylo-epidemiology.
Publisher: Cold Spring Harbor Laboratory
Date: 30-03-2018
DOI: 10.1101/292102
Abstract: The infrastructure challenges and costs of next-generation sequencing have been largely overcome, for many sequencing applications, by Oxford Nanopore Technologies’ portable MinION sequencer. However the question remains open whether MinION-based bacterial whole-genome sequencing (WGS) is by itself sufficient for the accurate assessment of phylogenetic and epidemiological relationships between isolates and whether such tasks can be undertaken in resource-limited settings. To investigate this question, we sequenced the genome of an isolate of Rickettsia typhi , an important and neglected cause of fever across much of the tropics and subtropics, for which only three genomic sequences previously existed. We prepared and sequenced libraries on a MinION in Vientiane, Lao PDR using v9.5 chemistry and in parallel we sequenced the same isolate on the Illumina platform in a genomics laboratory in the UK. The MinION sequence reads yielded a single contiguous assembly, in which the addition of Illumina data revealed 226 base-substitution and 5,856 in/del errors. The combined assembly represents the first complete genome sequence of a human R. typhi isolate collected in the last 50 years and differed from the genomes of existing strains collected over a 90-year time period at very few sites, and with no re-arrangements. Filtering based on the known error profile of MinION data improved the accuracy of the Nanopore-only assembly. However, the frequency of false-positive errors remained greater than true sequence ergence from recorded sequences. While Nanopore-only sequencing cannot yet recover phylogenetic signal in R. typhi , such an approach may be applicable for more erse organisms.
Publisher: Wiley
Date: 16-09-2022
DOI: 10.1002/ARCO.5274
Abstract: The causes of the Late Pleistocene extinction of most larger‐bodied animals on the Australian continent have long been controversial. This is due, in no small part, to inadequate knowledge of exactly when these species were lost from different ecosystems. The Nombe rockshelter in the highlands of Papua New Guinea is one of very few sites on Sahul with as‐yet‐unrefuted evidence for the survival of megafaunal species until more recently than 40 thousand years (ka) ago. However, our understanding of the age of this site has been based on radiocarbon dating. Here we present new U–Th ages on large marsupial specimens from the deposit and identify a range of postcranial elements to species that include the diprotodontid Hulitherium tomasettii , kangaroo Protemnodon tumbuna and thylacine Thylacinus cynocephalus . Direct U–Th ages of 27–22 ka ago on faunal remains of Protemnodon tumbuna and another large unidentified macropodid are consistent with the existing radiocarbon chronology, yet are minimum ages due to the potential for post‐depositional uptake of 238 U and stratigraphic reworking. Pollen analyses indicate perhumid, montane forests dominated by Nothofagus persisted, with minimal human disturbance from at least c.26–20 ka ago up to the terminal Pleistocene. Collagen fingerprinting (ZooMS) demonstrates the potential of protein‐based identification of megafaunal remains at Nombe in the future. This study leaves open the possibility of extended coexistence between some megafaunal species in the montane rainforests of New Guinea and intermittently visiting groups of people, and underscores the need for further investigation of the Nombe deposit. Although preliminary, these findings reinforce the view that debates regarding megafaunal extinctions on Sahul require a greater appreciation of species‐specific temporalities and the degrees of human impact on erse habitats across the continent.
Publisher: Public Library of Science (PLoS)
Date: 25-08-0009
DOI: 10.1371/JOURNAL.PNTD.0009685
Abstract: Scrub typhus (ST) and murine typhus (MT) are common but poorly understood causes of fever in Laos. We examined the spatial and temporal distribution of ST and MT, with the intent of informing interventions to prevent and control both diseases. This study included s les submitted from 2003 to 2017 to Mahosot Hospital, Vientiane, for ST and MT investigation. Serum s les were tested using IgM rapid diagnostic tests. Patient demographic data along with meteorological and environmental data from Laos were analysed. Approximately 17% of patients were positive for either ST (1,337/8,150 patients tested) or MT (1,283/7,552 patients tested). While both diseases occurred in inhabitants from Vientiane Capital, from the univariable analysis MT was positively and ST negatively associated with residence in Vientiane Capital. ST was highly seasonal, with cases two times more likely to occur during the wet season months of July-September compared to the dry season whilst MT peaked in the dry season. Multivariable regression analysis linked ST incidence to fluctuations in relative humidity whereas MT was linked to variation in temperature. Patients with ST infection were more likely to come from villages with higher levels of surface flooding and vegetation in the 16 days leading up to diagnosis. The data suggest that as cities expand, high risk areas for MT will also expand. With global heating and risks of attendant higher precipitation, these data suggest that the incidence and spatial distribution of both MT and ST will increase.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Ivo Elliott.