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Doane, M. P.

Publications and source records attributed to Doane, M. P..

3 recordsLinked to original sources

Application of metagenomic sequencing to improve sessile serrated lesion detection using the faecal immunochemical test

Most population colorectal cancer (CRC) screening programs use the faecal immunochemical test (FIT), which quantifies occult haemoglobin in faeces and has proven to be effective in detecting and reducing CRC incidence and mortality. Sessile serrated lesions (SSLs) account for up to 30% of sporadic CRC, yet FIT has low sensitivity to detect them. Faecal microbial biomarkers may improve their detection, but FIT samples have not previously been used to study the SSL microbiome. We asked whether FIT samples preserve the faecal microbiome as accurately as fresh collection, and whether they can reveal a microbial signature of SSL. We first reanalysed a published dataset of paired FIT and fresh faecal samples from the same participants. Donor identity explained 63.5% of compositional variance compared with 16.7% for collection method, indicating that FIT preserves the donor-specific signature on which biomarker discovery depends. We then generated shotgun metagenomes from FIT samples of 24 adults scheduled for diagnostic colonoscopy, twelve with at least one clinically significant SSL and twelve with no neoplasia (NN) and compared each group with a published fresh faeces cohort matched on colonoscopy outcome. Collection method explained 6.3% to 7.6% of variance, and no individual species was significantly differentially abundant between methods. Between SSL and NN FIT samples, community structure did not significantly differ, and conservative differential abundance analysis returned no results. More permissive count-based models suggested a depletion of fermentative commensals in SSL. Functionally, SSL samples encoded significantly fewer KEGG orthologs and less polyamine biosynthesis capacity, while orthologs carried by several Bifidobacterium species were more abundant. Many depleted functions reflected Enterobacteriaceae gene content concentrated in a few control samples. No single feature was diagnostic on its own. A multi-feature signature, confirmed in larger cohorts and applied to samples that screening programs already collect, may increase the detection rate of SSLs.

bioinformatics↗

Bioenergetic mapping of 'healthy microbiomes' via compound processing potential imprinted in gut and soil metagenomes

Despite mounting evidence of their importance in human health and ecosystem functioning, the definition and measurement of healthy microbiomes remain unclear. More advanced knowledge exists on health associations for compounds used or produced by microbes. Environmental microbiome exposures (especially via soils) also help shape, and may supplement, the functional capacity of human microbiomes. Given the synchronous interaction between microbes, their feedstocks, and micro-environments, with functional genes facilitating chemical transformations, there exists an intriguing opportunity to examine microbiomes in terms of their capacity to process compounds relevant to human health. Here we integrate functional genomics and biochemistry frameworks to derive new quantitative measures of the potential for human gut and environmental soil metagenomes to process major compound classes (e.g., lipids, carbohydrates) and selected biomolecules (e.g., vitamins, short-chain fatty acids) linked to human health. Metagenome functional potential profile data were translated into a universal compound mapping landscape based on bioenergetic van Krevelen mapping of function-level meta-compounds and corresponding functional relative abundances, reflecting imprinted genetic capacity of microbiomes to metabolize an array of different compounds. We show that measures of compound processing potential associated with human health and disease (examining atherosclerotic cardiovascular disease, colorectal cancer, type 2 diabetes and anxious-depressive behavior case studies), and displayed seemingly predictable shifts along gradients of ecological disturbance in plant-soil ecosystems (three case studies). Ecosystem quality explained 60-92% of variation in soil metagenome compound processing potential measures in a post-mining restoration case study dataset. With growing knowledge of the varying proficiency of environmental microbiota to process human health associated compounds, we might design environmental interventions or nature prescriptions to modulate our exposures, thereby advancing microbiota-oriented approaches to human health. Compound processing potential offers a simplified, integrative approach for applying metagenomics in ongoing efforts to understand and quantify the role and linkages of microbiota in environmental- and human-health.

bioinformatics↗

Genomics to aid species delimitation and effective conservation of the Sharpnose Guitarfish (Glaucostegus granulatus)

The Sharpnose Guitarfish (Glaucostegus granulatus) is one of fifteen critically endangered Rhino Rays which has been exploited as incidental catch, leading to severe population depletions and localized disappearances. Like many chondrichthyan species, there are no species-specific time-series data available for the Sharpnose Guitarfish that can be used to calculate population reduction, partly due to a lack of species-specific reporting as well as limitations in accurate taxonomic identification. We here present the first complete mitochondrial genome and partial nuclear genome of the species and the first detail phylogenetic assessment of the species. We expect that data presented in the current manuscript will aid in accurate species-specific landing and population assessments of the species in the future and will enable conservation efforts to protect and recover remaining populations.

genomics↗