The oral and gut microbiome dynamics in patients with advanced biliary tract cancer

Biliary tract cancers (BTCs) are are a relatively rare and diverse group of cancers developing from bile ducts (cholangiocarcinoma) and the gallbladder (gallbladder carcinoma). Unfortunately, biliary tract cancers are most often diagnosed at an advanced stage, and carry a dismal prognosis, thus being an area of high unmet medical need. The main treatment for both resected and advanced BTC remains cytotoxic chemotherapy, however we lack biomarkers to predict who will benefit from this treatment. There is emerging evidence that gut or oral microbial 'signatures' (that is- patterns of microbial abundances) might have prognostic or predictive biomarker value, however this needs validation in larger cohorts. To address this, in collaboration with The Christie Hospital (Manchester, UK) and the Wellcome Sanger Institute (Hinxton, UK), we have performed shotgun metagenomic sequencing of longitudinal paired stool and saliva samples from the EMBRACER cohort study (total 130 samples from n=50 patients with BTC). This includes samples prior to and after commencement of cytotoxic chemotherapy. This honours or masters project would involve the analysis of this dataset to address the following key questions: 1. Can gut and/or oral microbial constituents (for example, species-level taxonomic abundances, or functional pathway abundances) predict clinical outcomes for patients with BTCs? 2. Is chemotherapy associated with generalisable changes in the gut and/or oral microbiome, including the emergence of anti-microbial resistance? 3. Does oral-gut translocation occur after initiation of chemotherapy for BTCs? The student would hone skills in the analysis of metagenomic sequencing data using both read-based and assembly-based approaches, as well as downstream microbial data analysis, primarily in the R coding environment.