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Frizelle, F. A.

Publications and source records attributed to Frizelle, F. A..

3 recordsLinked to original sources

MetaFunc: Taxonomic and Functional Analyses of High Throughput Sequencing for Microbiomes

The identification of functional processes taking place in microbiome communities augment traditional microbiome taxonomic studies, giving a more complete picture of interactions taking place within the community. While there are applications that perform functional annotation on metagenomes or metatranscriptomes, very few of these are able to link taxonomic identity to function or are limited by their input types or databases used. Here we present MetaFunc, a workflow which takes input reads, and from these 1) identifies species present in the microbiome sample and 2) provides gene ontology (GO) annotations associated with the species identified. In addition, MetaFunc allows for host gene analysis, mapping the reads to a host genome, and separating these reads, prior to microbiome analyses. Differential abundance analysis for microbe taxonomies, and differential gene expression analysis and gene set enrichment analysis may then be carried out through the pipeline. A final correlation analysis between microbial species and host genes can also be performed. Finally, MetaFunc builds an R shiny application that allows users to view and interact with the microbiome results. In this paper, we showed how MetaFunc can be applied to metatranscriptomic datasets of colorectal cancer.

bioinformatics

Molecular subtyping improves prognostication of Stage 2 colorectal cancer

Post-surgical staging is the mainstay of prognostic stratification for colorectal cancer (CRC). Here, we compare TNM staging to consensus molecular subtyping (CMS) and assess the value of subtyping in addition to stratification by TNM. Three hundred and eight treatment-naive colorectal tumours were accessed from our institutional tissue bank. CMS was carried out using tumour gene-expression data. Staging and CMS were analysed with respect to clinicopathologic variables and patient outcome. CMS alone was not associated with survival, while TNM stage significantly explained mortality. Addition of CMS to TNM-stratified tumours showed a prognostic effect in stage 2 tumours; CMS3 tumours had a significantly lower overall survival (P = 0.006). Stage 2 patients with a good prognosis showed immune activation and up-regulation of tumour suppressor genes. Although stratification using CMS does not outperform TNM staging as a prognostic indicator, gene-expression based subtyping shows promise for improved prognostication in stage 2 CRC.

cancer biology

Distinct gut microbiome patterns associate with consensus molecular subtypes of colorectal cancer

Colorectal cancer (CRC) is a heterogeneous disease and recent advances in subtype classification have successfully stratified the disease using molecular profiling. The contribution of bacterial species to CRC development is increasingly acknowledged, and here, we sought to analyse CRC microbiomes and relate them to tumour consensus molecular subtypes (CMS), in order to better understand the relationship between bacterial species and the molecular mechanisms associated with CRC subtypes. We classified 34 tumours into CRC subtypes using RNA-sequencing derived gene expression and determined relative abundances of bacterial taxonomic groups using 16S rRNA amplicon metabarcoding. 16S rRNA analysis showed enrichment of Fusobacteria and Bacteroidetes, and decreased levels of Firmicutes and Proteobacteria in CMS1. A more detailed analysis of bacterial taxa using non-human RNA-sequencing reads uncovered distinct bacterial communities associated with each molecular subtype. The most highly enriched species associated with CMS1 included Fusobacterium hwasookii and Porphyromonas gingivalis. CMS2 was enriched for Selenomas and Prevotella species, while CMS3 had few significant associations. Targeted quantitative PCR validated these findings and also showed an enrichment of Fusobacterium nucleatum, Parvimonas micra and Peptostreptococcus stomatis in CMS1. In this study, we have successfully associated individual bacterial species to CRC subtypes for the first time.

cancer biology