Overview

Project title
An atlas of blood regulators of liver fibrosis during schistosomiasis

People involved
Principal investigator : Dr Justin Nono
Student: Severin Kamdem
Bioinformatics support team: Katie Lennard

Short description of project
Schistosomiasis is the most debilitating human helminthiasis. Whereas the acute phase of the disease can afflict individuals at first exposure, chronic schistosomiasis is a more frequent and severe form of the disease in endemic areas which affects individuals that have repeatedly been exposed to schistosomes. In such endemic areas, constant re-infection and the ensuing poorly symptomatic course of the disease at early stages undermine the benefits of available control strategy of which chemotherapy with praziquantel is the core component. Moreover, tissue fibroproliferative pathology consequent to chronic schistosomiasis which is not fully reversed by praziquantel treatment leaves most exposed individuals with a long-lasting-to-persistent impairment of the affected organ function. The development of alternative therapeutic measures that would integrate the control of fibroproliferative pathology upon infection with schistosomes is therefore desperately needed as this would provide more efficient means to achieve the elimination of the disease burden. For this, a fine knowledge of the molecular bases of tissue pathology during schistosomiasis is therefore crucial.

In the present project funded by the European Union Clinical Trial Partnership, the UK Royal Society and the African Academy of Science, we question whether the onset / progression of tissue fibroproliferative pathology during schistosomiasis is individual-specific i.e. whether intrinsic parameters of a given host would make him/her more/less likely than others develop tissue fibrosis following schistosomiasis infection?

As a working hypothesis, mostly given our preliminary observations, we postulate that the gene expression profile of an individual would determine his/her likelihood to develop fibroproliferative pathology during schistosomiasis.

The overall objective of our study is therefore to unequivocally establish a gene expression profile that trigger/promote susceptibility to liver fibrosis during hepatointestinal schistosomiasis and in so doing generate a comprehensive database of druggable fibrosis-regulating factors. If proven determinant, the ultimate hope will be to be able to target/use identified factors to control schistosomiasis and tissue fibrosis.

Illumina RNA sequencing reads have been generated i.e. up to 45 million reads per sample for a total of 40 samples (to be clustered in 4 groups of 10 for analyses). The aim is to examine gene expression in the blood of children with vs. without liver fibrosis during schistosomiasis

Objectives
Preprocessing and downstream analysis of Ilumina .fastq reads using the nf-core/RNAseq pipeline https://github.com/kviljoen/RNAseq