Fasciola hepatica genome re-annotation and validation of selected gene models

Fasciolosis is caused by liver flukes: F. hepatica, and a sister species – F. gigantica. A growing concern with controlling the disease is resistance to triclabendazole (TCBZ), the only drug shown to kill both adult and immature liver flukes. Currently, F. hepatica mechanism of resistance to TCBZ is not clearly understood and there is no effective commercially available vaccine. Previous work proposed three mechanisms associated with TCBZ mode of action and resistance: tubulin binding activity, drug uptake mechanisms, and drug metabolism mechanism. Exploring evolutionary forces acting on F. hepatica genes associated with TCBZ mode of action and resistance could explain how the parasite develops resistance to the drug, enable identification of potential drug targets, and facilitate development of new
drugs.

A re-annotation of the current F. hepatica genome was done using an updated version of
the published F. hepatica draft genome (assembly GCA_000947175.1, BioProject PRJEB6687). Subsequently, the current annotation (Fasciola_10x_pilon, GCA_900302435.1 WormBase Parasite Version 15) was compared and critically assessed with the newly reannotated version. Using coding sequences (CDS) of three well-described annotated gene families, manual validation of the annotation was done. A total of 15,879 F. hepatica genes were identified in this project compared to the 9,401 genes in the current annotation, while differences noticed in both annotations include gene fragmentation, missing exons, and missing genes.