Research in the Haeberlein lab focuses on combating multicellular pathogens and deciphering their cell biology. The common liver fluke Fasciola hepatica is a globally prevalent pathogen and causes fascioliasis, a Neglected Tropical Disease (NTD) in humans
Project description:
This online application allows a prioritization of potential drug targets within the inferred proteome of Fasciola hepatica and provides a list of predicted compounds to target these proteins. The pipeline allows customizing selection criteria and integrates information on:
1. transcriptional data available for life stages, cell- and tissue-types of F. hepatica
2. orthology to proteins in other parasitic flatworm species
3. gene essentiality based on knockout data from model organisms or based on the existence of a unique InterPro identifier
4. pre-selection of genes with a preferred annotation based on their InterPro domain
5. drug-drug target associations and chemical properties of predicted ligands
In the end, genes and proteins are ranked from highest to lowest overall scores.
a.) Genome of Fasciola hepatica:
PRJNA179522 (WormBase ParaSite: database version WBPS19)
b.) Transcriptomics data of different Fasciola hepatica life stages:
c.) Single-cell transcriptomics data of Fasciola hepatica adult worms:
d.) Spatial transcriptomics data of Fasciola hepatica adult worms:
For most criteria related to proteins and ligands, you have four options to customize their relevance for the overall drug target prediction. You can (1) assign weighting by means of a slider, depending on the importance you like to give to the criterion, (2) let a criterion be ignored if you consider it not relevant for your prediction, (3) define it as required, which means all proteins/compounds that do not satisfy the required feature will be removed, and (4) exclude proteins that fulfil the criterion, e.g. because you consider it disadvantageous for a drug target
The final ranking score for a protein after the selection process is then determined by calculating the sum of weighting factors for all individual criteria.
Patrice Tegni Sontia, Andreas J. Stroehlein and Simone Haeberlein: FasciolaDrugApp – an interactive tool to prioritize drugs and drug targets for the liver fluke Fasciola hepatica. Unpublished