Deciphering the Molecular Mechanism Underlying African Animal Trypanosomiasis by Means of the 1000 Bull Genomes Project Genomic Dataset

Abstract

African Animal Trypanosomiasis (AAT) is a neglected tropical disease and spreads by the vector tsetse fly, which carries the infectious Trypanosoma sp. in their saliva. Particularly, this parasitic disease affects the health of livestock, thereby imposing economic constraints on farmers, costing billions of dollars every year, especially in sub-Saharan African countries. Mainly considering the AAT disease as a multistage progression process, we previously performed upstream analysis to identify transcription factors (TFs), their co-operations, over-represented pathways and master regulators. However, downstream analysis, including effectors, corresponding gene expression profiles and their association with the regulatory SNPs (rSNPs), has not yet been established. Therefore, in this study, we aim to investigate the complex interplay of rSNPs, corresponding gene expression and downstream effectors with regard to the AAT disease progression based on two cattle breeds: trypanosusceptible Boran and trypanotolerant N’Dama. Our findings provide mechanistic insights into the effectors involved in the regulation of several signal transduction pathways, thereby differentiating the molecular mechanism with regard to the immune responses of the cattle breeds. The effectors and their associated genes (especially MAPKAPK5, CSK, DOK2, RAC1 and DNMT1) could be promising drug candidates as they orchestrate various downstream regulatory cascades in both cattle breeds.

Comparative Investigation of Coincident Single Nucleotide Polymorphisms Underlying Avian Influenza Viruses in Chickens and Ducks

“…To gain more insight into the functional role of candidate genes in the initiation, modulation, and resolution of immune responses to AIVs, we identified key signaling pathways and effector molecules using candidate genes for both chickens and ducks. Effectors are crucial signaling molecules that act as end products located several steps downstream and regulate the function of numerous signaling cascades [69]. In the context of AIVs, exploring and understanding the role of effectors in association with coSNPs and their corresponding candidate genes could provide important knowledge for unraveling effective or perturbed immune responses.…”

“…In the context of AIVs, exploring and understanding the role of effectors in association with coSNPs and their corresponding candidate genes could provide important knowledge for unraveling effective or perturbed immune responses. Similar to the previous study by Rajavel et al [69], we performed an effector molecule search for both the chicken and the duck gene list on the bioinformatics platform geneXplain [70] using the TRANSPATH ® database [71]. Recommended parameters of the effector search workflow were set according to Rajavel et al [69] with a maximum search radius of 10, a FDR adjusted p-value < 0.05 and a z-score > 1.0.…”

“…Similar to the previous study by Rajavel et al [69], we performed an effector molecule search for both the chicken and the duck gene list on the bioinformatics platform geneXplain [70] using the TRANSPATH ® database [71]. Recommended parameters of the effector search workflow were set according to Rajavel et al [69] with a maximum search radius of 10, a FDR adjusted p-value < 0.05 and a z-score > 1.0. Furthermore, we employed a pathway enrichment search using the Reactome database [72] and an FDR adjusted p-value < 0.05 to check if a pathway is mainly affected by our genes.…”