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© Jean-Claude Antoine
Leishmania mexicana amazonensis
Publication : Frontiers in cellular and infection microbiology

Reverse Epidemiology: An Experimental Framework to Drive Biomarker Discovery by Functional Genetic Screening Using Relevant Animal Models

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Frontiers in cellular and infection microbiology - 19 Sep 2018

Piel L, Pescher P, Späth GF

Link to Pubmed [PMID] – 30283743

Front Cell Infect Microbiol 2018;8:325

biomarker discovery remains an important challenge that needs to be revisited in light of our increasing knowledge on parasite-specific biology, notably its genome instability. In the absence of classical transcriptional regulation in these early-branching eukaryotes, fluctuations in transcript abundance can be generated by gene and chromosome amplifications, which have been linked to parasite phenotypic variability with respect to virulence, tissue tropism, and drug resistance. Conducting evolutionary experiments to study mechanisms of environmental adaptation, we recently validated the link between parasite genetic amplification and fitness gain, thus defining gene and chromosome copy number variations (CNVs) as important biomarkers. These experiments also demonstrated that long-term culture adaptation can strongly interfere with epidemiologically relevant, genetic signals, which challenges current protocols for biomarker discovery, all of which rely on expansion of clinical isolates. Here we propose an experimental framework independent of long-term culture termed “reverse” epidemiology, which applies established protocols for functional genetic screening of cosmid-transfected parasites in animal models for the identification of clinically relevant genetic loci that then inform targeted field studies for their validation as biomarkers.

https://www.ncbi.nlm.nih.gov/pubmed/30283743