Potential and limits of in silico target discovery - Case study of the search for new antimalarial chemotherapeutic targets.

In medical sciences, a target is a broad concept to qualify a biological entity and/or a biological phenomenon, on which one aims to act as part of a therapy. It follows that a target can be defined as a phenotype, a biological process, a subcellular organelle, a protein or a protein domain. It also follows that a target cannot be defined independently of the type of intervention one considers implementing. In this brief review, we describe how in silico organization of genomic and post-genomic information of all partners involved in malaria (human patient, Plasmodium parasite and Anopheles vector), complying with knowledge of the disease in etiologic terms, appears as an efficient source of information not only to help selecting but also discarding target candidates. Some limitations in our capacity to explore the stored biological information, due to the current quality of genomic annotation, level of database integration, or to the performances of existing analytic and mining tools, are discussed. In silico strategies to assess the feasibility of bringing a target to a therapeutic development pipeline, in terms of target "druggability", are introduced.