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ANR funded project

Interactions humain-machine, objets connectés, contenus numériques, données massives et connaissance (DS0707) 2015
Projet PractiKPharma

Practice-based evidences for actioning Knowledge in Pharmacogenomics

Pharmacogenomics (PGx) studies how individual gene variations cause variability in drug responses. A state of the art of PGx is available and constitutes a basis for implementing personalized medicine, i.e., a medicine tailored to each patient by considering in particular her/his genomic context. However, most of the state of the art of this domain is not yet validated, consequently not yet applicable to medicine. Indeed, most of it results from assays that do not fulfill statistics validation standards and are difficult to reproduce because of the rarity of gene variations studied (making hard to recruit sufficiently large cohorts) and of the multifactorial aspect of drug responses. Beside, the generalizing use of Electronic Health Records (or EHRs) generates large repositories that offer new opportunities such as composing patient cohorts for the study of clinical hypotheses hard to test experimentally. Typically, EHR repositories make possible to assemble cohorts of patients to study, on the basis of practice-based data, the impact of gene variations on drug responses.

The goal of the PractiKPharma project (Practice-based evidences for actioning Knowledge in Pharmacogenomics) is to validate or moderate PGx state-of-the-art (SOTA) knowledge on the basis of practice-based evidences, i.e., knowledge extracted from EHRs. Units of knowledge in PGx typically have the form of ternary relationships gene variant–drug–adverse event, and can be formalized to different extents using biomedical ontologies. To achieve our goal, we propose: (1) to extract SOTA knowledge from PGx databases and literature, (2) to extract observational knowledge (i.e., knowledge extracted from observational data) from EHRs, (3) to compare knowledge units extracted from these two origins, to confirm or moderate SOTA knowledge, with the ultimate goal of enabling personalized medicine. (4) Finally, we intend to emphasize confirmed knowledge by investigating omics databases for molecular mechanisms that underlie and explain drug adverse events. For this investigation will use and contribute to the biomedical Linked Open Data.

The PractiKPharma project involves a multidisciplinary consortium of 4 academic partners: 2 informatics experts, the LORIA of Nancy (coordinator), the LIRMM of Montpellier; and 2 biomedical experts, the HEGP (Paris) specialized in EHRs management and PGx, and the SSPIM (from CHU Saint-Etienne) specialized in medical informatics and pharmacovigilance.

The expected impacts of PractiKPharma both in computer science and in its application domain are: novel methods for knowledge extraction from text and EHRs; multilingual semantic annotation of EHRs; methods for representing and comparing SOTA and observational knowledge; a database that maps genotypes to quantitative traits to facilitate the study of PGx with EHRs; the completion and connection of Linked Open Data related to PGx; methods for hypothesizing on mechanisms of adverse events; validated PGx knowledge units. Consequently, our ultimate goal is to provide clinicians with actionable PGx knowledge to establish guidelines that, implemented in personalized medicine, will reduce drug adverse events, and then improve the quality of clinical care.

Partners

AP-HP HOPITAL EUROPEEN GEORGES POMPIDOU Département d'informatique biomédicale et de santé publique

CHU DE SAINT-ETIENNE Service de santé publique et de l'information médicale

LORIA Laboratoire Lorrain de Recherche en Informatique et ses Applications

UM-LIRMM Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier

ANR grant: 676 579 euros
Beginning and duration: octobre 2015 - 42 mois

 

ANR Programme: Interactions humain-machine, objets connectés, contenus numériques, données massives et connaissance (DS0707) 2015

Project ID: ANR-15-CE23-0028

Project coordinator:
Monsieur Adrien COULET (Laboratoire Lorrain de Recherche en Informatique et ses Applications)

 

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The project coordinator is the author of this abstract and is therefore responsible for the content of the summary. The ANR disclaims all responsibility in connection with its content.