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A traceable biomarker is a member of a disease's molecular pathway. A disease may be associated with several molecular pathways. Each different combination of these molecular pathways, to which detected traceable biomarkers belong, may serve as an indicative of the elicitation of the disease at a different time frame in the future. Based on this notion, we introduce a novel methodology for personalizing an individual's degree of future susceptibility to a specific disease. We implemented the methodology in a working system called Susceptibility Degree to a Disease Predictor (SDDP). For a specific disease d, let S be the set of molecular pathways, to which traceable biomarkers detected from most patients of d belong. For the same disease d, let S' be the set of molecular pathways, to which traceable biomarkers detected from a certain individual belong. SDDP is able to infer the subset S'' ⊆{S-S'} of undetected molecular pathways for the individual. Thus, SDDP can infer undetected molecular pathways of a disease for an individual based on few molecular pathways detected from the individual. SDDP can also help in inferring the combination of molecular pathways in the set {S'+S''}, whose traceable biomarkers collectively is an indicative of the disease. SDDP is composed of the following four components: information extractor, interrelationship between molecular pathways modeler, logic inferencer, and risk indicator. The information extractor takes advantage of the exponential increase of biomedical literature to automatically extract the common traceable biomarkers for a specific disease. The interrelationship between molecular pathways modeler models the hierarchical interrelationships between the molecular pathways of the traceable biomarkers. The logic inferencer transforms the hierarchical interrelationships between the molecular pathways into rule-based specifications. It employs the specification rules and the inference rules for predicate logic to infer as many as possible undetected molecular pathways of a disease for an individual. The risk indicator outputs a risk indicator value that reflects the individual's degree of future susceptibility to the disease. We evaluated SDDP by comparing it experimentally with other methods. Results revealed marked improvement.

Citation

Kamal Taha, Ramana Davuluri, Paul Yoo, Jesse Spencer. Personizing the prediction of future susceptibility to a specific disease. PloS one. 2021;16(1):e0243127

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PMID: 33406077

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