Data-Driven Insights into the Association Between Oxidative Stress and Calcium-Regulating Proteins in Cardiovascular Disease.

A growing body of biomedical literature suggests a bidirectional regulatory relationship between cardiac calcium (Ca²⁺)-regulating proteins and reactive oxygen species (ROS) that is integral to the pathogenesis of various cardiac disorders via oxidative stress (OS) signaling. To address the challenge of finding hidden connections within the growing volume of biomedical research, we developed a data science pipeline for efficient data extraction, transformation, and loading. Employing the CaseOLAP (Context-Aware Semantic Analytic Processing) algorithm, our pipeline quantifies interactions between 128 human cardiomyocyte Ca²⁺-regulating proteins and eight cardiovascular disease (CVD) categories. Our machine-learning analysis of CaseOLAP scores reveals that the molecular interfaces of Ca²⁺-regulating proteins uniquely associate with cardiac arrhythmias and diseases of the cardiac conduction system, distinguishing them from other CVDs. Additionally, a knowledge graph analysis identified 59 of the 128 Ca²⁺-regulating proteins as involved in OS-related cardiac diseases, with cardiomyopathy emerging as the predominant category. By leveraging a link prediction algorithm, our research illuminates the interactions between Ca²⁺-regulating proteins, OS, and CVDs. The insights gained from our study provide a deeper understanding of the molecular interplay between cardiac ROS and Ca²⁺-regulating proteins in the context of CVDs. Such an understanding is essential for the innovation and development of targeted therapeutic strategies.