Theory and practice in biomedical informatics: a framework for discovery

OBJECTIVE: Clarify disciplinary foundations and internal structure of biomedical informatics. METHODS: We analyze BMI's emergence at disciplinary intersections and map its internal structure across 4 domains: theory and practice of knowledge discovery, knowledge representation and reasoning, knowledge architecture, and knowledge-driven transformation. We compare BMI with mathematics, computer science, biostatistics, and biomedical engineering, and illustrate emergent characteristics through a precision medicine example. RESULTS: BMI's distinctive contribution-elucidating the structure of biomedical knowledge and developing methods to discover, preserve, and make knowledge actionable-requires strength across all 4 domains. BMI developed these domains pragmatically: building systems, extracting principles, and formalizing theories. The discipline must now complement empirical approaches with rigorous theoretical work: assessing adequacy of existing theories, identifying gaps, and orchestrating collaborative development. CONCLUSIONS: BMI creates emergent capabilities across disciplines. As biomedicine becomes increasingly complex, BMI must strengthen its theoretical foundations while demonstrating transformative potential of knowledge spanning biological scales and time.