A Standardized M3Cs clinical validity framework for microRNA data in microRNA databases with application to MicroRNA Childhood Cancer Catalog (M3Cs) version 2.0

Abstract The rapid expansion of miRNA research as cancer biomarkers has spurred the development of user-friendly miRNA-disease databases. However, integrating these bioinformatics tools into clinical practice requires innovative approaches. Digital innovation (DIN) represents the innovative link to integrate proposed ‘M3Cs standardized clinical validity framework’ in digital miRNA-disease databases. Our team diligently adhered to the standard workflow of DIN, following each step of the process: Initiate, Develop, Implement, and Exploit. Here we describe a framework for the accurate and standardized clinical validity categorization of miRNAs in databases and validate it by application to the MicroRNA Childhood Cancer Catalog version 2.0 (M3Cs V.2.0) as the product of DIN. The framework provides a semiquantitative measurement for the strength of evidence of a miRNA-disease relationship that correlates to a qualitative classification: "Strong”, “Moderate”, “Limited”, "No Known Trait/Trait subtype Relationship” or "Contradictory Evidence”. Classifications derived from this framework are reviewed and confirmed or adjusted based on clinical expertise of appropriate disease experts. To our knowledge, this is the first catalog to connect miRNAs data with the clinical impact as a validated tool in childhood cancer. We believe that widespread adoption of this framework will lead to improved analysis, interpretation, and integration of miRNA data toward clinical utility.