Pathobiological Dictionary Defining Pathomics and Texture Features: Addressing Understandable AI Issues in...

AI holds strong potential for medical diagnostics, yet a lack of interpretability limits its clinical adoption. This study introduces the Pathobiological Dictionary for Liver Cancer (LCP1.0), a practical framework designed to translate complex Pathomics (PF) and Radiomics Features (RF) into clinically meaningful insights aligned with existing diagnostic workflows. QuPath and PyRadiomics, standardized according to Image Biomarker Standardisation Initiative (IBSI) guidelines, were used to extract 333 imaging features from hepatocellular carcinoma (HCC) tissue samples, including 240 PF-based-cell detection/intensity, 74 texture-RFs, and 19 RF-based first-order features. Expert-defined 1000 × 1000 µm ROIs from the public dataset excluded artifact-prone areas, and features were aggregated at the case level. Their relevance to the World Health Organization (WHO) grading system was assessed using multiple classifiers linked with feature selectors. The resulting dictionary was validated by 8 experts in oncology and pathology. In collaboration with 10 domain experts, we developed a Pathobiological dictionary of imaging features such as PFs and RF. In our study, the Variable Threshold feature selection algorithm combined with the SVM model achieved the highest five-fold cross-validation accuracy (0.80 ± 0.01, P < 0.05), selecting 20 key features-primarily clinical and pathomics traits such as Centroid, Cell Nucleus, and Cytoplasmic characteristics for survival outcome prediction. These features, particularly nuclear and cytoplasmic, were strongly associated with tumor grading and prognosis, reflecting atypia indicators like pleomorphism, hyperchromasia, and cellular orientation. The LCP1.0 provides a clinically validated bridge between AI outputs and expert interpretation, enhancing model transparency and usability. Aligning AI-derived features with clinical semantics supports the development of interpretable, trustworthy diagnostic tools for liver cancer pathology.