LAMP: disease classification derived from layered assessment on modules and pathways in the human gene network

Abstract

Background: Classification of diseases based on genetic information is of great significance as the basis for precision medicine, increasing the understanding of disease etiology and revolutionizing personalized medicine. Much effort has been directed at understanding disease associations by constructing disease networks, and classifying patient samples according to gene expression data. Integrating human gene networks overcomes limited coverage of genes. Incorporating pathway information into disease classification procedure addresses the challenge of cellular heterogeneity across patients. Results: In this work, we propose a disease classification model LAMP, which concentrates on the layered assessment on modules and pathways. Directed human gene interactions are the foundation of constructing the human gene network, where the significant roles of disease and pathway genes are recognized. The fast unfolding algorithm identifies 11 modules in the largest connected component. Then layered networks are introduced to distinguish positions of genes in propagating information from sources to targets. After gene screening, hierarchical clustering and refined process, 1726 diseases from KEGG are classified into 18 categories. Also, it is expounded that diseases with overlapping genes may not belong to the same category in LAMP. Within each category, entropy is applied to measure the compositional complexity, and to evaluate the prospects for combination diagnosis and gene-targeted therapy for diseases. Conclusion: In this work, by collecting data from BioGRID and KEGG, we develop a disease classification model LAMP, to support people to view diseases from the perspective of commonalities in etiology and pathology. Comprehensive research on existing diseases can help meet the challenges of unknown diseases. The results provide suggestions for combination diagnosis and gene-targeted therapy, which motivates clinicians and researchers to reposition the understanding of diseases and explore diagnosis and therapy strategies.