Integrated Graph-Based Models Unveil Carbonic Anhydrase VIII, X, XI Expression in Cancer and Neurological Diseases

Carbonic anhydrases are metalloenzymes found both in vertebrates and invertebrates. The CAs catalyze the reversible hydration of CO2 to bicarbonate and H+ ions and play a significant role in respiration, transport of CO2, pH homeostasis, electrolyte secretion, and biosynthetic reactions. The enzymatic activity of CAs is due to the coordination of Zn2+ in the active site by three histidine residues; however, in humans, there are three CAs known as CA-related proteins (CARPs) that are catalytically inactive due to the absence of one or more of the three histidine residues required for the coordination of the Zn2+ in the active site. Studies have shown that CARPs are expressed in all parts of the brain and are overexpressed in some cancers suggesting that the CARPs play a crucial role in neurological disorders and the development of cancer. However, the precise physiological roles of CARPs are still an enigma. Therefore, in the present study, we present an end-to-end biological workflow utilizing various methodologies involving statistical procedures to compute similarity across the CARPs by assessing the occurrence of biological parameters shared across them and determining potential biomarkers in the form of transcription factors, coexpressed genes, and phenotypes, respectively, which could have possible expression levels to activate the CARPs activity along the disease pathways. Additionally, we proposed a One Health model by analyzing various drugs and chemical candidates that would have potential therapeutic effects in suppressing the biomarkers associated with disease development, hence providing a therapeutic response against the negative modulation of CARPs within humans.