Evolutionary, Protein–Protein Interaction (PPI), and Domain–Domain Analyses in Huntington’s Disease

Mutations play a vital role in causing human neurodegenerative diseases such as Huntington's, Alzheimer's, and Parkinson's. A DNA section known as a CAG trinucleotide repeat is involved in the Huntingtin (HTT) mutation that leads to Huntington's disease (HD). Evolutionary, protein–protein interaction (PPI), and domain–domain interaction analysis provide new perceptions into neurodegenerative disorders and enable the prediction of the new causing proteins and their functionality associated with neurodegenerative diseases. The main objective of this study is to identify the top and associated proteins for HTT. This study is divided into three phases. In the first phase implemented the evolutionary analysis to identify the similarities at the cellular and molecular levels of Huntington’s disease-causing proteins. In the second phase applied the PPI analysis to build an HTT network which is used to identify existing associations and predict the new associations for this HTT. Finally, domain–domain analysis has been used to analyze the domains of similar proteins with newly identified associated proteins of HTT. This study reveals that brain-derived neurotrophic factor (BDNF), α-Adaptin, and Butyrylcholinesterase (BChE) are the new proteins directly and indirectly associated with Huntington’s disease. Also, this integrated analysis finally leads to personalized and precision medicine for other chronic diseases.