GENE PRIORITIZATION BY INTEGRATED ANALYSIS OF STRUCTURAL AND FUNCTIONAL PROTEIN- PROTEIN INTERACTION NETWORK OF NEUROLOGICAL DISORDERS

Abstract

Common neurological disorders show similar phenotypic manifestations like anxiety, depression and cognitive impairment. There is a need to identify shared genetic markers and molecular pathways that lead to these comorbid conditions. The present study aims to prioritize novel genetic markers that might increase the susceptibility of patients affected with one neurological disorder to other diseases as well. Identification of pathways involving such candidate markers that trigger similar clinical manifestations will help develop better and individualistic treatments for patients affected with neurological disorders. This systems biology study for the first time uses structural protein descriptors to analyse protein properties in a neurological protein interaction network. Results of protein prioritization by machine learning imply that XIAP (X-linked inhibitor of apoptosis), which is previously not known to be involved directly in neurological disorders, might be an important candidate for such diseases. These results are further validated when XIAP is characterized as an important hub and essential protein in neurological disease interaction network. It is also shown to be involved in more than one molecular pathways of neurological disorders. Therefore, structural and functional analysis of neurological protein-protein interaction network for prioritizing novel neurological candidates, proposes that XIAP, might be a significant genetic marker for neurological studies. This is an important finding, and results from this study can be used for further analysis and validation.