Date of Award
Doctor of Philosophy (PhD)
Biochemistry and Molecular Biology
Alexov , Emil
Schwartz , Charles E
Chen , Chin-Fu
Since large amounts of biological data are generated using various high-throughput technologies, efficient computational methods are important for understanding the biological meanings behind the complex data. Machine learning is particularly appealing for biological knowledge discovery. Tissue-specific gene expression and protein sumoylation play essential roles in the cell and are implicated in many human diseases. Protein destabilization is a common mechanism by which mutations cause human diseases. In this study, machine learning approaches were developed for predicting human tissue-specific genes, protein sumoylation sites and protein stability changes upon single amino acid substitutions. Relevant biological features were selected for input vector encoding, and machine learning algorithms, including Random Forests and Support Vector Machines, were used for classifier construction. The results suggest that the approaches give rise to more accurate predictions than previous studies and can provide valuable information for further experimental studies. Moreover, seeSUMO and MuStab web servers were developed to make the classifiers accessible to the biological research community.
Structure-based methods can be used to predict the effects of amino acid substitutions on protein function and stability. The nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) located at the protein binding interface have dramatic effects on protein-protein interactions. To model the effects, the nsSNPs at the interfaces of 264 protein-protein complexes were mapped on the protein structures using homology-based methods. The results suggest that disease-causing nsSNPs tend to destabilize the electrostatic component of the binding energy and nsSNPs at conserved positions have significant effects on binding energy changes. The structure-based approach was developed to quantitatively assess the effects of amino acid substitutions on protein stability and protein-protein interaction. It was shown that the structure-based analysis could help elucidate the mechanisms by which mutations cause human genetic disorders. These new bioinformatic methods can be used to analyze some interesting genes and proteins for human genetic research and improve our understanding of their molecular mechanisms underlying human diseases.
Teng, Shaolei, "PRETICTIVE BIOINFORMATIC METHODS FOR ANALYZING GENES AND PROTEINS" (2011). All Dissertations. 718.