Machine Learning Approaches to Gene Duplication and Transcription Regulation
Candidate: Huang-Wen Chen
Advisor: Dennis Shasha

Abstract

Gene duplication can lead to genetic redundancy or functional divergence, when duplicated genes evolve independently or partition the original function. In this dissertation, we employed machine learning approaches to study two different views of this problem: 1) Redundome, which explored the redundancy of gene pairs in the genome of Arabidopsis thaliana, and 2) ContactBind, which focused on functional divergence of transcription factors by mutating contact residues to change binding affinity.

In the Redundome project, we used machine learning techniques to classify gene family members into redundant and non-redundant gene pairs in Arabidopsis thaliana, where sufficient genetic and genomic data is available. We showed that Support Vector Machines were two-fold more precise than single attribute classifiers, and performed among the best within other machine learning algorithms. Machine learning methods predict that about half of all genes in Arabidopsis showed the signature of predicted redundancy with at least one but typically less than three other family members. Interestingly, a large proportion of predicted redundant gene pairs were relatively old duplications (e.g., Ks>1), suggesting that redundancy is stable over long evolutionary periods. The genome-wide predictions were plot with similarity trees based on ClustalW alignment scores, and can be accessed at http://redundome.bio.nyu.edu.

In the ContactBind project, we use Bayesian networks to model dependences between contact residues in transcription factors and binding site sequences. Based on the models learned from various binding experiments, we predicted binding motifs and their locations on promoters for three families of transcription factors in three species. The predictions are publicly available at http://contactbind.bio.nyu.edu. The website also provides tools to predict binding motifs and their locations for novel protein sequences of transcription factors. Users can construct their Bayesian networks for new families once such a familial binding data is available.