Date of Award

12-2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Computing

Committee Chair

Chaoyang Zhang

Committee Chair Department

Computing

Committee Member 2

Dia Ali

Committee Member 2 Department

Computing

Committee Member 3

Nan Wang

Committee Member 3 Department

Computing

Committee Member 4

Jonathan Sun

Committee Member 4 Department

Computing

Committee Member 5

Jiu Ding

Committee Member 5 Department

Mathematics

Abstract

Microarray data is a valuable source for gene regulatory network analysis. Using earthworm microarray data analysis as an example, this dissertation demonstrates that a bioinformatics-guided reverse engineering approach can be applied to analyze time-series data to uncover the underlying molecular mechanism. My network reconstruction results reinforce previous findings that certain neurotransmitter pathways are the target of two chemicals - carbaryl and RDX. This study also concludes that perturbations to these pathways by sublethal concentrations of these two chemicals were temporary, and earthworms were capable of fully recovering. Moreover, differential networks (DNs) analysis indicates that many pathways other than those related to synaptic and neuronal activities were altered during the exposure phase.

A novel differential networks (DNs) approach is developed in this dissertation to connect pathway perturbation with toxicity threshold setting from Live Cell Array (LCA) data. Findings from this proof-of-concept study suggest that this DNs approach has a great potential to provide a novel and sensitive tool for threshold setting in chemical risk assessment. In addition, a web-based tool “Web-BLOM” was developed for the reconstruction of gene regulatory networks from time-series gene expression profiles including microarray and LCA data. This tool consists of several modular components: a database, the gene network reconstruction model and a user interface. The Bayesian Learning and Optimization Model (BLOM), originally implemented in MATLAB, was adopted by Web-BLOM to provide an online reconstruction of large-scale gene regulation networks. Compared to other network reconstruction models, BLOM can infer larger networks with compatible accuracy, identify hub genes and is much more computationally efficient.

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