Modeling And Identification Of Differentially Regulated Genes Using Transcriptomics And Proteomics Data

Photosynthetic organisms are complex dynamical systems, showing a remarkable ability to adapt to different environmental conditions for their survival. Mechanisms underlying the coordination between different cellular processes in these organisms are still poorly understood. In this dissertation we utilize various computational and modeling techniques to analyze transcriptomics and proteomics data sets from several photosynthetic organisms. We try to use changes in expression levels of genes to study responses of these organisms to various environmental conditions such as availability of nutrients, concentrations of chemicals in growth media, and temperature. Three specific problems studied here are transcriptomics modifications in photosynthetic organisms under reduction-oxidation: redox) stress conditions, circadian and diurnal rhythms of cyanobacteria and the effect of incident light patterns on these rhythms, and the coordination between biological processes in cyanobacteria under various growth conditions. Under redox stresses caused by high light treatments, a strong transcriptomic level response, spread across many biological processes, is discovered in the cyanobacterium <italic>Synechocystis</italic> sp. PCC 6803. Based on statistical tests, expression levels of about 20% of genes in <italic>Synechocystis</italic> 6803 are identified as significantly affected due to influence of high light. Gene clustering methods reveal that these responses can mainly be classified as transient and consistent responses, depending on the duration of modified behaviors. Many genes related to energy production as well as energy utilization are shown to be strongly affected. Analysis of microarray data under two stress conditions, high light and DCMU treatment, combined with data mining and motif finding algorithms led to a discovery of novel transcription factor, RRTF1 that responds to redox stresses in <italic>Arabidopsis thaliana</italic>. Time course transcriptomics data from <italic>Cyanothece</italic> sp. ATCC 51142 have shown strong diurnal rhythms. By combining multiple experimental conditions and using gene classification algorithms based on Fourier scores and angular distances, it is shown that majority of the diurnal genes are in fact light responding. Only about 10% of genes in the genome are categorized as being circadian controlled. A transcription control model based on dynamical systems is employed to identify the interactions between diurnal genes. A phase oscillator network is proposed to model the behavior of different biological processes. Both these models are shown to carry biologically meaningful features. To study the coordination between different biological processes to various environment and genetic modifications, an interaction model is derived using Bayesian network approach, combining all publicly available microarray data sets for <italic>Synechocystis</italic> sp. PCC 6803. Several novel relationships between biological processes are discovered from the model. Model is used to simulate several experimental conditions, and the response of the model is shown to agree with the experimentally observed behaviors.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Electrical and Systems Engineering

Year dc:date.available

2009

Author dc:creator

• Elvitigala, Thanura

Contributors dc:contributor

• Bijoy Ghosh

• Engineering
• System Science
• Biology
• Bioinformatics
• Dynamical Systems Modeling
• Gene Regulatory Networks
• Systems Biology
• Transcriptomics and Proteomics

Language dc:language

English (en)

DOI

https://doi.org/10.7936/K76D5R1P

OAI identifier oai:identifier

oai:openscholarship.wustl.edu:etd-1099