Extracting transcriptional regulatory information from DNA microarray expression data

(cont.) As a model system, we have chosen the unicellular, photoautotrophic cyanobacteria Synechocystis sp. PCC6803 for study, as it is 1) fully sequenced, 2) has an easily manipulated input signal (light for photosynthesis), and 3) fixes carbon dioxide into the commercially interesting, biodegradable polymer polyhydroxyalkanoate (PHA). We have created DNA microarrays with [approximately]97% of the Synechocystis genome represented in duplicate to monitor the cellular transcriptional profile. These arrays are used in time-series experiments of differing light levels to measure dynamic transcriptional response to changing environmental conditions. We have developed networks of potential genetic regulatory interactions through time-series analysis based on the data from our studies. An algorithm for combining gene position information, clustering, and time-lagged correlations has been created to generate networks of hypothetical biological links. Analysis of these networks indicates that good correlation exists between the input signal and certain groups of photosynthesis- and metabolism-related genes. Furthermore, this analysis technique placed these in a temporal context, showing the sequence of potential effects from changes in the experimental conditions. This data and hypothetical interaction networks have been used to construct AutoRegressive with eXogenous input (ARX) models. These provide dynamic, state-space models for prediction of transcriptional profiles given a dynamically changing set of environmental perturbations...

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2003

Author dc:creator

• Schmitt, William A. (William Anthony), 1976-

Advisor dc:contributor.advisor

• Gregory Stephanopoulos.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/28290

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/28290