Principled computational methods for the validation discovery of genetic regulatory networks

As molecular biology continues to evolve in the direction of high-throughput collection of data, it has become increasingly necessary to develop computational methods for analyzing observed data that are at once both sophisticated enough to capture essential features of biological phenomena and at the same time approachable in terms of their application. We demonstrate how graphical models, and Bayesian networks in particular, can be used to model genetic regulatory networks. These methods are well-suited to this problem owing to their ability to model more than pair-wise relationships between variables, their ability to guard against over-fitting, and their robustness in the face of noisy data. Moreover, Bayesian network models can be scored in a principled manner in the presence of both genomic expression and location data. We develop methods for extending Bayesian network semantics to include edge annotations that allow us to model statistical dependencies between biological factors with greater refinement. We derive principled methods for scoring these annotated Bayesian networks. Using these models in the presence of genomic expression data requires suitable methods for the normalization and discretization of this data.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2001

Author dc:creator

• Hartemink, Alexander J. (Alexander John), 1972-

Advisor dc:contributor.advisor

• David K. Gifford.

• Electrical Engineering and Computer Science.

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

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/8699

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/8699