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Recent advances in high-throughput experimental methods in molecular
biology hold great promise. DNA microarray technologies enable
researchers to measure the expression levels of thousands of genes
simultaneously, and more recently microarrays have been exploited
to measure genome-wide protein-DNA binding events. Time series
expression data offer particularly rich opportunities for understanding
the dynamics of biological processes. However, DNA expression
data is noisy and often many data points are missing. Time series
expression data add additional complications, including sampling
rate differences between experiments and variations in the timing
of biological processes. Thus, principled computational methods
are required in order to make full use of time series expression
data.
In this talk, I will present algorithms for analyzing time series
expression data at two different levels: individual genes and
genetic regulatory networks. For the first level, I will present
algorithms that permit the principled estimation of unobserved
time-points,clustering and the identification of differentially
expressed genes. By applying these algorithms, we provide new
insights into the role of two key cell transcriptional factors.
For the network level, I will describe a new algorithm that efficiently
combines complementary large-scale expression and protein-DNA
binding data to discover co-regulated modules of genes. The discovered
modules are used to build a regulatory network of transcription
factors and modules, to label transcription factors as activators
or repressors and to identify patterns of combinatorial regulation.
Finally, I will present an algorithm which combines the above
methods to automatically infer dynamic sub-networks for specific
biological processes.
This talk is designed to be accessible to computer scientists.
No prior biological knowledge will be assumed.
Monday, March 31, 2003
337 Towne Building
1:30 - 3:00 p.m.
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