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Abstracts (2003)
Y. Barash, G. Elidan, N. Friedman and T. Kaplan
Modeling Dependencies in Protein-DNA Binding Sites
In Proc. Fifth Annual Inter. Conf. on Computational Molecular Biology (RECOMB), 2003.
Supplementary Data,
The recent growth in genomic data and measurement of genome-wide expression patterns allows to examine gene regulation by transcription factors using computational tools. In this work, we present a class of mathematical models that help in understanding the connections between transcription factors and functional classes of genes based on genetic and genomic data. These models represent the joint distribution of transcription factor binding sites and of expression levels of a gene in a single model. Learning a combined probability model of binding sites and expression patterns enables us to improve the clustering of the genes based on the discovery of putative binding sites and to detect which binding sites and experiments best characterize a cluster. To learn such models from data, we introduce a new search method that rapidly learns a model according to a Bayesian score. We evaluate our method on synthetic data as well as on real data and analyze the biological insights it provides.

E. Segal, M. Shapira, A. Regev, D. Pe'er, D. Botstein, and D. Koller, and N. Friedman
Module Networks: identifying regulatory modules and their condition- specific regulators from gene expression data
In Nature Genetics, 2003.

Much of a cell's activity is organized as a network of interacting modules: sets of genes coregulated to respond to different conditions. We present a probabilistic method for identifying regulatory modules from gene expression data. Our procedure identifies modules of coregulated genes, their regulators and the conditions under which regulation occurs, generating testable hypotheses in the form 'regulator X regulates module Y under conditions W'. We applied the method to a Saccharomyces cerevisiae expression data set, showing its ability to identify functionally coherent modules and their correct regulators. We present microarray experiments supporting three novel predictions, suggesting regulatory roles for previously uncharacterized proteins.

G. Elidan and N. Friedman
The Information Bottleneck EM Algorithm
In Proc. Nineteenth Conf. on Uncertainty in Artificial Intelligence (UAI), 2003.

Learning with hidden variables is a central challenge in probabilistic graphical models that has important implications for many real-life problems. The classical approach is using the Expectation Maximization (EM) algorithm. This algorithm, however, can get trapped in local maxima. In this paper we explore a new approach that is based on the Information Bottleneck principle. In this approach, we view the learning problem as a tradeoff between two information theoretic objectives. The first is to make the hidden variables uninformative about the identity of specific instances. The second is to make the hidden variables informative about the observed attributes. By exploring different tradeoffs between these two objectives, we can gradually converge on a high-scoring solution. As we show, the resulting, Information Bottleneck Expectation Maximization (IB-EM) algorithm, manages to find solutions that are superior to standard EM methods.

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