Motif Discovery through Predictive Modeling of Gene Regulation

We present MEDUSA, an integrative method for learning motif models of transcription factor binding sites by incorporating promoter sequence and gene expression data. We use a modern large-margin machine learning approach, based on boosting, to enable feature selection from the high-dimensional search space of candidate binding sequences while avoiding overfitting. At each iteration of the algorithm, MEDUSA builds a motif model whose presence in the promoter region of a gene, coupled with activity of a regulator in an experiment, is predictive of differential expression. In this way, we learn motifs that are functional and predictive of regulatory response rather than motifs that are simply overrepresented in promoter sequences. Moreover, MEDUSA produces a model of the transcriptional control logic that can predict the expression of any gene in the organism, given the sequence of the promoter region of the target gene and the expression state of a set of known or putative transcription factors and signaling molecules. Each motif model is either a $k$-length sequence, a dimer, or a PSSM that is built by agglomerative probabilistic clustering of sequences with similar boosting loss. By applying MEDUSA to a set of environmental stress response expression data in yeast, we learn motifs whose ability to predict differential expression of target genes outperforms motifs from the TRANSFAC dataset and from a previously published candidate set of PSSMs. We also show that MEDUSA retrieves many experimentally confirmed binding sites associated with environmental stress response from the literature.Comment: RECOMB 200

Abstract polymer models with general pair interactions

A convergence criterion of cluster expansion is presented in the case of an abstract polymer system with general pair interactions (i.e. not necessarily hard core or repulsive). As a concrete example, the low temperature disordered phase of the BEG model with infinite range interactions, decaying polynomially as $1/r^{d+\lambda}$ with $\lambda>0$, is studied.Comment: 19 pages. Corrected statement for the stability condition (2.3) and modified section 3.1 of the proof of theorem 1 consistently with (2.3). Added a reference and modified a sentence at the end of sec. 2.

A perturbative approach to BB decays into two π\pi mesons

The modified perturbative approach in which transverse degrees of freedom as well as Sudakov suppressions are taken into account, is applied to $B$ decays into two $\pi$ mesons. The influence of various model parameters (CKM matrix elements, $B$ decay constant, mesonic wave functions) on the results as well as short distance corrections to the weak Hamiltonian are discussed in some detail. The perturbative contributions to the $B$ decays yield branching ratios of the order of $10^{-7}\;-\;10^{-6}$ which values are well below the upper limit for the $\bar{B}^0\to\pi^+\pi^-$ branching ratio as measured by CLEO.Comment: 26 pages, RevTex, 6 figures appended (compressed and uuencode using 'uufiles'