Motif Discovery through Predictive Modeling of Gene Regulation

Details Motif Discovery through Predictive Modeling of Gene Regulation Motif Discovery through Predictive Modeling of Gene Regulation

2007-01-15

arxiv.org/abs/q-bio/0701021v1

Research in Computational Molecular Biology 2005

Biology

Quantitative Biology

Genomics

RECOMB 2005

Scientific paper

10.1007/11415770_41

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.

Affiliated with

Also associated with

No associations

Rating

Motif Discovery through Predictive Modeling of Gene Regulation does not yet have a rating. At this time, there are no reviews or comments for this scientific paper.

If you have personal experience with Motif Discovery through Predictive Modeling of Gene Regulation, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Motif Discovery through Predictive Modeling of Gene Regulation will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFWR-SCP-O-585585