title: High-resolution computational models of genome binding events.
abstract: Direct physical information that describes where transcription factors, nucleosomes, modified histones, RNA polymerase II and other key proteins interact with the genome provides an invaluable mechanistic foundation for understanding complex programs of gene regulation. We present a method, joint binding deconvolution (JBD), which uses additional easily obtainable experimental data about chromatin immunoprecipitation (ChIP) to improve the spatial resolution of the transcription factor binding locations inferred from ChIP followed by DNA microarray hybridization (ChIP-Chip) data. Based on this probabilistic model of binding data, we further pursue improved spatial resolution by using sequence information. We produce positional priors that link ChIP-Chip data to sequence data by guiding motif discovery to inferred protein-DNA binding sites. We present results on the yeast transcription factors Gcn4 and Mig2 to demonstrate JBD's spatial resolution capabilities and show that positional priors allow computational discovery of the Mig2 motif when a standard approach fails.
authors.affiliation: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qi
authors.forename: Alex
authors.initials: A
authors.lastname: Rolfe
authors.forename: Kenzie D
authors.initials: KD
authors.lastname: MacIsaac
authors.forename: Georg K
authors.initials: GK
authors.lastname: Gerber
authors.forename: Dmitry
authors.initials: D
authors.lastname: Pokholok
authors.forename: Julia
authors.initials: J
authors.lastname: Zeitlinger
authors.forename: Timothy
authors.initials: T
authors.lastname: Danford
authors.forename: Robin D
authors.initials: RD
authors.lastname: Dowell
authors.forename: Ernest
authors.initials: E
authors.lastname: Fraenkel
authors.forename: Tommi S
authors.initials: TS
authors.lastname: Jaakkola
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
authors.forename: David K
authors.initials: DK
authors.lastname: Gifford
mesh_terms: D001483:Base Sequence; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D008956:Models, Chemical; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D014157:Transcription Factors / Q000737:chemistry*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004247:DNA