Analysis abstract


Nature Biotechnology 24, 963 - 970 (2006)
Published online: 9 August 2006 | doi:10.1038/nbt1233



There is an Erratum (October 2006) associated with this Analysis.

High-resolution computational models of genome binding events

Yuan Qi1,6, Alex Rolfe1,6, Kenzie D MacIsaac1,6, Georg K Gerber1,2, Dmitry Pokholok3, Julia Zeitlinger3, Timothy Danford1, Robin D Dowell1, Ernest Fraenkel1,4, Tommi S Jaakkola1, Richard A Young3,5 & David K Gifford1,3


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.

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  1. MIT Computer Science and Artificial Intelligence Laboratory, 32 Vassar Street, Cambridge, Massachusetts 02139, USA.
  2. Harvard-MIT Division of Health Sciences and Technology, 45 Carleton Street Room E25-519, Cambridge, Massachusetts 02139, USA.
  3. Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.
  4. MIT Biological Engineering Division, 77 Massachusetts Ave., Cambridge, Massachusetts 02139, USA.
  5. MIT Department of Biology, 31 Ames Street Room 68-132, Cambridge, Massachusetts 02139, USA.
  6. These authors contributed equally to the work.

Correspondence to: David K Gifford1,3 e-mail: gifford@mit.edu



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