Abstract
We describe a probabilistic model, implemented as a dynamic Bayesian network, that can be used to predict nucleosome positioning along a chromosome based on one or more genomic input tracks containing position-specific information (evidence). Previous models have either made predictions based on primary DNA sequence alone, or have been used to infer nucleosome positions from experimental data. Our framework permits the combination of these two distinct types of information. We show how this flexible framework can be used to make predictions based on either sequence-model scores or experimental data alone, or by using the two in combination to interpret the experimental data and fill in gaps. The model output represents the posterior probability, at each position along the chromosome, that a nucleosome core overlaps that position, given the evidence. This posterior probability is computed by integrating the information contained in the input evidence tracks along the entire input sequence, and fitting the evidence to a simple grammar of alternating nucleosome cores and linkers. In addition to providing a novel mechanism for the prediction of nucleosome positioning from arbitrary heterogeneous data sources, this framework is also applicable to other genomic segmentation tasks in which local scores are available from models or from data that can be interpreted as defining a probability assignment over labels at that position. The ability to combine sequence-based predictions and data from experimental assays is a significant and novel contribution to the ongoing research regarding the primary structure of chromatin and its effects upon gene regulation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Lubliner, S., Segal, E.: Modeling interactions between adjacent nucleosomes improves genome-wide predictions of nucleosome occupancy. Bioinformatics 25, 1348–1355 (2009)
Yuan, G.C., Liu, J.S.: Genomic Sequence is Highly Predictive of Local Nucleosome Depletion. PLoS Comp. Biol. 4, e13 (2008)
Segal, E., Fondufe-Mittendorf, Y., Chen, L., Thøaström, A., Field, Y., Moore, I.K., Wang, J.Z., Widom, J.: A genomic code for nucleosome positioning. Nature 44, 772–778 (2006)
Peckham, H.E., Thurman, R.E., Fu, Y., Stamatoyannopoulos, J.A., Noble, W.S., Struhl, K., Weng, Z.: Nucleosome positioning signals in genomic DNA. Genome Research 17, 1170–1177 (2007)
Wasson, T., Hartemink, A.J.: An ensemble model of competitive multi-factor binding of the genome. Genome Research 19, 2101–2112 (2009)
Yuan, G.C., Liu, Y.J., Dion, M.F., Slack, M.D., Wu, L.F., Altschuler, S.J., Rando, O.J.: Genome-scale identification of nucleosome positions in S. cerevisiae. Science 309, 626–630 (2005)
Lee, W., Tillo, D., Bray, N., Morse, R.H., Davis, R.W., Hughes, T.R., Nislow, C.: A high-resolution atlas of nucleosome occupancy in yeast. Nature Genetics 39, 1235–1244 (2007)
Yassour, M., Kaplan, T., Jaimovich, A., Friedman, N.: Nucleosome positioning from tiling microarray data. Bioinformatics 24, i139–i146 (2008)
Bilmes, J., Bartels, C.: Graphical Model Architectures for Speech Recognition. IEEE Signal Processing Magazine 22, 89–100 (2005)
Mavrich, T.N., Ioshikhes, I.P., Venters, B.J., Jiang, C., Tomsho, L.P., Qi, J., Schuster, S.C., Albert, I., Pugh, B.F.: A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. Genome Research 18, 1073–1083 (2008)
Reynolds, S.M., Bilmes, J.A., Noble, W.S.: Learning a weighted sequence model of the nucleosome core and linker yields more accurate predictions in Saccharomyces cerevisiae and Homo sapiens (in submission)
Kaplan, N., Moore, I.K., Fondufe-Mittendorf, Y., Gossett, A.J., Tillo, D., Field, Y., LeProust, E.M., Hughes, T.R., Lieb, J.D., Widom, J., Segal, E.: The DNA-encoded nucleosome organization of a eukaryotic genome. Nature 548, 362–366 (2009)
Sun, W., Xie, W., Xu, F., Grunstein, M., Li, K.-C.: Dissecting Nucleosome Free Regions by a Segmental Semi-Markov Model. PLoS One 4, e4721 (2009)
Field, Y., Kaplan, N., Fondufe-Mittendorf, Y., Moore, I.K., Sharon, E., Lubling, Y., Widom, J., Segal, E.: Distinct Modes of Regulation by Chromatin Encoded through Nucleosome Positioning Signals. PLoS Comp. Biol. 4, e1000216 (2008)
Badis, G., Chan, E.T., van Bakel, H., Pena-Castillo, L., Tillo, D., Tsui, K., Carlson, C.D., Gossett, A.J., Hasinoff, M.J., Warren, C.L., Gebbia, M., Talukder, S., Yang, A., Mnaimneh, S., Terterov, D., Coburn, D., Yeo, A.L., Yeo, Z.X., Clarke, N.D., Lieb, J.D., Ansari, A.Z., Nislow, C., Hughes, T.R.: A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Mol. Cell 32, 878–887 (2008)
Barski, A., Cuddapah, S., Cui, K., Roh, T.Y., Schones, D.E., Wang, Z., Wei, G., Chepelev, I., Zhao, K.: High-resolution profiling of histone methylations in the human genome. Cell 129, 823–837 (2007)
Schones, D.E., Cui, K., Cuddapah, S., Roh, T.Y., Barski, A., Wang, Z., Wei, G., Zhao, K.: Dynamic regulation of nucleosome positioning in the human genome. Cell 132, 887–898 (2008)
Harismendy, O., Ng, P.C., Strausberg, R.L., Wang, X., Stockwell, T.B., Beeson, K.Y., Schork, N.J., Murray, S.S., Topol, E.J., Levy, S., Frazer, K.A.: Evaluation of next generation sequencing platforms for population targeted sequencing studies. Genome Biol. 10, R32 (2009)
Teytelman, L., Özaydin, B., Zill, O., Lefrançois, P., Snyder, M., Rine, J., Eisen, M.B.: Impact of Chromatin Structures on DNA Processing for Genomic Analyses. PLoS One 4, e6700 (2009)
Dohm, J.C., Lottaz, C., Borodina, T., Himmelbauer, H.: Substantial biases in ultra-short read data sets from high-throughput DNA sequencing. Nucleic Acids Research 36, e105 (2008)
Marioni, J.C., Thorne, N.P., Tavaré, S.: BioHMM: a heterogeneous hidden Markov model for segmenting array CGH data. Bioinformatics 22, 1144–1146 (2006)
Hoffman, M.M., Buske, O.J., Bilmes, J.A., Noble, W.S.: Segway: a dynamic Bayesian network method for segmenting genomic data (in preparation)
Reynolds, S.M., Käll, L., Riffle, M.E., Bilmes, J.A., Noble, W.S.: Transmembrane topology and signal peptide prediction using dynamic Bayesian networks. PLoS Comp. Biol. 4, e1000213 (2008)
Bilmes, J., Zweig, G.: The Graphical Models Toolkit: An Open Source Software System for Speech and Time-Series Processing. In: Proceedings of the IEEE International Conference on Acoustics, Speech, and Signal Processing. IEEE Press, New York (2002)
Pearl, J.: Probabilistic Reasoning in Intelligent Systems: Networks of Plausible Inference. Morgan Kaufmann, San Francisco (1988)
Reynolds, S.M., Bilmes, J.A.: Part-of-speech tagging using virtual evidence and negative training. In: Proc. HLT and EMNLP, pp. 459–466. IEEE Press, New York (2005)
Granek, J.A., Clarke, N.D.: Explicit equilibrium modeling of transcription-factor binding and gene regulation. Genome Biol. 6, R87 (2005)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Reynolds, S.M., Weng, Z., Bilmes, J.A., Noble, W.S. (2010). Predicting Nucleosome Positioning Using Multiple Evidence Tracks. In: Berger, B. (eds) Research in Computational Molecular Biology. RECOMB 2010. Lecture Notes in Computer Science(), vol 6044. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-12683-3_29
Download citation
DOI: https://doi.org/10.1007/978-3-642-12683-3_29
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-12682-6
Online ISBN: 978-3-642-12683-3
eBook Packages: Computer ScienceComputer Science (R0)