This is such a nice forum. I am impressed by the experience and enthusiasm of you guys. I just want to bring your attention to a paper we just published:
On the detection and refinement of transcription factor binding sites using ChIP-Seq data
Abstract
Coupling chromatin immunoprecipitation (ChIP) with recently developed massively parallel sequencing technologies has enabled genome-wide detection of protein-DNA interactions with unprecedented sensitivity and specificity. This new technology, ChIP-Seq, presents opportunities for in-depth analysis of transcription regulation. In this study, we explore the value of using ChIP-Seq data to better detect and refine transcription factor binding sites (TFBS). We introduce a novel computational algorithm named Hybrid Motif Sampler (HMS), specifically designed for TFBS motif discovery in ChIP-Seq data. We propose a Bayesian model that incorporates sequencing depth information to aid motif identification. Our model also allows intra-motif dependency to describe more accurately the underlying motif pattern. Our algorithm combines stochastic sampling and deterministic “greedy” search steps into a novel hybrid iterative scheme. This combination accelerates the computation process. Simulation studies demonstrate favorable performance of HMS compared to other existing methods. When applying HMS to real ChIP-Seq datasets, we find that (i) the accuracy of existing TFBS motif patterns can be significantly improved; and (ii) there is significant intra-motif dependency inside all the TFBS motifs we tested; modeling these dependencies further improves the accuracy of these TFBS motif patterns. These findings may offer new biological insights into the mechanisms of transcription factor regulation.
It is open access at
http://nar.oxfordjournals.org/cgi/co...stract/gkp1180
Our HMS program is freely available at
http://www.sph.umich.edu/csg/qin/HMS/
Please give HMS a try. I hope that you find it useful. Questions, comments, suggestions and criticisms are welcomed and can be sent to me at [email protected]. Thank you very much.
Best,
Ming
On the detection and refinement of transcription factor binding sites using ChIP-Seq data
Abstract
Coupling chromatin immunoprecipitation (ChIP) with recently developed massively parallel sequencing technologies has enabled genome-wide detection of protein-DNA interactions with unprecedented sensitivity and specificity. This new technology, ChIP-Seq, presents opportunities for in-depth analysis of transcription regulation. In this study, we explore the value of using ChIP-Seq data to better detect and refine transcription factor binding sites (TFBS). We introduce a novel computational algorithm named Hybrid Motif Sampler (HMS), specifically designed for TFBS motif discovery in ChIP-Seq data. We propose a Bayesian model that incorporates sequencing depth information to aid motif identification. Our model also allows intra-motif dependency to describe more accurately the underlying motif pattern. Our algorithm combines stochastic sampling and deterministic “greedy” search steps into a novel hybrid iterative scheme. This combination accelerates the computation process. Simulation studies demonstrate favorable performance of HMS compared to other existing methods. When applying HMS to real ChIP-Seq datasets, we find that (i) the accuracy of existing TFBS motif patterns can be significantly improved; and (ii) there is significant intra-motif dependency inside all the TFBS motifs we tested; modeling these dependencies further improves the accuracy of these TFBS motif patterns. These findings may offer new biological insights into the mechanisms of transcription factor regulation.
It is open access at
http://nar.oxfordjournals.org/cgi/co...stract/gkp1180
Our HMS program is freely available at
http://www.sph.umich.edu/csg/qin/HMS/
Please give HMS a try. I hope that you find it useful. Questions, comments, suggestions and criticisms are welcomed and can be sent to me at [email protected]. Thank you very much.
Best,
Ming
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