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T-KDE introduction:
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A protein may bind to its target DNA sites constitutively, i.e., regardless of cell type. Intuitively, constitutive binding sites should be biologically functional. Knowing the locations of all constitutive sites for a protein of interest is prerequisite for understanding these sites’ functional relevance. Computational methods for identifying constitutive sites are lacking, however. We propose a method, T-KDE, to identify the locations of constitutive binding sites. T-KDE, which combines a binary range tree with a kernel density estimator, is applied to ChIP-seq data from multiple cell lines.

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T-KDE usage:
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The software is built for Mablab 7.11.0 (R2010b) on 64 bit machines.
T-KDE takes ChIP-seq peak files from the ENCODE portal at the UCSC Genome Browser.
T-KDE assumes all ChIP-seq peak files are in 3 column format (chromosome#, txStart, and txEnd) and there is a .nfo file that contains all unique cell line names. Examples can be found under ./input/Gabp folder.
T-KDE will produce a .bed file under a user-specified folder (i.e., ./output/Gabp). The final bed file is in 4 column format (chromosome#, txStart, txEnd, and number of cell lines that contain the site). Since T-KDE used the top of a bump as the predicated site, thus, txStart and txEnd are the same.


To format raw ChIP-seq files into 3 column format, go to ./script folder
   - run ./get3ColsChipSeq shell script


There are 2 ways to run the T-KDE software, 1) sequentially or 2) in parallel. Parallel processing may speedup the process.

1) Sequential execution: under matlab command line, run
matlab>> demo

2) Parallel execution: under matlab command line, run
matlab>> matlabpool open 12    //start 12 processors in matlab command line
matlab>> demo_par              //run T-KDE program
matlab>> matlabpool close      //end parallel processing             

Note: input and output parameters, path, etc. can be modified in the demo.m or demo_par.m file.


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Misc
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This software is put together by YuanYuan Li (yuanyuan.li@nih.gov). The @kde software is written by Dr. Alexander Ihler. The original KDE software package can be downloaded from http://www.ics.uci.edu/~ihler/code/index.html


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Contact
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Leping Li, Ph.D.
Tel (919) 541-5168 
Fax (919) 541-4311 
li3@niehs.nih.gov

