RT Journal
A1 Johnson, David S.
A1 Li, Wei
A1 Gordon, D. Benjamin
A1 Bhattacharjee, Arindam
A1 Curry, Bo
A1 Ghosh, Jayati
A1 Brizuela, Leonardo
A1 Carroll, Jason S.
A1 Brown, Myles
A1 Flicek, Paul
A1 Koch, Christoph M.
A1 Dunham, Ian
A1 Bieda, Mark
A1 Xu, Xiaoqin
A1 Farnham, Peggy J.
A1 Kapranov, Philipp
A1 Nix, David A.
A1 Gingeras, Thomas R.
A1 Zhang, Xinmin
A1 Holster, Heather
A1 Jiang, Nan
A1 Green, Roland D.
A1 Song, Jun S.
A1 McCuine, Scott A.
A1 Anton, Elizabeth
A1 Nguyen, Loan
A1 Trinklein, Nathan D.
A1 Ye, Zhen
A1 Ching, Keith
A1 Hawkins, David
A1 Ren, Bing
A1 Scacheri, Peter C.
A1 Rozowsky, Joel
A1 Karpikov, Alexander
A1 Euskirchen, Ghia
A1 Weissman, Sherman
A1 Gerstein, Mark
A1 Snyder, Michael
A1 Yang, Annie
A1 Moqtaderi, Zarmik
A1 Hirsch, Heather
A1 Shulha, Hennady P.
A1 Fu, Yutao
A1 Weng, Zhiping
A1 Struhl, Kevin
A1 Myers, Richard M.
A1 Lieb, Jason D.
A1 Liu, X. Shirley
T1 Systematic evaluation of variability in ChIP-chip experiments using predefined DNA targets
JF Genome Research 
JO Genome Research 
YR 2008 
FD March 01 
VO 18 
IS 3 
SP 393 
OP 403 
DO 10.1101/gr.7080508 
UL http://genome.cshlp.org/content/18/3/393.abstract 
AB The most widely used method for detecting genome-wide protein–DNA interactions is chromatin immunoprecipitation on tiling microarrays, commonly known as ChIP-chip. Here, we conducted the first objective analysis of tiling array platforms, amplification procedures, and signal detection algorithms in a simulated ChIP-chip experiment. Mixtures of human genomic DNA and “spike-ins” comprised of nearly 100 human sequences at various concentrations were hybridized to four tiling array platforms by eight independent groups. Blind to the number of spike-ins, their locations, and the range of concentrations, each group made predictions of the spike-in locations. We found that microarray platform choice is not the primary determinant of overall performance. In fact, variation in performance between labs, protocols, and algorithms within the same array platform was greater than the variation in performance between array platforms. However, each array platform had unique performance characteristics that varied with tiling resolution and the number of replicates, which have implications for cost versus detection power. Long oligonucleotide arrays were slightly more sensitive at detecting very low enrichment. On all platforms, simple sequence repeats and genome redundancy tended to result in false positives. LM-PCR and WGA, the most popular sample amplification techniques, reproduced relative enrichment levels with high fidelity. Performance among signal detection algorithms was heavily dependent on array platform. The spike-in DNA samples and the data presented here provide a stable benchmark against which future ChIP platforms, protocol improvements, and analysis methods can be evaluated.