Double error shrinkage method for identifying protein binding sites observed by tiling arrays with limited replication.
BACKGROUND
ChIP-chip has been widely used for various genome-wide biological investigations. Given the small number of replicates (typically two to three) per biological sample, methods of analysis that control the variance are desirable but in short supply. We propose a double error shrinkage (DES) method by using moving average statistics based on local-pooled error estimates which effectively control both heterogeneous error variances and correlation structures of an extremely large number of individual probes on tiling arrays.


RESULTS
Applying DES to ChIP-chip tiling array study for discovering genome-wide protein-binding sites, we identified 8400 target regions that include highly likely TFIID binding sites. About 33% of these were well matched with the known transcription starting sites on the DBTSS library, while many other newly identified sites have a high chance to be real binding sites based on a high positive predictive value of DES. We also showed the superior performance of DES compared with other commonly used methods for detecting actual protein binding sites.
Kim
Youngchul
Y
Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USA.
Bekiranov
Stefan
S
Lee
Jae K
JK
Park
Taesung
T
D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D004261:DNA Replication; D020869:Gene Expression Profiling / Q000379:methods*; D015894:Genome, Human; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods