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Bioinformatics Advance Access originally published online on July 26, 2005
Bioinformatics 2005 21(18):3629-3636; doi:10.1093/bioinformatics/bti593
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TileMap: create chromosomal map of tiling array hybridizations

Hongkai Ji 1 and Wing Hung Wong 2,*

1Department of Statistics, Harvard University Cambridge, MA 02138, USA
2Department of Statistics, Stanford University Stanford, CA 94305, USA

*To whom correspondence should be addressed.

Motivation: Tiling array is a new type of microarray that can be used to survey genomic transcriptional activities and transcription factor binding sites at high resolution. The goal of this paper is to develop effective statistical tools to identify genomic loci that show transcriptional or protein binding patterns of interest.

Results: A two-step approach is proposed and is implemented in TileMap. In the first step, a test-statistic is computed for each probe based on a hierarchical empirical Bayes model. In the second step, the test-statistics of probes within a genomic region are used to infer whether the region is of interest or not. Hierarchical empirical Bayes model shrinks variance estimates and increases sensitivity of the analysis. It allows complex multiple sample comparisons that are essential for the study of temporal and spatial patterns of hybridization across different experimental conditions. Neighboring probes are combined through a moving average method (MA) or a hidden Markov model (HMM). Unbalanced mixture subtraction is proposed to provide approximate estimates of false discovery rate for MA and model parameters for HMM.

Availability: TileMap is freely available at http://biogibbs.stanford.edu/~jihk/TileMap/index.htm

Contact: whwong{at}stanford.edu

Supplementary information: http://biogibbs.stanford.edu/~jihk/TileMap/index.htm (includes coloured versions of all figures)

Received on May 2, 2005; revised on July 19, 2005; accepted on July 20, 2005

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