2 research outputs found
Integrative analysis of ChIP-chip datasets in Saccharomyces cerevisiae
ChIP-chip is a technology originally developed to determine the binding sites
of proteins in chromatin on a genome wide scale. Its uses have since been
expanded to analyse other genome features, such as epigenetic modifications
and, in our laboratory, DNA damage. Datasets comprise many thousands of
data points and therefore require bioinformatic tools for their analysis. Currently
available tools are limited in their applications and lack the ability to
normalise data so as to allow relative comparisons between different datasets.
This has limited the analyses of multiple ChIP-chip datasets from different
experimental conditions.
The first part of the study presented here is bioinformatic, presenting a
selection of tools written in R for ChIP-chip data analysis, including a novel
normalisation procedure which allows datasets from different conditions to be
analysed together, permitting comparisons of values between different experiments
and opening up a new dimension of analysis of these datasets. A novel
enrichment detection procedure is presented, suited to many formats of data,
including protein binding (which forms peaks) and epigenetic modifications
(which can form extended regions of enrichment). Graphical tools are also
presented, to facilitate the analysis of these large datasets. A method of predicting
the output of a ChIP-chip dataset is presented, which has been used
to show that ChIP-chip is capable of detecting sequence dependent damage
events. All functions work together, using a common data format, and are
effcient and easy to use.
The second part of this study applies these bioinformatic tools in a biological
context. An analysis of Abf1 protein binding datasets has been
undertaken, revealing many more binding sites than had previously been
identified. Analysis of the sequences at these binding sites identifed the previously
determined consensus binding motif in only a subset, with no novel
motif identifiable in the remainder, suggesting binding may be in
uenced by
factors other than sequence