DTW4Omics: Comparing Patterns in Biological Time Series

When studying time courses of biological measurements and comparing these to other measurements eg. gene expression and phenotypic endpoints, the analysis is complicated by the fact that although the associated elements may show the same patterns of behaviour, the changes do not occur simultaneously. In these cases standard correlation-based measures of similarity will fail to find significant associations. Dynamic time warping (DTW) is a technique which can be used in these situations to find the optimal match between two time courses, which may then be assessed for its significance. We implement DTW4Omics, a tool for performing DTW in R. This tool extends existing R scripts for DTW making them applicable for “omics” datasets where thousands entities may need to be compared with a range of markers and endpoints. It includes facilities to estimate the significance of the matches between the supplied data, and provides a set of plots to enable the user to easily visualise the output. We illustrate the utility of this approach using a dataset linking the exposure of the colon carcinoma Caco-2 cell line to oxidative stress by hydrogen peroxide (H2O2) and menadione across 9 timepoints and show that on average 85% of the genes found are not obtained from a standard correlation analysis between the genes and the measured phenotypic endpoints. We then show that when we analyse the genes identified by DTW4Omics as significantly associated with a marker for oxidative DNA damage (8-oxodG), through over-representation, an Oxidative Stress pathway is identified as the most over-represented pathway demonstrating that the genes found by DTW4Omics are biologically relevant. In contrast, when the positively correlated genes were similarly analysed, no pathways were found. The tool is implemented as an R Package and is available, along with a user guide from http://web.tgx.unimaas.nl/svn/public/dtw/.