Dissection of a complex transcriptional response using genome-wide transcriptional modelling.

Modern genomics technologies generate huge data sets creating a demand for systems level, experimentally verified, analysis techniques. We examined the transcriptional response to DNA damage in a human T cell line (MOLT4) using microarrays. By measuring both mRNA accumulation and degradation over a short time course, we were able to construct a mechanistic model of the transcriptional response.

Correction of scaling mismatches in oligonucleotide microarray data.

Background: Gene expression microarray data is notoriously subject to high signal variability. Moreover, unavoidable variation in the concentration of transcripts applied to microarrays may result in poor scaling of the summarized data which can hamper analytical interpretations. This is especially relevant in a systems biology context, where systematic biases in the signals of particular genes can have severe effects on subsequent analyses.

Ranked prediction of p53 targets using hidden variable dynamic modeling.

Full exploitation of microarray data requires hidden information that cannot be extracted using current analysis methodologies. We present a new approach, hidden variable dynamic modeling (HVDM), which derives the hidden profile of a transcription factor from time series microarray data, and generates a ranked list of predicted targets. We applied HVDM to the p53 network, validating predictions experimentally using small interfering RNA.