Every assay has strengths and weaknesses, so it's a good idea to try more than one, if possible. ChIP-on-chip is significantly cheaper than ChIP-Seq, but unless you tile the entire genome, you will miss any region not represented on your chip. HELP probes only a fraction of the genome, but a genome's worth of testable HpaII fragments will fit on a single array, making analysis relatively inexpensive. (Greally now uses a 1.32-million element Nimblegen array.) You can use other assays (not described here) to double-check your results (see #2).
Generating data is not difficult, says Greally. "The challenge isn't the assay, it's what you do afterwards. People don't pay sufficient attention to validation," he says. As with gene-expression microarrays, it is wise to pick a subset of data points and check them using a completely separate method. Greally validated the HELP data in his PloS ONE study using Sequenom's EpiTyper ...
