Table 1.

Overview of commonly used techniques for gene regulatory network mapping and their advantages and limitations

Method	Characteristics	Advantages	Limitations
Computational inference (reverse engineering)	Infers putative regulatory relationships from gene expression data	Fast; cheap	The interactions predicted could be indirect (they do not have to reflect physical interactions); regulators that themselves do not change in expression will be missed; detection limits of mRNA measurements will affect GRN predictions (regulators or genes expressed at low levels will be missed)
Chromatin immunoprecipitation (ChIP)	Experimentally identifies physical interactions between TFs and DNA; TF-centered (protein-to-DNA)	In vivo; can detect TF dimers and complexes	Condition-dependent interactions can be missed; needs high-quality, highly specific ChIP-grade antibodies; when a universal tag is used for immunoprecipitation, TF is usually overexpressed; peak calling required
Yeast one-hybrid (Y1H)	Experimentally identifies physical interactions between DNA and TFs; gene-centered (DNA-to-protein)	Heterologous; condition- and context-independent	TFs that require post-translational modifications before binding DNA will be missed; not yet suitable for heterodimers