Table 1.

Summary of experimental methods to identify non-coding functional variants.

	Method	Throughput	Detection	Cell- and tissue-specific	Experiment	Ref
CRE-interactome	PCHi-C	High	Promoter-CRE interactome, target gene	Yes	In vivo (cell line)	[103,104]
	ECHi-C	High	Enhancer-CRE interactome	Yes	In vivo (cell line)	[106]
	HiChIP	High	Cell-type CRE interactome	Yes	In vivo (cell line)	[101]
TF–DNA binding	BET-seq	High	Binding free energy	No	In vitro	[43]
	STAMMP	High	Binding affinity	No	In vitro	[44]
	HiP-FA	High	Binding affinity and specificity	No	In vitro	[45]
	CASCADE	High	Cofactor recruitment by TFs	Yes	In vivo (cell line)	[46]
	SNP-SELEX	High	Binding affinity	No	In vitro	[47]
Gene expression	Luciferase reporter assay	Low	Bioluminescence	Yes	In vivo (cell line)	[82]
	MPRA	High	RNA-seq/flow cytometry	Yes	In vivo (cell line)	[86]
	STARR-seq	High	RNA-seq	Yes	In vitro (cell)	[88]
	enSERT	High	lacZ staining	Yes	In vivo	[89]
Post-transcriptional regulation	Luciferase reporter assay	Low	Bioluminescence	No	In vivo	[116]
		Low	Bioluminescence	No	In vitro	[113]
	Minigene splicing assays	Low	RNA-seq	No	In vitro (from patients)	[114]
	Patient iPSC WGS	High	RNA-seq	Yes	In vivo	[115]
	MPRAu	High	RNA-seq	Yes	In vitro (cells)	[118]
	Plumage	High	RNA-seq and bioluminescence	Yes	In vitro	[117]

PCHi-C, promoter-capture Hi-C; ECHi-C, enhancer-capture Hi-C; HiChIP, Hi-C library preparation followed by chromatin immunoprecipitation; BET-seq, Binding Energy Topography by sequencing; STAMMP, simultaneous transcription factor affinity measurements via microfluidic protein arrays; HiP-FA, high-performance fluorescence anisotropy; CASCADE, Customizable Approach to Survey Complex Assembly at DNA Elements; MPRA, massively parallel reporter assays; STARR-seq, self-transcribing active regulatory region sequencing; iPSC, induced pluripotent stem cell; WGS, whole-genome sequencing; MPRAu, Massively Parallel Reporter Assay for 3′ UTR.