Table 1.

The comprehensive information of single-cell multimodal profiling methods

Multimodal	Method	Genome	Transcriptome	Epigenome	Proteome	Object	Physical separation before amplification	High-throughput	Metrics	Time	Journal	Reference
Transcriptome + genome	DR-seq	gDNA	mRNA	-	-	13 cells	No	No	CNVs; gene expression	2015	Nat Biotechnol	Dey et al.
	G&T-seq	gDNA	Full-length mRNA	-	-	~200 cells	Yes; oligo-dT-coated magnetic beads	No	Chromosomal aneuploidies; inter-chromosomal fusions; SNVs; chromosomal rearrangements; gene expression	2015	Nat Methods	Macaulay et al.
	SIDR-seq	gDNA	Total RNA (including non-coding RNA)	-	-	43 cells	Yes; hypotonic lysis and antibody-conjugated magnetic microbeads	No	Genomic variations; transcriptomic patterns	2018	Genome Res	Han et al.
	TARGET-seq	Target gDNA	mRNA; target mRNA	-	-	4559 cells	No	Yes	Known target somatic mutations; SNVs,small indels; gene expression	2019	Mol Cell	Rodriguez-Meira et al.
Transcriptome + genome +methylome	scTrio-seq	gDNA	Cytosolic mRNA	gDNA methylation	-	25 cells	Yes; centrifugation	No	CNVs; promoter and gene body methylation levels; gene expression	2016	Cell Res	Hou et al.
Transcriptome + methylome	scM&T-seq	-	Full-length mRNA	gDNA methylation	-	61 cells	Yes; oligo-dT-coated magnetic beads	Yes	DNA methylome data; transcriptome data	2016	Nat Methods	Angermueller et al.
	scMT-seq	-	Cytosolic mRNA	gDNA methylation	-	9 cells	Yes; micropipette	No	Methylome, SNPs and transcriptome data	2016	Genome Biol	Hu et al.
Transcriptome + chromatin accessibility	sci-CAR	-	Nuclear mRNA	chromatin accessibility	-	~10,000 nuclei	No	Yes	Chromatin accessibility and gene expression	2018	Science	Cao et al.
	scCAT-seq	-	Cytosolic mRNA	Chromatin accessibility	-	176 cells	Yes; mild lysis and physical dissociation	Yes		2019	Nat Commun	Liu et al.
	SNARE-seq	-	Nuclear mRNA	Chromatin accessibility	-	~10,000 nuclei	No	Yes		2019	Nat Biotechnol	Chen et al.
	SNARE-seq2	-	mRNA	Chromatin accessibility	-	>80,000 nuclei or cells	No	Yes		2021	Nat Protocols	Plongthongkum et al.
	Paired-seq	-	Nuclear mRNA	Chromatin accessibility	-	>10,000 nuclei	No	Yes		2019	Nat Struct Mol Biol	Zhu et al.
	SHARE-seq	-	mRNA	Chromatin accessibility	-	>10,000 cells or nuclei	No	Yes		2020	Cell	Ma et al.
	ISSAAC-seq	-	Nuclear mRNA	Chromatin accessibility	-	>10,000 nuclei	No	Yes		2022	Nat Methods	Xu et al.
Transcriptome + histone modification	EpiDamID	-	Total mRNA	Histone modification	-	2,943 cells	No	No	Histone modification and gene expression	2022	Mol Cell	Rang et al.
Genome + methylome	Methyl-HiC	gDNA	-	gDNA methylation	-	150 nuclei	No	No	General features of chromosomal architecture (chromatin loops, TADs); DNA methylome	2019	Nat Methods	Li et al.
	sn-m3C-seq	gDNA	-	gDNA methylation	-	~4200 nuclei	No	No	3D chromatin conformation; Cytosine DNA methylation	2019	Nat Methods	Lee et al.
	Single-cell COOL-seq	gDNA	-	gDNA methylation	-	24 nuclei	No	No	Chromatin state; nucleosome position; DNA methylation; CNVs and ploidy	2017	Cell Res	Guo et al.
Transcriptome + methylome + chromatin accessibility	scNMT-seq	-	Cytosolic mRNA	gDNA methylation; chromatin accessibility	-	70 cells	Yes; oligo-dT-coated magnetic beads	No	Chromatin accessibility, DNA methylation; transcriptome	2018	Nat Commun	Clark et al.
	scNOMeRe-seq	-	Cytosolic mRNA	gDNA methylation; chromatin accessibility	-	233 cells	Yes; oligo-dT-coated magnetic beads	No	Single-cell nucleosome occupancy; DNA methylome; RNA expression	2021	Nat Commun	Wang et al.
	scChaRM-seq	-	mRNA	gDNA methylation; chromatin accessibility	-	148 cells	Yes; oligo-dT-coated magnetic beads	No	DNA methylome, chromatin accessibility and transcriptome	2021	Cell Stem Cell	Yan et al.
Transcriptome + proteome	PEA/STA	-	Target mRNA	-	38 surface proteins	87 cells	No	No	Gene and protein expression	2016	Genome Biol	Genshaft et al.
	PLAYR	-	40 target mRNA	-	40 surface proteins	10,000 cells	No	Yes	Protein epitopes and multiple RNA	2016	Nat Methods	Frei et al.
	CITE-seq	-	mRNA	-	>100 surface proteins	8,005 cells	No	Yes	Protein epitopes and transcriptomes	2017	Nat Methods	Stoeckius et al.
	REAP-seq	-	mRNA	-	82 surface proteins	7,271 cells	No	Yes	Protein epitopes and transcriptomes	2017	Nat Biotechnol	Peterson et al.
	ECCITE-seq	-	mRNA, V(D)J regions,perturbation gsRNA	-	>100 surface proteins	5935 cells	No	Yes	Proteome, V(D)J regions, transcriptome, clonotype and CRISPR perturbation information	2019	Nat Methods	Mimitou et al.
	Perturb-CITE-seq	-	mRNA,perturbation gsRNA	-	20 surface proteins	~218,000 cells	No	Yes	Proteome, transcriptome and CRISPR perturbation information	2021	Nat Genet	Frangieh et al.
	RAID	-	mRNA	-	6 intracellular (phospho-) proteins	384 fixed cells	No	No	Gene and protein expression	2019	Sci Rep	Gerlach et al.
	QuRIE-seq	-	mRNA	-	80 intra- or extracellular (phospho)proteins	4,754 cells	No	Yes	Gene and protein expression	2021	Cell Rep Methods	Rivello et al.
	INs-seq	-	mRNA	-	Several intracellular proteins	5000 cells	No	Yes	Single-cell transcriptional, signaling, TF, and metabolism maps	2020	Cell	Katzenelenbogen et al.
	inCITE-seq	-	Nuclear mRNA	-	Several intra-nuclear protein	~10,000 nuclei	No	Yes	Transcription factors (TFs) and gene expression	2021	Nat Methods	Chung et al.
Epigenome + proteome	ICICLE-seq	-	-	Chromatin accessibility	46 surface proteins	>10,000 cells	No	Yes	Chromatin accessibility; protein levels	2021	Elife	Swanson et al.
Transcriptome + epigenome + proteome	TEA-seq	-	mRNA	Chromatin accessibility	46 surface proteins	>10,000 cells	No	Yes	Chromatin accessibility; protein levels; gene expression	2021	Elife	Swanson et al.
	NEAT-seq	-	mRNA	Chromatin accessibility	Several intra-nuclear protein	6000 cells	No	Yes	TF gene locus chromatin accessibility, RNA expression, protein abundance and genome-wide TF binding motif accessibility	2022	Nat Methods	Chen et al.
Genome + proteome	Tapestri	gDNA	-	-	45 surface proteins	~10,000 cells	No	Yes	SNV, CNV and protein levels	2022	Methods Mol Biol	Ruff et al.
Genome + epigenome + proteome	PHAGE-ATAC	mtDNA		Chromatin accessibility	Several intra- or extracellular proteins	8366 cells	No	Yes	Surface and intracellular proteins, chromatin accessibility and mtDNA	2021	Nat Biotechnol	Fiskin et al.
	ASAP-seq	mtDNA	-	Chromatin accessibility	>200 intra- or extracellular proteins	>10,000 cells	No	Yes	Chromatin accessibility; protein expression; somatic mtDNA mutations	2021	Nat Biotechnol	Mimitou et al.
Transcriptome + genome + epigenome + proteome	DOGMA-seq	mtDNA	mRNA	Chromatin accessibility	>200 intra- or extracellular proteins	>10,000 cells	No	Yes	Chromatin accessibility; gene and protein expression; somatic mtDNA mutations	2021	Nat Biotechnol	Mimitou et al.
Spatial transcriptome + proteome	DBiT-Seq	-	Spatial mRNA - 10μm	-	22 surface proteins	Pre-fixed tissue section	No	Yes	Spatial transcriptomics and proteins	2020	Cell	Liu et al.
	SM-Omics	-	Spatial mRNA - 100μm	-	multiplex proteins	Pre-fixed tissue section	No	Yes		2022	Nat Commun	Vickovic et al.
	CosMx SMI	-	Spatial mRNA - 10μm	-	64 surface proteins	Pre-fixed tissue section	No	No		2022	Blood	Gui et al.
	spatial CITE-seq	-	Spatial mRNA - 50μm	-	189 surface proteins	Pre-fixed tissue section	No	Yes		2022	Preprint	Liu et al.