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. 2022 Mar 21;10:854317. doi: 10.3389/fcell.2022.854317

TABLE 1.

Summary of reviewed single-cell multiomics methods.

Method Molecular layers profiled Throughput (low/medium/high) Special features (compared to techniques from same category) Format References
Epigenome Genome Transcriptome
Chromatin accessibility Chromatin conformation DNAme CNVs/ploidy/microsatellites/mutation poly(A)+ RNA
scCAT-seq x x + ⇑ usable fragments well Liu et al. (2019)
Paired-seq x x +++ ⇑ throughput well Zhu et al. (2019)
sc(ATAC + RNA)-seq x x + ⇓ cost; simple workflow well Reyes et al. (2019a)
sci-CAR x x +++ ⇑ acc. & RNA intersect coverage well Cao et al. (2018)
SNARE-seq x x +++ ⇑ sensitivity droplet Chen et al. (2019)
ASTAR-seq x x ++ ⇓ price-performance ratio microfluidics Xing et al. (2020)
SHARE-seq x x +++ ⇑ throughput, performance well Ma Sai. et al. (2020)
ISSAAC-seq x x +++ ⇑ throughput, performance (esp. ATAC) well/droplet Xu et al. (2022)
scDam&T-seq x x + protein-DNA interactions information well Rooijers et al. (2019)
scNOMe-seq x x + estimates nucleosome phasing well Pott, (2017)
scCOOL-seq x x x + ⇑ acc. & DNAme intersect coverage well Guo et al. (2017)
iscCOOL-seq x x ++ ⇑ accessibility coverage well Gu et al. (2019a)
scMethyl-HiC x x + ⇑ mapping rate well Li et al. (2019)
sn-m3C-seq x x +++ ⇑ DNAme coverage well Lee et al. (2019)
scNMT-seq x x x ++ ⇑ throughput well Clark et al. (2018)
scNOMeRe-seq x x x + ⇑ DNAme coverage well Wang et al. (2021)
scSIDR-seq x x + captures total RNA well Han et al. (2018)
TARGET-seq x x +++ ⇓ cost; ⇑ throughput well Rodriguez-Meira et al. (2019)
RETrace x x + captures microsatellites well Wei and Zhang, (2020)
scTrio-seq2 x x x ++ ⇑ DNAme coverage well Bian et al. (2018)

Throughput: + <500 cells, ++ <2000 cells, +++ >2000 cells. acc. = (chromatin) accessibility. scCAT-seq, single-cell chromatin accessibility and transcriptome sequencing), Paired-seq - parallel analysis of individual cells for RNA, expression and DNA, accessibility by sequencing, sc(ATAC + RNA)-seq - simultaneous chromatin accessibility and gene expression profiling, sci-CAR, single-cell combinatorial indexing-based chromatin accessibility and RNA, SNARE-seq, single-nucleus chromatin accessibility and mRNA, expression profiling; ASTAR-seq, assay for single-cell transcriptome and accessibility regions; SHARE-seq, simultaneous high-throughput ATAC, and RNA, expression with sequencing in single cells; ISSAAC-seq, in situ SHERRY, after ATAC-seq, scDam&T-seq - single-cell DNA, adenine methyltransferase identification (DamID) and messenger RNA, sequencing, scNOMe-seq - single-cell nucleosome occupancy and methylome-sequencing, scCOOL-seq, single-cell chromatin overall omic-scale landscape sequencing, iscCOOL-seq, improved single-cell chromatin overall omic-scale landscape sequencing; scMethyl-HiC, single-cell DNA, methylation and chromatin conformation capture, sn-m3C-seq - single-nucleus methyl-chromatin conformation capture sequencing, scNMT-seq, single-cell nucleosome, methylation and transcription sequencing, scNOMeRe-seq - single-cell nucleosome occupancy, methylome and RNA, expression sequencing; scSIDR-seq, simultaneous isolation and sequencing of genomic DNA, and total RNA, TARGET-seq, single-cell targeted mutational analysis and parallel RNA, sequencing, RETrace - simultaneous retrospective lineage tracing and methylation profiling of single cells, scTrio-seq - single-cell triple omics sequencing.