Open Access
Review
Table 1
Methods for single-cell multimodal Omicsa)
| Methods | Modalities assayed | Strategies for identifying modalities | Throughput | Engineering characteristics | PMID |
| scG&T-seq | DNA + RNA | I + II | Benchmarking: 130 cells Case study: 7 embryos, 41 iPSCs, HCC38-BL cells (n = 36) and single HCC38 cells (n = 32) |
Manually selected or flow cytometry | 25915121 |
| DR-seq | DNA + RNA | III + V | Benchmarking: 13 E14 cells, Case study: 21 SK-BR-3 cells | Mouth pipetting | 25599178 |
| TARGET-seq | DNA + RNA | III | Benchmarking: 180 single cells (JURKAT, n = 56; SET2, n = 86; and HSPC, n = 38) Case study: 458 HSPCs from 5 MPN patients; 2798 cells from a cohort of 8 patients with MF |
Fluorescent activated cell sorting | 30765193 |
| SIDR | DNA + RNA | II + III | Benchmarking: 43 cells | Sorting 1 μL of cell suspension (1 cell / uL) into each well of 48-well microplate | 29208629 |
| scM&T-seq | DNA methylation + RNA | I + II | Benchmarking & Case study: 76 individual serum ESCs and 16 ESCs grown in “2i” media | FACS after staining | 27150361 |
| scMT-seq | DNA methylation + RNA | I | Benchmarking & Case study: 15 sensory neurons from DRG | Micro-capillary pipetting | 30498128 |
| scTrio-seq | DNA methylation + RNA | II | Benchmarking: 6 HepG2 + 6 mESCs Case study: 26 hepatocellular carcinoma cells |
Mouth pipetting | 26902283 |
| scTrio-seq2 | DNA methylation + RNA | II | Case study: ~1900 cells from 12 CRC patients | Mouth pipetting | 33958790 |
| CoTECH | Protein–DNA interactions + RNA | III | Benchmarking: 1:1 mixed HEK293T and NIH 3T3 cells Case study: 6993 mESCs, 512 AGM cells + 736 YS cells |
Two rounds of combinatorial indexing | 33958790 |
| Paired-Tag | Protein–DNA interactions + RNA | II + III | Benchmarking: tens of thousands of HeLa cells Case study: ~70,000 nuclei from brain cells |
Four rounds of combinatorial indexing | 33589836 |
| scDam&T-seq | Protein–DNA interactions + RNA | II | – | FACS | 32350457 |
| sciCAR | Chromatin accessibility + RNA | III | Benchmarking: 4825 A549 cells after DEX treatment Case study: 11,296 cells from whole mouse kidneys |
Two rounds of combinatorial indexing | 30166440 |
| scCAT-seq | Chromatin accessibility + RNA | I | Benchmarking: 176 K562 cells, Hela-S3 and HCT116 Case study: 110 clinically discarded human embryos |
Two rounds of combinatorial indexing | 30692544 |
| SNARE-seq | Chromatin accessibility + RNA | IV | Benchmarking: 1047 cells from mixtures of BJ, H1, K562 and GM12878 Case study: 5081 cells from mouse neonatal cerebral cortex, 10,309 cells from adult mouse cerebral cortex |
FACS | 31611697 |
| SHARE-seq | Chromatin accessibility + RNA | II | Benchmarking: ~900 GM12878 + ~1300 NIH 3T3 Case study: 34,774 mouse skin cells, 23,278 GM12878 cells |
Three rounds of combinatorial indexing | 33098772 |
| Paired-seq | Chromatin accessibility + RNA | II + III | Benchmarking: ~2053 nuclei from mixture of NIH3T3, HepG2, HEK293T Case study: 15,191 nuclei from adult mouse cerebral cortex |
Five rounds of combinatorial indexing | 31695190 |
| ISSAAC-seq | Chromatin accessibility + RNA | III | Benchmarking: mixture of 293T and 3T3 (plate-based), PBMCs and K562 (droplet-based) Case study: 10,378 adult mouse cerebral cortex |
FACS or 10x Genomics scATAC platform | 36109677 |
| scNOMe-seq | DNA methylation + Nucleosome occupancy |
IV | Benchmarking & Case study: 19 GM12878 cells and 11 K562 cells | FACS | 28653622 |
| scCOOL-seq | DNA methylation + Nucleosome occupancy |
IV | Benchmarking: 24 mESCs Case study: 233 cells from mouse preimplantation embryos |
Mouth pipetting | 28621329 |
| scNMT-seq | DNA methylation + Nucleosome occupancy |
II + IV | Benchmarking: 70 mESCs Case study: 43 ES cells that were removed from LIF for 3 days |
FACS | 29472610 |
| snmCAT-seq | DNA methylation + Nucleosome occupancy |
IV + V | Benchmarking: mixture of H1 and HEK293T Case study: 4358 nuclei from postmortem human frontal cortex tissue, |
FACS | 35419551 |
| scNoMeRe-seq | DNA methylation + Nucleosome occupancy |
II + IV | Benchmarking & Case study: 233 mouse preimplantation embryos from different stages | FACS | 33623021 |
| CITE-seq | Cell surface protein + RNA | IV | Benchmarking: mixture of HeLa and 4T1 Case study: 8005 CBMCs |
10x Single Cell 3′ v1 or v2 | 28759029 |
| TEA-seq | RNA + Cell surface protein + Chromatin accessibility |
IV | Benchmarking & Case study: thousands of PBMCs | 10x Genomics scATAC platform | 33835024 |
| mtscATAC-seq | Chromatin accessibility + mtDNA | – | Benchmarking: mixture of GM11906 and TF1 Case study: 818 GM11906 cells from MERRF patient |
10x Genomics scATAC platform | 34083792 |
| ASAP-seq | Chromatin accessibility + Cell surface protein + mtDNA |
IV | Benchmarking: mixture of 293T and 3T3, PBMCs Case study: 10,928 cells from bone marrow, 8535 PBMCs after T cell stimulation |
10x Genomics Multiome kit | 34083792 |
| DOGMA-seq | Chromatin accessibility + RNA + Cell surface protein + mtDNA |
IV | Benchmarking: 6139 PBMCs after T cell stimulation | 10x Genomics Multiome kit | 34083792 |
| NEAT-seq | Chromatin accessibility + RNA + Nuclear protein |
IV | Benchmarking: mixture of K562 and mESCs Case study: human CD4 memory T cells |
10x Genomics Multiome kit | 35501385 |
| Perturb-seq | DNA perturbation + RNA | – | Benchmarking & Case study: 6 experiments analyzing 200,000 cells (BMDCs and K562) | 10x Chromium System | 27984732 |
| CROP-seq | DNA perturbation + RNA | – | Benchmarking : mixture of 3 KO cell lines of 293T Case study: 5798 Jurkat cells (screen of T-cell receptor activation) |
FACS | 28099430 |
| CRISP-seq | DNA perturbation + RNA | – | Benchmarking: bone marrow cells from mice Case study: 731 + 1186 + 6749 mice myeloid cells |
FACS | 27984734 |
| Methy-HiC | DNA methylation + Chromatin conformation |
– | Case study: 103 serum mESCs cultured in LIF and 47 2i mESCs cultured in LIF | FACS | 31384045 |
| Perturb-ATAC | DNA perturbation + Chromatin accessibility |
– | Benchmarking & Case study: 63 genotypes using ~4300 single cells | FACS | 30580963 |
| Spear-ATAC | DNA perturbation + Chromatin accessibility | – | Benchmarking: 3045 K562 cells Case study: 32,832 K562 cells representing 128 sgRNA genotypes |
10x Genomics scATAC platform | 34016988 |
| CRISPR-sciATAC | DNA perturbation + Chromatin accessibility | – | Benchmarking: 1986 cells from mixture of NIH3T3 and HEK293 Case study: 11,104 + 16,676 K562 cells (screening of chromatin modifier and chromatin remodeling complexes) |
Two rounds of combinatorial indexing | 33927415 |
a)
The summary for single-cell experimental strategies and throughput (represented by cells profiled in the indicated studies) of single-cell technologies as in Figure 3. MPN, myeloproliferative neoplasms. MF, myelofibrosis. DRG, dorsal root ganglion. CRC, colorectal cancer. DEX, dexamethasone. MERRF, myoclonic epilepsy with red ragged fibers. KO, knock out. LIF, leukemia inhibitory factor. I, physical separation. II, biochemical separation. III, split. IV, Conversion. V, computational deconvolution.
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