RT Journal Article SR Electronic T1 Comprehensive Benchmarking of CITE-seq versus DOGMA-seq Single Cell Multimodal Omics JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.12.15.472792 DO 10.1101/2021.12.15.472792 A1 Xu, Zhongli A1 Heidrich-O’Hare, Elisa A1 Chen, Wei A1 Duerr, Richard H. YR 2021 UL http://biorxiv.org/content/early/2021/12/16/2021.12.15.472792.abstract AB The recently developed transcription, epitopes, and chromatin accessibility by sequencing (TEA-seq) and similar DOGMA-seq single-cell trimodal omics assays provide unprecedented opportunities for understanding cell biology, but independent optimization, benchmarking and evaluation are lacking. We explored the utility, pros and cons of DOGMA-seq compared to the bimodal cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) assay in activated and stimulated human peripheral blood T cells. We identified an optimal incubation time and concentration of digitonin (DIG) for cell permeabilization and found that single-cell trimodal omics measurements after DIG permeabilization were generally better than after an alternative “low-loss lysis” (LLL) permeabilization condition. Next, we found that DOGMA-seq with optimized DIG permeabilization and its ATAC library provides more information, even though its mRNA and cell surface protein antibody-derived tag (ADT) libraries have slightly inferior quality, compared to CITE-seq. Finally, we recognized the additional value of DOGMA-seq for studying lineage-specific T helper cells.Competing Interest StatementThe authors have declared no competing interest.