- Vallejo, Jenifer;
- Saigusa, Ryosuke;
- Gulati, Rishab;
- Armstrong Suthahar, Sujit Silas;
- Suryawanshi, Vasantika;
- Alimadadi, Ahmad;
- Durant, Christopher P;
- Ghosheh, Yanal;
- Roy, Payel;
- Ehinger, Erik;
- Pattarabanjird, Tanyaporn;
- Hanna, David B;
- Landay, Alan L;
- Tracy, Russell P;
- Lazar, Jason M;
- Mack, Wendy J;
- Weber, Kathleen M;
- Adimora, Adaora A;
- Hodis, Howard N;
- Tien, Phyllis C;
- Ofotokun, Igho;
- Heath, Sonya L;
- Shemesh, Avishai;
- McNamara, Coleen A;
- Lanier, Lewis L;
- Hedrick, Catherine C;
- Kaplan, Robert C;
- Ley, Klaus
Background
Cryopreserved peripheral blood mononuclear cells (PBMCs) are frequently collected and provide disease- and treatment-relevant data in clinical studies. Here, we developed combined protein (40 antibodies) and transcript single-cell (sc)RNA sequencing (scRNA-seq) in PBMCs.Results
Among 31 participants in the Women's Interagency HIV Study (WIHS), we sequenced 41,611 cells. Using Boolean gating followed by Seurat UMAPs (tool for visualizing high-dimensional data) and Louvain clustering, we identified 50 subsets among CD4+ T, CD8+ T, B, NK cells, and monocytes. This resolution was superior to flow cytometry, mass cytometry, or scRNA-seq without antibodies. Combined protein and transcript scRNA-seq allowed for the assessment of disease-related changes in transcriptomes and cell type proportions. As a proof-of-concept, we showed such differences between healthy and matched individuals living with HIV with and without cardiovascular disease.Conclusions
In conclusion, combined protein and transcript scRNA sequencing is a suitable and powerful method for clinical investigations using PBMCs.