UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing

The use of single-cell combinatorial indexing sequencing via droplet microfluidics presents an attractive approach for balancing cost, scalability, robustness and accessibility. However, existing methods often require tailored protocols for individual modalities, limiting their automation potential and clinical applicability. To address this, we introduce UDA-seq, a universal workflow that integrates a post-indexing step to enhance throughput and systematically adapt existing droplet-based single-cell multimodal methods. UDA-seq was benchmarked across various tissue and cell types, enabling several common multimodal analyses, including single-cell co-assay of RNA and VDJ, RNA and chromatin, and RNA and CRISPR…

• NN
  National Natural Science Foundation of China

  Awards: 92168201, 32121001, 92149301, 31970760, 82488301, 92374104, 81921006, 32341001, YSBR-012, 32100479, 82330044, 82361148131
• CA
  Chinese Academy of Sciences

  Awards: YSBR-012, XDB38020500, YSBR-076
• PU
  Peking Union Medical College Hospital
• NK
  National Key Research and Development Program of China

  Awards: 2023YFC3402703, 2022YFA1103700, 2019YFA0801702, 2020YFA0804000