Opportunities and tradeoffs in single-cell transcriptomic technologies

• Published in: Trends in genetics 2024-01, Vol.40 (1), p.83-93
• Main Authors: Conte, Matilde I., Fuentes-Trillo, Azahara, Conde, Cecilia Domínguez
• Format: Article
• Language: English
• Subjects: allele-specific expression; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Sequence Analysis, RNA; single-cell transcriptomics; transcript-level analysis; Transcriptome - genetics
• ISSN: 0168-9525
• DOI: 10.1016/j.tig.2023.10.003

•Different single-cell sequencing approaches have unique strengths and weaknesses, with cellular throughput and transcript coverage being generally anticorrelated•Characterization of rearranged V(D)J sequences in lymphocytes are a valuable complement to single-cell analysis of adaptive immune responses•Single-cell transcriptomics start to go beyond gene-level quantification and incorporate differential transcription start site and isoform usage in a cell state-specific manner•Long-read sequencing technologies is the next frontier in single-cell genomics at scale Recent technological and algorithmic advancements enable single-cell transcriptomic analysis with remarkable depth and breadth. Nonetheless, a persistent challenge is the compromise between the ability to profile high numbers of cells or achieving full-length transcript coverage. Currently, the field is progressing and developing new and creative solutions that improve cellular throughput, gene detection sensitivity and full-length transcript capture. Furthermore, long-read sequencing approaches of single cell transcripts are breaking frontiers that have previously blocked full transcriptome characterization. We here present a comprehensive overview of available options for single-cell transcriptome profiling, highlighting the key advantages and disadvantages of each approach. Recent technological and algorithmic advancements enable single-cell transcriptomic analysis with remarkable depth and breadth. Nonetheless, a persistent challenge is the compromise between the ability to profile high numbers of cells or achieving full-length transcript coverage. Currently, the field is progressing and developing new and creative solutions that improve cellular throughput, gene detection sensitivity and full-length transcript capture. Furthermore, long-read sequencing approaches of single cell transcripts are breaking frontiers that have previously blocked full transcriptome characterization. We here present a comprehensive overview of available options for single-cell transcriptome profiling, highlighting the key advantages and disadvantages of each approach.