TARGET-seq: novel method for single-cell mutational analysis and parallel RNA-sequencing [validation in cell lines; Figure 2 and Figure S3]

We developed TARGET-seq, a single-cell genotyping and RNA-seq method, which allows accurate detection of multiple mutations within single-cells from genomic and coding DNA in parallel with whole transcriptome analysis, providing a powerful tool to link transcriptional and genetic tumor heterogeneity. Single cell whole transcriptome analysis of JURKAT, SET2 and HSPCs using SMART-seq+, mRNA targeting (tSMARTseq) or TARGET-seq reveals very good correlations between methods. Overall design: Whole transcriptome analysis of single cells processed using SMART-seq+, mRNA targeting and TARGET-seq methods. We analyzed sequencing metrics, library quality and potential biases using TARGET-seq as compared to SMART-seq+ or mRNA targeting methods (tSMARTseq), in two different human cell lines (JURKAT and SET2) and primary HSPCs (Hematopoietic Stem and Progenitor Cells).