Characterization of full-length isoforms in single cells with FLT-seq and FLAMES
About Matthew Ritchie
Associate Professor Matthew Ritchie is a Laboratory Head in the Epigenetics and Development Division at WEHI in Melbourne, Australia. He is an experienced computational researcher, with skills in analysing high-throughput sequencing data and developing open-source software for bioinformatics analysis. Through close collaboration with bench scientists, his analyses have revealed new insights into epigenetic processes, hematopoiesis, and apoptosis that have been published in leading journals including Cell, Cancer Cell and Genome Biology.
Alternative splicing shapes the phenotype of cells in development and disease. Long-read RNA-sequencing recovers full-length transcripts but has limited throughput for single-cell analysis. We developed single-cell full-length transcript sequencing by sampling (FLT-seq), together with the computational pipeline FLAMES to overcome these issues and perform isoform discovery and quantification, splicing analysis, and mutation detection in single cells. With FLT-seq and FLAMES, we performed comprehensive characterization of the full-length isoforms in single cells of different types and species and identified thousands of unannotated isoforms, alternative transcript usage in different cell populations, and linked mutations known to confer drug resistance to transcriptome heterogeneity.