The long road to long reads - exploring alternative splicing in single cells

The long road to long reads - exploring alternative splicing in single cells

Dr Iain Macaulay; Earlham Institute

Dr. Iain Macaulay is a group leader in technical development at the Earlham Institute, focussing the application of single-cell technologies in a number of biological areas of interest, ranging from microbial communities to human tissues and even forensic science. He also leads EI’s Single-cell and Spatial Analysis Platform which enables researchers from across the UK to access our advanced technology platform to undertake their own research. A major interest of his research has been technical development for single-cell analysis, with a view to recovering as much information as possible from individual cells - in particular his group has been exploring long read sequencing approaches and their applicability to single (or rare) cells to investigate how alternative splicing can contribute to concepts like cell type and cell identity.

Long-read sequencing technologies have enormous potential to transform our understanding of alternative splicing across diverse biological systems. When applied to cDNA or RNA, they offer the possibility of resolving full-length isoforms and complex transcript structures that are difficult to capture using conventional short-read approaches. But can these technologies be successfully applied at the level of individual cells? And if so, how might they help us explore blood cell development and immune cell biology more broadly? These questions have been a focus of our lab for over a decade. In this talk, I will outline the progress we have made, the technical and analytical challenges that remain, and the lessons learned along the way. I will focus particularly on mouse haematopoietic development, as well as emerging opportunities for long-read analysis of T- and B-cell receptor sequences at single-cell resolution.

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