Research Project 6

Long-read single-cell and spatial transcriptomics to explore the diversity of isoform expression

About the Project

French National Centre for Scientific Research

Paris, France

Eamon McAndrew

Early Stage Researcher

Pascal Barbry

Main Supervisor

Université Cote’dAzur

PhD enrolment

Research Objectives

Analysis of isoform expression in single cells contributes to the study of cell states and disease states. We have previously developed methods for sc-lrRNA-seq with Nanopore. However, a complete analysis framework is missing. Our objectives are:

  • Develop new wet-lab protocols for the quantification of scRNA-seq data using exclusively Nanopore sequencing.
  • Develop an end-to-end pipeline for quantification and differential expression analysis or single cell data.
  • Develop new Artificial Intelligence methods functional characterization of isoforms derived from mis-splicing events.

 

Envisioned Secondments

  • Nanopore (Aino Järvelin): Collaboration in isoform quantification using Nanopre data.
  • WCM (Hagen Tilgner): Compare methods to Pacbio lr-scRNA-seq methods.

Early Stage Researcher

Eamon McAndrew

French National Centre for Scientific Research,
France

Originally from Ireland, I am now undertaking my doctorate studies as part of the LongTREC consortium at the Institute of Pharmacology Molecular and Cellular (IPMC) in Sophia Antipolis, Nice. I hold a Bachelor’s in Industrial Biochemistry from the University of Limerick and a Master’s in Biomedical Genomics from the University of Galway. During previous research assistant roles at the University of Galway, I applied deep learning to COVID-19 medical image analysis and explored applications in scRNA-seq data. At IPMC, my project utilizes sequencing data from Oxford Nanopore technologies to interpret single-cell isoform heterogeneity, delving into complex transcriptomic events beyond the reach of conventional short-read sequencing.

The project objectives include refining quantification and differential analysis methods to better understand the role of alternative splicing on cellular functions. Simultaneously, we seek to use artificial intelligence to methodically characterize the resulting isoforms, exploring the vast, intricate mechanisms that regulate the production of messenger RNAs within single cells. As a member of LongTREC’s network of forward-thinking scientists, I aim to push the boundaries of long-read RNA sequencing (lrRNA-seq) technology and drive a paradigm shift in our genomic comprehension and computational biology techniques.

About the Main Supervisor and Host Group

Pascal Barbry

French National Centre for Scientific Research,
France

Pascal Barbry’s group was created in 1999 to develop approaches in high throughput nucleic acid sequencing and functional genomics. Its central activity deals with high throughput sequencing, with a specialization in single-cell genomics since 2015. It is involved since 2018 in the consortium Human Cell Atlas, with the aim to generate an atlas of the different cell types populating the human body. Its work at forefront of the development in single-cell genomics since 2015 is illustrated today by the first installation in France in October 2022 of the Merscope™, Vizgen (3 rd instrument in Europe). This machine will be at the center of our development in spatial transcriptomics.