Judith and David Coffey Seminar Series: Eduardo Eyras

Title: Characterising the (epi)transcriptome at single-molecule resolution with
long-read sequencing 

Speaker: Professor Eduardo Eyras (ANU) 

Abstract: We describe our recent developments in the study of transcriptomes and
epitranscriptomes using long-read sequencing.  The epitranscriptome embodies many
largely unexplored functions of RNA.  A major roadblock in epitranscriptomics is the
lack of transcriptome-wide methods that detect multiple RNA modifications, identify RNA
modifications in individual molecules, and estimate modification stoichiometry
accurately.  We addressed these issues with CHEUI, a new method that processes signals
from nanopore direct RNA sequencing to identify RNA modifications at single molecule
resolution from any sample.  CHEUI outperforms other methods in detecting m6A and m5C
sites and quantifying their stoichiometry, and further reveals a non-random
co-occurrence of m6A and m5C in mRNA transcripts in cell lines and tissues.  We also
describe RISER, a method to perform in-silico biochemical-free enrichment or depletion
of RNA classes in real time during direct RNA sequencing.  RISER identifies RNA classes
directly from the first few seconds of the signal without needing basecalling or a
reference and communicates with the sequencing hardware in real-time to enact
biochemical-free targeted RNA sequencing.  We illustrate RISER for the enrichment and
depletion of coding and non-coding RNA, demonstrating a 3.4-3.6x enrichment and 6.2-6.7x
depletion of non-coding RNA in live sequencing experiments.  RISER and CHEUI unlock
novel ways to study transcriptomes and epitranscriptomes and enable discoveries and new
applications across multiple fields.  

About the speaker: Eduardo Eyras is an EMBL Australia Group Leader and Professor at the
Australian National University (ANU), where he develops computational methods to study
transcriptome and epitranscriptomes and their alterations in cancer using long-read
sequencing technologies.  Before joining ANU, Eduardo Eyras worked at the Sanger
Institute (2001-2004) and was group leader at the Pompeu Fabra University in Barcelona,
Spain (2005-2019).  During this time, he developed methods to annotate RNA alternative
splicing in genomes, contributed to the landmark analyses of the human, mouse, rat,
chicken, and cow genomes, and led a research program on Machine Learning applied to RNA
biology and cancer.