MAY 11, 2016 01:30 PM PDT

Microfluidic Single Cell Exome-seq and RNA-seq analysis of Tumor Composition

  • Head of Genome Sciences, McGill University and Genome Quebec Innovation Centre (MUGQIC), Associate Professor, Human Genetics, Department of Bioengineering
      Ioannis (Jiannis) Ragoussis studied Biochemistry at the University of Tuebingen, Germany, where he obtained his PhD. He did his postdoctoral studies as EMBO fellow with J. Trowsdale at the Imperial Cancer Research Fund Laboratories in London, UK. Subsequently he became lecturer and then senior lecturer at the division of Medical and Molecular Genetics at Guy's Hospital, then Guy's and now King's Medical School. In 2001 he moved to the University of Oxford as Head of Genomics and in 2013 to McGill University where he is Head of Genome Sciences at the McGill University and Genome Quebec Innovation Centre (MUGQIC) and Associate Professor in Human Genetics and at the Department of Bioengineering. He is also affiliated Professor at the Biomedical Sciences research Centre A. Fleming in Greece and the King Abdulaziz University. He has developed expertise in all fields of genomics and functional genomics. His main interest is on developing NGS based approaches to disease gene identification, as well as functional genomics approaches for the identification of prognostic markers and associated pathways in breast cancer.

      He is responsible for the Genomic Platform Development within the MUGQIC Genome Canada Genome Innovation Node and Canada's Genomics Enterprize funded by CFI. He chairs the internal management committee of MUGQIC, oversees genomic platform operation and new technology evaluation and integration. His Lab works on Technical Developments including the Single Cell Genomics Lab of MUGQIC and Mutation Detection Technologies with focus on the genomic and transcriptomic analysis of single cells. Supported by CF the lab includes a Fluidigm BioMark HD instrument and two Fluidigm C1 instruments, as well as an Oxford Nanopore MinION device. Both single cell whole genome expression profiling as well as whole exome protocols are validated and available for external users.


    Human breast tumors have been shown to exhibit extensive inter- and intra-tumor heterogeneity. While recent advances in genomic technologies have allowed us to deconvolute this heterogeneity, few studies have addressed the functional consequences of diversity within tumor populations. We performed single cell RNA and exome sequencing of treatment resistant breast tumor derived xenografts (PDX) to identify population structure. Genes differentially expressed between these subpopulations are involved in proliferation and differentiation. Microfluidic whole genome amplification followed by whole exome capture of single cells, identified driver mutations as well as a number of sub-clonal mutations that are being investigated further. Loss of heterozygocity was observed in 16 TCGA cancer driver genes and novel mutations in 7 known cancer driver genes. Careful comparison of the exome sequencing data allowed the association of driver gene mutation prevalence with tumor progression. These findings are important in our understanding the functional consequences of intra-tumor heterogeneity with respect to clinically important phenotypes such as invasion, metastasis and drug-resistance.

    Learning Objectives:

    • Develop an understanding of the technology behind single cell genomics 
    • Understand the data analysis and quality control processes for single cell data
    • Understand single cell expression profiling approaches using high throughput quantitative PCR
    • Understand the relevance of single cell genomics in the development of personalized medicine approaches

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