OCT 11, 2017 12:00 PM PDT

Examining Cancer with the minION: Methylation and Structural Variation

Speakers
  • Assistant Professor Department of Biomedical Engineering Johns Hopkins University
    Biography
      Winston Timp is an assistant professor in Biomedical Engineering at Johns Hopkins University. He earned bachelor degrees in Biochemistry, Chemistry, Physics and Electrical Engineering from the University of Illinois at Urbana. He then earned his a masters and PhD in Electrical Engineering from MIT, working at the Whitehead Institute in Paul Matsudaira's lab, focusing his thesis work on the study of cellular communication in a 3D microenvironment. After receiving his doctorate, he trained as a postdoc at Johns Hopkins in the labs of Andrew Feinberg and Andre Levchenko, studying the epigenetics of cancer.

      My lab's focus is in the development and application of sequencing technologies to gain a deeper understanding of biology and a more accurate set of clinical tools for human disease. We integrate biophysics, molecular biology and computational biology to create new tools for exploring the epigenome and genome. Leveraging these tools, we then explore interesting questions about fundamental biological concepts using model systems. We apply our newfound knowledge and toolset to clinical samples for diagnosis, surveillance and treatment of human disease. Recent projects range from diagnosis of infectious disease using nanopore sequencing, to developing new tools to characterize the genome and epigenome of cancer, to reading the transcriptome of the hummingbird.

    Abstract:

    Nanopore sequencing has enormous potential for application to cancer, but specifically offers advantages into two main arenas, epigenetics and structural variation. Methylation is well-known to be altered in cancer as compared to normal tissue, but how these changes arise and what patterns they are comprised of is only recently being explored. We have demonstrated the ability to sequencing phased methylation patterns in cancer versus normal samples over >5kb fragments, illustrating the potential of this technique.  Using methylation calling, we can probe the heterogeneous nature of the cancer epigenome, as well as the changes which occur between normal and cancer samples.  

    Structural variants comprise a significant fraction of mutations in cancer, e.g. 50% of pancreatic cancer mutations.  Unfortunately, limitations of conventional, short-read DNA sequencing technologies make it difficult to detect these variations which often lie in repetitive regions. Nanopore sequencing can overcome these limitations, allowing more in-depth study of SVs and phased SNVs. We applied solution-phase hybridization capture to target SV hotspots in pancreatic cancer samples with long-read sequencing.  We also demonstrate that with signal level analysis, we can call SNPs and SVs in the same sample.


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