NOV 12, 2019 10:00 AM PST

Leveraging single cell copy number to resolve tumor clonality

SPONSORED BY: 10x Genomics, Inc.
C.E. CREDITS: P.A.C.E. CE | Florida CE
  • Professor of Translational Genomics; Co-Director, Institute of Translational Genomics Keck School of Medicine of USC
      David W. Craig serves as Vice-Chair of USC's Department of Translational Genomics within the USC Keck School of Medicine. Dr. Craig's expertise is in genomics, bioinformatics, and data analysis of high-throughput genomics data. His laboratory consists of both a wet-lab and dry-lab. Within his group, lab personnel have the opportunity to either specialize or become dual trained in bioinformatics and molecular biology. With collaborators, his group was among the first to implement NGS in molecular profiling for cancer patient treatment recommendations in a feasibility study in metastatic triple-negative breast cancer. Building upon this and other efforts his team developed an end-to-end platform for personalized medicine, NGS data management, analysis, and clinical genomic interpretation following CAP/CLIA guidelines. Within this framework, they completed analytical validation for integrated RNA/DNA analysis of tumor/normal sets. Community resources from these efforts included include a collaborative release of COLO829 tumor/normal sequencing reference sets. He also was a founding scientific director for TGen's Center for Rare Childhood Disorders - a research clinic enrolling over 1000 individuals into a study developing integrative RNA/DNA approaches for identifying the germline genetic basis of disease. As of June 2016, Dr. Craig has moved from Deputy Director of Bioinformatics at TGen to the University of Southern California (USC) where he serves as Co-Director of a new USC Translational Genomics Institute within the USC Keck School of Medicine.


    DATE: November 12, 2019
    TIME: 10:00am PST

    Direct measurement of copy number by droplet-based shallow sequencing of genomic DNA has the potential to provide new insights into tumor heterogeneity and tumor evolution. We examine its utility in a well-studied cancer cell line within a series of tumor specimens. We will demonstrate how clustering based on single cell copy number can help identify subclones that, in turn, make it possible to resolve point mutations, structural variants, and loss of heterozygosity, leading to a clearer picture of overall sample heterogeneity. We will present how we were able to gain significant novel insights—even in well-studied systems—by integrating these clone-specific variants and building models from single cell sequencing of DNA. Finally, we will discuss the design considerations, such as sequencing depth and number of cells, that were important in these studies.


    Learning Objectives:

    • Classify cancer as a dynamic and highly heterogeneous disease composed of a mix of clones characterized by distinct genotypes
    • Recognize the limitations of bulk sequencing methods in resolving subclonal complexity
    • Describe how single cell copy number profiling, together with clustering analysis, can uncover significant hidden insights even in well studied cell lines


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