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UCSC Immunobrowser

UCSC Immunobrowser. Hyunsung John Kim 10/16/2013. UCSC Immunobrowser. Analyze status of Adaptive Immune System Tracks T-cells based on sequence signature in the T-Cell Receptor Beta Targeted Next Generation Sequencing generates billions of data points

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UCSC Immunobrowser

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  1. UCSC Immunobrowser Hyunsung John Kim 10/16/2013

  2. UCSC Immunobrowser • Analyze status of Adaptive Immune System • Tracks T-cells based on sequence signature in the T-Cell Receptor Beta • Targeted Next Generation Sequencing generates billions of data points • Can we provide Repertoire-level analysis while preserving Receptor-level detail • Search the literature for clues on T-cell function

  3. Adaptive Immune System • Specific • Receptors to bind exclusively to a pathogen • Diverse • Receptors can be designed to almost any pathogen • Memory • Predesigned receptors are reused for subsequent infections • Self/non-self recognition • T-Cells/B-Cells do not attack healthy self cells

  4. Specific and Diverse Receptors • Each receptor has a unique genome sequence

  5. Memory

  6. What do B-cells and T-cells do? http://www.hu.liu.se/ike/forskning/cellbiologi/rosen-anders/rosen/1.264183/Bcell200.jpg http://www.unm.edu/~mpachman/Blood/t_cell_killing_cancer_cell.jpg Sciencephoto.com

  7. Complementarity Determining Regions (CDR) determine binding specificity Tertiary: Secondary: Primary:

  8. Specific and Diverse Receptors CDRs

  9. Random Receptor Sequence generated through VDJ Recombination • ~1015-1020 Distinct TCR sequences • Diversity generated through: • Combinatorial Joining (left) • Random Nucleotide addition

  10. Clonal Expansion Shapes the Repertoire http://163.16.28.248/bio/activelearner/43/ch43c3.html

  11. What is an Immune Repertoire? • Set of all BCR and TCR sequences in an individual • 1011 B-cells and T-cells

  12. Immunosequencing Workflow

  13. Assay Modified from Warran, et al 2009

  14. High throughput sequencers 454 Titanium IlluminaHiSeq Short reads 2x100bp Paired-end reads High throughput 3 x 109reads Preferred for T-cells • Long reads • ~600bp reads • Medium throughput • 106 reads • Preferred for B-cells

  15. Junctional Analysis

  16. VJ gene segment usage Wang et al, 2010 Robins et al, 2009 Boyd et al, 2009 Weinstein et al, 2009

  17. UCSC Immunobrowser • Takes in annotated sequence data • Generates Repertoire-level visuals • Persistent filters view subsets of a repertoire • Track clonal expansions over multiple samples • Identify aberrant clonal expansions (Blood cancers) • Track clonal expansions (Immune response) • Search literature • RESTfulurls makes sharing easy • (Dev) http://laozi.soe.ucsc.edu:8000

  18. The Future • Motif Finding • Group vs group comparisons • The personal sequencer • Regular TCR/IG sequencing • Integration with Medbook-like service • Detect reoccurence of disease or relapse of autoimmune disease • Know if you’ve got the flu or a cold

  19. Fin. • Thanks to: • Max Haeussler • Ngan Nguyen • You, for your time • Questions?

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