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HIViz : Visualizing an HIV Envelope Protein

HIViz : Visualizing an HIV Envelope Protein. Philip Heller CMPS 261 Project Presentation Spring 2010. Motivation. 33M people living with HIV/AIDS 2M children 22M in sub-Saharan Africa 25 years of vaccine research Traditional biomedical approaches Not much visualization

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HIViz : Visualizing an HIV Envelope Protein

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  1. HIViz: Visualizing an HIV Envelope Protein Philip Heller CMPS 261 Project Presentation Spring 2010

  2. Motivation • 33M people living with HIV/AIDS • 2M children • 22M in sub-Saharan Africa • 25 years of vaccine research • Traditional biomedical approaches • Not much visualization • Recent success in Thailand energizes efforts

  3. www.dicid.org

  4. Wikimedia.org

  5. “The smallpox, so fatal, and so general amongst us, is here entirely harmless …” www.wayfaring.info/category/topics/museums/page/9

  6. “The old woman comes with a nut-shell full of the matter of the best sort of small-pox, and asks what vein you please to have opened. She immediately rips open that you offer to her, with a large needle … and puts into the vein as much matter as can lie upon the head of her needle …” “I intend to try it on my dear little son.” Letter from Lady Mary Wortley Montague to Mrs. S. C. 1719 (?)

  7. Preventable by Vaccine • Chickenpox • Diphtheria • Hepatitis A • Hepatitis B • HPV • Flu • Measles • Mumps • Pertussis • Rubella • Shingles • Tetanus • Polio • ?????HIV?????

  8. Famous Polio Survivors www.setileague.org www.observer.com www.lyricsystem.com www.tvworthwatching.com

  9. Why HIV is Different • No one has ever recovered • HIV destroys immune cells • HIV inserts genome into host cell genome, hidden from immune system • HIV evolves constantly/rapidly

  10. Many Vaccine Efforts Focus on gp120 • Envelope surface • Entry into host cell • Crystallized 1998

  11. Berman Lab Data:Primary Sequence Loci of Sites for… • Protease binding (% prevalence) • Possible cutting site • Receptor binding (absent/present) • 1st contact with host cell • Glycosylation (absent/present) • Thick carbohydrate coat, hard to attack • Neutralizing antibodies (absent/present) • Positive selection (all mutations)

  12. Positive Selection • Infection begins with a “founder” individual virus • High mutation rate, rapid reproduction => many variants • Mutations conferring positive or neutral traits are propagated • Selective sweeps • SNP sites are identified, qualified, not quantified

  13. gp120 3D Viz: SOTA • All derived from Wyatt & Kwong 1998 crystallization • Converted to PDB file format • 3D location of all atoms • RasMol, PyMol, JMol forviz & markup • Markup script supplied at: • Startup time (file) • Run time (keyboard)

  14. media.caltech.edu

  15. www.pdb.org

  16. WHAT IF … • What if I could see all features in 3D? • Annotate image with feature observations • Visualize with modified JMol • Goals: • Simultaneously view all 5 features • Predicates eg“Glycosylation –OR– Neutralizing Abs” • Software generation & application of scripts • Extensible: other proteins/features

  17. Simultaneous Viewing of all 5 Features • Too much for 1 image • 5 images: • +: Looks good, easy, supports 6th “predicate” view • -: Very hard to interpret multiple orientation

  18. Solution: “Synchronized Swimming” • Echo mouse events in any window to all others • All zoom/roll/pitch/yaw commands issued identically to all instances • (Probably) novel • JMol not designed for SC/MV • Requires some source-level understanding of Jmol • Glance from image to image without mentally re-orienting

  19. Ad-Hoc Boolean Queries • What sites support protease binding sites are also glycosylation sites? • What sort of mutation happens at antibody neutralization sites? • Predicate-logic combinations of features • A 6th “Predicate” window, + config dialog

  20. Predicate Logic on Numbers • Protease binding: % prevalence • Mutation: What amino acids have been seen at each locus (up to 20, but that’s rare) • Others: Absent/Present • Convert to [0.0 – 1.0] • Prevalence / 100 • Mutation: (# of different amino acids) / 20 • Absent = 0, Present = 1 • Numerical boolean operations: • A or B = max(A,B) • A and B = min(A,B) • Not A = 1 - A Demo Time

  21. Conclusions • Multiple views are a good compromise between Single-View-Busy-Features and Single-Feature-Busy-Views • Ad-hoc predicate view supports scientific inquiry

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