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

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Presentation on theme: "HIViz: Visualizing an HIV Envelope Protein Philip Heller CMPS 261 Project Presentation Spring 2010."— Presentation transcript:

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

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4 Wikimedia.org

5 “The smallpox, so fatal, and so general amongst us, is here entirely harmless …”

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 …” Letter from Lady Mary Wortley Montague to Mrs. S. C (?) “I intend to try it on my dear little son.”

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

8 Famous Polio Survivors org m om

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) – 1 st 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 for viz & markup Markup script supplied at: – Startup time (file) – Run time (keyboard)

14 media.caltech.edu

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17 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

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

19 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

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21 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 6 th “Predicate” window, + config dialog

22 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

23 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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