Transcript Final Presentation

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
– Recent success in Thailand energizes efforts
www.dicid.org
Wikimedia.org
“The smallpox, so
fatal, and so general
amongst us, is here
entirely harmless …”
www.wayfaring.info/category/topics/museums/page/9
“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 (?)
Preventable by Vaccine
•
•
•
•
•
•
•
Chickenpox
Diphtheria
Hepatitis A
Hepatitis B
HPV
Flu
Measles
•
•
•
•
•
•
•
Mumps
Pertussis
Rubella
Shingles
Tetanus
Polio
?????HIV?????
Famous
Polio
Survivors
www.tvworthwatching.co
m
www.observer.com
www.lyricsystem.c
www.setileague.
org
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
Many Vaccine Efforts Focus on gp120
• Envelope surface
• Entry into host cell
• Crystallized 1998
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)
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
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)
media.caltech.edu
www.pdb.org
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
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
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
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
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
Conclusions
• Multiple views are a good compromise
between Single-View-Busy-Features and
Single-Feature-Busy-Views
• Ad-hoc predicate view supports scientific
inquiry