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ComputationalBiology and Approaches
Raquell M. Holmes, Ph.D.
Computational Biology WorkshopHoward University and Boston University
August 15, 2005
This morning
Computational Biology– Snapshots of existing models– Transition in biological views
Computing and computational science
Computational Biology
• Bioinformatics, Genomics, Proteomics, Metabolome• Sequences analysis and comparison• Database searches • Statistics, Graph theory, Strings, Markov Models• High throughput data generation
• Protein structure, folding, energy– Molecular dynamics, Monte Carlo
Computational Biology: Dynamics
Jacquet et al 2003, JCB
Ways of studying properties
• Microscope:– Watch growth and
shrinkage
– Use fluorescent probes for growth, shrinkage, orientation
– Rates of monomer addition
In_vitro_motility_assayMyosin, actin, ATP
Gallery
Daniel Mocanu, Joachim Kettenbach, Michael O. Sweeney, Bruce H. KenKnight, Ron Kikinis and Solomon R. Eisenberg –Boston University
Heart muscle fibershttp://www.psc.edu/research/graphics/gallery/heart.html
Neuromuscular junction …
All images were produced by Joel Stiles using DReAMM (www.mcell.psc.edu/DReAMM) software. Citation: Stiles, JR, Ford, WC, Pattillo, JM, Deerinck, TE, Ellisman, MH, Bartol, TM, and Sejnowski, TJ. (2004) Spatially realistic computational physiology: past, present, and future. In: Parallel Computing: Software Technology, Algorithms, Architectures & Applications, ed. Joubert, G, et al. Elsevier, Amsterdam
The Protein Network View• Highly interconnected, not
just a linear pathway!
• Some proteins are missing from the protein interaction data sets (Cdc42, Ste20).
• Includes several additional proteins (especially Akr1, Kss1).
adapted from C.Roberts, et al., Science, 287, 873 (2000)
Expression data
• KEGG: – retrievable expression data sets
• EcoCyc: – input expression data to view in relation to
metabolic data.
• Expression data is one way of viewing the behavior of a system.
Enzyme Aerobic Anaerobic
hexokinase ++++ ++++
isomerase ---- ++
MicroArray Data: fold changes in expression
Changes in gene expression:Single time point,Various conditionsMultiple time points, One condition
GenMapp tools highlight changes
Hypothetical data
Views from the Center for Cell Dynamics
• Experimentalist use of confocal microscope– Static 3D image: microtubules and cytokinesis
(Garry Odell)
– Live label: GFP-EB1 in S. droebachiensis. (Mike Danilchik & George von Dassow)
• Model Animation– Aster microtubules (George von Dassow)
Views from the Center for Cell Dynamics
Static 3D image: microtubules and cytokinesis (Garry Odell)
•Experimentalist use of confocal microscope
Movie source http://raven.zoology.washington.edu/celldynamics/gallery
•ImageJ, maximum projection
•Digital capture- single processor
Views from the Center for Cell Dynamics
Live label: GFP-EB1 in S. droebachiensis. (Mike Danilchik & George von Dassow)
•Experimentalist use of confocal microscope
Movie source http://raven.zoology.washington.edu/celldynamics/gallery
•Spinning confocal, multiple frame captures, a single plane
•Digital capture- single processor Simulation
Views from the Center for Cell Dynamics
Model Animation
Aster microtubules (George von Dassow)
Movie source http://raven.zoology.washington.edu/celldynamics/gallery
•assigned color values,
•numerical simulation results.
•multiple processors
What do we discover?
• New questions: • Hysteresis in cell cycle
• New understandings and conceptual models:
• Metabolic control analysis
• Missing pieces: • Calcium dynamics in neuroblastoma cells
Computational Science:Interdisciplinary Research and Education
Science DisciplinePhysics, Chemistry, Biology, etc.
Computer ScienceHardware/Software
Applied MathematicsNumerical Analysis, Modeling,
Simulation
Slide by Kris Stewart, EdCenter, San Diego State University
Elements of Computational Science
Landau and Yasar, SIAM Review 2003EPIC-Virtual Institute, 2005
• Computational tools• High performance computing*• Applied mathematics and computational methods*• Application in science and engineering*• Simulation and modeling• Visualization tools• Large scale data sets: statistical and visual analysis
What is Supercomputing?Leading Edge to Consumer Electronics
1985 Cray X-MP: 1.2 Gflop
Cost:$8,000,000
60,000 watts of power
No Built in Graphics
56 kbps NSFnet Backbone
2005 X-Box: ~5 Gflop peak
Cost: $140
~100 watts of power
3D Graphics (125M P/S)
(100 Mbps etherNet)
CI Vision
http://www.nsf.gov/news/special_reports/cyber/index.jsp