Transcript Why Model? - Richard D. Berlin Center for Cell Analysis

Computational
Biology and Approaches
Raquell M. Holmes, Ph.D.
Computational Biology Workshop
Howard 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
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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
What exists…
Actin polymers: models
http://www.cytochemistry.net/Cell-biology/actin_filaments.htm
Ways of studying properties
• Microscope:
– Watch growth and
shrinkage
– Use fluorescent probes
for growth, shrinkage,
orientation
– Rates of monomer
addition
Myosin, actin, ATP
In_vitro_motility_assay
Gallery
Heart muscle fibers
http://www.psc.edu/research/graphics/ga
llery/heart.html
Daniel Mocanu, Joachim Kettenbach,
Michael O. Sweeney, Bruce H.
KenKnight, Ron Kikinis and Solomon R.
Eisenberg –Boston University
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
Posterior patterns determination
Network for Wing Formation
Conceptual models are changing
Classical View of MAPK Pathways
adapted from C.Roberts, et al., Science, 287, 873 (2000)
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.
Submitted by:
Hirotada MORI
Organism: E.coli
Raw data
MicroArray Data: fold changes in expression
Hypothetical data
Enzyme
hexokinase
Aerobic
++++
Anaerobic
++++
isomerase
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Changes in gene expression:
Single time point,Various conditions
Multiple time points, One condition
GenMapp tools highlight changes
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
•Experimentalist use of confocal microscope
Static 3D image:
microtubules and
cytokinesis (Garry Odell)
•ImageJ, maximum projection
•Digital capture- single processor
Movie source http://raven.zoology.washington.edu/celldynamics/gallery
Views from the
Center for Cell Dynamics
•Experimentalist use of confocal microscope
Live label:
GFP-EB1 in S. droebachiensis.
(Mike Danilchik & George von Dassow)
•Spinning confocal, multiple frame
captures, a single plane
•Digital capture- single processor
Simulation
Movie source http://raven.zoology.washington.edu/celldynamics/gallery
Views from the
Center for Cell Dynamics
Model Animation
Aster microtubules
(George von Dassow)
•assigned color values,
•numerical simulation results.
•multiple processors
Movie source http://raven.zoology.washington.edu/celldynamics/gallery
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 Discipline
Physics, Chemistry, Biology, etc.
Computer Science
Hardware/Software
Applied Mathematics
Numerical Analysis, Modeling,
Simulation
Slide by Kris Stewart, EdCenter, San Diego State University
Elements of Computational
Science
Landau and Yasar, SIAM Review 2003
EPIC-Virtual Institute, 2005
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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
Computational Science:
Interdisciplinary Research and Education
Science Discipline
Physics, Chemistry, Biology, etc.
In the Room
Computer Science
Hardware/Software
Applied Mathematics
Numerical Analysis, Modeling,
Simulation
Slide by Kris Stewart, EdCenter, San Diego State University