1. Computational Biology and Approaches Raquell M. Holmes, Ph.D. Computational Biology Workshop Howard University and Boston University August 15, 2005

2. This morning Computational Biology –Snapshots of existing models –Transition in biological views Computing and computational science

3. 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

4. Computational Biology: Dynamics Jacquet et al 2003, JCB

5. What exists…

6. http://www.cytochemistry.net/Cell-biology/actin_filaments.htm Actin polymers: models

7. Ways of studying properties Microscope: –Watch growth and shrinkage –Use fluorescent probes for growth, shrinkage, orientation –Rates of monomer addition In_vitro_motility_assay Myosin, actin, ATP

8. Gallery Daniel Mocanu, Joachim Kettenbach, Michael O. Sweeney, Bruce H. KenKnight, Ron Kikinis and Solomon R. Eisenberg –Boston University Heart muscle fibers http://www.psc.edu/research/graphics/ga llery/heart.html

9. 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, Amsterdamwww.mcell.psc.edu/DReAMM

10. Posterior patterns determination

11. Network for Wing Formation

12. Conceptual models are changing

13. Classical View of MAPK Pathways adapted from C.Roberts, et al., Science, 287, 873 (2000)

14. 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)

15. 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.

16. Raw data Submitted by: Hirotada MORI Organism: E.coli

17. EnzymeAerobicAnaerobic hexokinase++++ isomerase----++ MicroArray Data: fold changes in expression Changes in gene expression: Single time point,Various conditions Multiple time points, One condition GenMapp tools highlight changes Hypothetical data

18. Views from the Center for Cell Dynamics Experimentalist use of confocal microscope –Static 3D image: microtubules and cytokinesis (Garry Odell)Static 3D image –Live label: GFP-EB1 in S. droebachiensis. (Mike Danilchik & George von Dassow)Live label Model Animation –Aster microtubules ( George von Dassow)Aster microtubules

19. Views from the Center for Cell Dynamics Static 3D imageStatic 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

20. Views from the Center for Cell Dynamics Live labelLive 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

21. 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

22. 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

23. 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

24. Elements of Computational Science Landau and Yasar, SIAM Review 2003 EPIC-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

25. 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)

26. CI Vision http://www.nsf.gov/news/special_reports/cyber/index.jsp

27. 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 In the Room