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

What exists…

http://www.cytochemistry.net/Cell-biology/actin_filaments.htm

Actin polymers: models

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

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.

Raw data

Submitted by: Hirotada MORI

Organism: E.coli

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

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

In the Room