Genomes To LifeBiology for 21st Century

A Joint Initiative of the Office of Advanced Scientific Computing Research

and Office of Biological and Environmental Researchhttp://DOEGenomesToLife.org

Al GeistDecember 2, 2003

RAM WorkshopOak Ridge, TN

www.genomes-to-life.org

Human Genome ProjectDetermine the Entire DNA Sequence for Humans

New computational tools was key to the success

• All life—plants, animals, insects, and microbes are defined by their genome, which is a long string of four nucleotides A, C, G, T

• Human

– 24 chromosomes contain 6 ft of DNA

– 3 billion nucleotides

– 35,000 genes

– Only 0.0001% difference between people

– Differ by 2 million nucleotides

• Hundreds of genomes have now been done (Bug a month)

• Book of life has 4 letters, words are genes, sentences are machines and regulators. The next step is to determine the sentences

Understand how genes, proteins, and cells work in intricate networks to form dynamic living systems exquisitely responsive to their environment.

Start with simple life form – single cell organism• Discover how microbial genes, proteins and cells work together• Use supercomputers to analyze data, predict, model, and simulate

how protein machines interact through complex interconnected pathways

DOE Genomes to Life Program

BiologyGenomicsproteomics

Math Computer

Science

GTL

Molecular Machines

MicrobialCommunities

Regulatory Pathways

Develop the computational methods and capabilities to advance understanding of complex biological systems

Four Research Areas of Genomes to Life

Understanding the essential processes of living systemsUnderstanding the essential processes of living systems

www.genomes-to-life.org

Molecular Machines Fill CellsMany interlinked proteins form interacting

machines

From The Machinery of Life, David S. Goodsell,

Springer-Verlag, New York, 1993.

www.genomes-to-life.org

Regulatory Networks Control the MachinesGene regulation controls what genes are expressed

Proteome changes over time and due to environmental conditions

Biology is undergoing a major transformation that will be enabled and ultimately driven by computations

Swimming in Data: Exploding Need to Capture and Manipulate DataGTL Knowledge Base:Integration of Large Datasets to do Predictive Modeling

Annotated data setsRaw data sets

Biology for the 21st Century

Models and simulations

www.genomes-to-life.org

Broad Scale of Biological Complexity and Computational Requirements

Understanding metabolic pathways and mechanisms of native microbes

Bioremediation methods for accelerated and less costly cleanup

strategies

Understanding responses of metabolic and regulatory pathways of organisms to environmental conditions

Improved diagnostics and standards for

ecological and human health

Investigating protein expression patterns, protein-protein interactions, and molecular machines

Sensors for detecting pathogens and toxins;

strategies to enable strain identification; and

improved vaccines and therapeutics for combating

infectious disease

Payoffs in the near termSignificant savings in toxic waste cleanup and disposal

Technologies and systems for detecting and responding to biological terrorism

Improve the scientific basis for worker health and safety

Payoffs in the mid to long termHarnessing metabolic pathways/mechanisms in H2-producing microbes

Clean, efficient biological

alternative to fossil fuels

Enable independence of foreign oil

Understanding metabolic pathways and networks, and cell wall synthesis

Designer plants for easily convertible biomass for

fuels, chemical feed stocks, products

Strategies and methods for storing and

monitoring carbon

Stabilize atmospheric carbon dioxide to counter global warming

Investigating enzymes, regulation, environmental cues, and effects

Simulation& Modeling

Tools for Ease of Use

SupercomputerResources

High throughput Experiments

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Biology community

Distributed Databases Human Health Protection

Energy Security

Energy CleanupGenes PathwaysProteins

RACHET

AdvancedComputationalAlgorithms

Integrated Cyclic ProcessIntegrated Cyclic Process