Challenges in Computational Molecular Biology

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Challenges in Computational Molecular Biology

• Martin Tompa
• Computer Science Engineering
• Genome Sciences
• University of Washington
• Seattle, Washington, U.S.A.

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Do Biologists Need Help?

• An organisms genome is the total DNA in one of
  its cells.
• How many nucleotides in a genome?
• M. tuberculosis bacterium 4,000,000
• D. melanogaster fruit fly 200,000,000
• H. sapiens human 3,000,000,000
• P. nudum whisk fern 250,000,000,000
• Wet-lab work is costly and time-consuming

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Human Genome

• Human genome sequenced in 2001
• Determined the precise sequence of 3,000,000,000
  As, Cs, Gs, Ts
• Why was this important?
• Very first step in understanding the program that
  controls cell processes

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9 Future Challenges for Bioinformatics

• Adapted from an article by
• E. Birney, C. Burge, and J. Fickett, Genome
  Technology, issue 17, Jan. 2002

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9 Future Challenges for Bioinformatics

• 1 Precise model of transcription initiation and
  termination ability to predict where, when, and
  at what rate transcription will occur

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Endo16 Regulatory Network
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9 Future Challenges for Bioinformatics

• 2 Precise model of RNA splicing ability to
  predict the splicing pattern of any primary
  transcript in any tissue

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9 Future Challenges for Bioinformatics

• 3 Precise model of signal transduction
  pathways ability to predict cellular responses
  to external stimuli

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EGF Recepter Signaling Pathway
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9 Future Challenges for Bioinformatics

• 4 Precise model for the following binding
  interactions
• protein-DNA
• protein-RNA
• protein-protein
• RNA-RNA

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Zinc Finger DNA Binding
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9 Future Challenges for Bioinformatics

• 5 Accurate ab initio RNA structure prediction

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SARS s2m RNA
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9 Future Challenges for Bioinformatics

• 6 Accurate ab initio protein structure
  prediction

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Structure of ß-amylase
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9 Future Challenges for Bioinformatics

• 7 Rational design of small molecule inhibitors
  of proteins

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Fasciculin Docked with AChE
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9 Future Challenges for Bioinformatics

• 8 Development of gene ontologies systematic
  ways to describe and predict the functions of any
  gene or protein

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9 Future Challenges for Bioinformatics

• 9 Precise model of evolution understanding
  exactly how biological sequences evolve

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HERV-K Retrovirus Insertions
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Other Challenges

• Development how do cells specialize?
• Speciation what is the mechanism?
• Disease models diagnosis, prognosis, treatment
• Drug design discovery, validation, development
• Individualized medicine

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Relevant Math. Comp. Sci.

• Probability and statistics
• Combinatorics
• Information theory
• Mathematical modeling
• Algorithm design and analysis
• Databases
• Machine learning
• Text mining, natural language processing
• Image processing
• User interfaces