Systems Biology

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Systems Biology

• Fundamentals of Bioinformatics
• Bruce Byrne, PhD
• February, 2008

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Systems Biology Definitions

• integrate high-throughput biological studies to
  understand how biological systems function.
  relationships and interactions between various
  parts of a biological system . (Wikipedia)
• Comprehensive, methodical analysis of complex
  biological systems by monitoring responses to
  perturbations of biological processes. Large
  scale, computerized collection and analysis of
  the data are used to develop and test models of
  biological systems.Year introduced 2005 (MeSH
  heading)
• study of an organism, viewed as an integrated
  and interacting network of genes, proteins and
  biochemical reactions which give rise to life
  (Institute for Systems Biology, Seattle Lee
  Hood)
• discover on a systems level how biological
  molecules interact and respond to their
  environment using advanced computational methods.
  (Princeton Center for Quantitative Biology
  David Botstein)

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Attributes Claimed for Systems Biology

• Non-reductive
• Integrative
• Predictive
• Explicative
• What do these mean?

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Origins of Systems BiologyDiscuss

• Ecology
• 1930s Ecosystem
• Study of the interactions between living things
  and their natural (physical/biological)
  environments
• Bacterial Genetics
• 1960 The lac Operon (Jacob Monod)
• Feedback regulation from a set of linked genes
• Enzymology
• Allosteric transitions
• Metabolic cascades
• 1981 Goldbeter and Koshland (1981) Non-linear
  response in phosphorylation kinetics and cascade
  phenomena
• MAPK Mitogen activating protein kinases

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An Informatics Approach to Systems KEGG

• Kyoto Encyclopedia of Genes and Genomes
• Links information about genomes to biological
  systems
• A family of databases with cross-links
• Pathways/BRITE
• Genes/KO
• Ligand

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KEGG Pathways Pathway Maps

• http//www.genome.jp/kegg/kegg1a.html
• Metabolism
• Genetic Information Processing
• Environmental Information Processing
• Cellular Processes
• Human Diseases

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KEGG BRITE http//www-tsujii.is.s.u-tokyo.ac.jp/j
w-tmnlpo/SusumuGOTO.pdf

• Hierarchical, functional annotation and
  integration of databases
• Controlled, cross-referenced vocabulary with
  other repositories
• Example KEGG GENES IDlt-gt NCBI-GI, GeneID
• Functions defined by annotators and experts
• Potential to go beyond traditional pathways

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Protein Families in KEGG BRITE

• Enzymes
• Cytochrome P450
• Transcription factors
• Ribosome
• Translation factors
• ABC transporters
• G-protein coupled receptors
• GTP-binding proteins

• Ion channels
• Cytokines
• Cytokine receptors
• Cell adhesion molecules (CAMs)
• CAM ligands
• CD molecules
• Bacterial motility proteins

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KEGG Chemical (Ligands)

• http//www.genome.jp/kegg/reaction/
• Compound
• Biological roles, classes of compounds, etc.
• Tries to group by function
• Drug
• Therapeutic categories
• Formal classes of drugs
• Glycan
• Reaction
• RPAIR
• Enzyme

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KEGG Definitions

• E.C. definitions relationship to other ways of
  thinking about genes and proteins
• http//www.expasy.ch/enzyme/
• Ligands
• Enzymes
• Small molecules
• Drugs
• KEGG Organism Codes

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Exercise for In-Class Discussion

• KEGG speaks in a very formal language. Try your
  luck with KEGG Identifiers
• http//www.genome.jp/kegg/kegg3.html
• Compare and contrast to NCBI identifiers
• Group 1
• Search KEGG for MAPK
• What kinds of classifications do you observe?
• What are the links to NCBI (or other databases)
• Group 2
• Search KEGG BRITE for the term penicillin
• How can you view the world of penicillin in KEGG?
• What are the links to NCBI (or other databases)