Clustering%20Algorithms%20to%20make%20sense%20of%20Microarray%20data:%20Systems%20Analyses%20in%20Biology

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Clustering Algorithms to make sense of Microarray
data Systems Analyses in Biology

• Doug Welsh and Brian Davis
• BioQuest Workshop
• Beloit Wisconsin, June 2004

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Biological Questions

• What are the differences between cancer cells and
  normal cells?
• What are the differences in gene expression
  between cancer cells and normal cells?
• Can you guess at the cellular sub-systems that
  may be affected by cancer?
• What are the cellular processes (pathways) that
  might differ between cancer cells and normal
  cells?
• Can you guess at the components (proteins) of the
  pathways that might be involved in cancer

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Goals

• Systems Biology (shift focus among levels of
  knowledge)
• Biology
• Gene Expression (technique)
• Pathways
• DNA Replication
• Individual Proteins
• Math
• Clustering Algorithms (theory and technique)
• Statistics
• Medicine (human phenotype)

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Goals
Cluster
Programming
Medicine
Stats
Math
Biology
Cell Biology
Knowledge
Pathway
Physics
Optics
Robotics
Protein
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Goals
Cluster
Programming
Medicine
Stats
Math
Biology
Cell Biology
Knowledge
Pathway
Physics
Tools
Optics
Robotics
Protein
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Problem Space
Bedrock web site http//bioquest.org/bedrock/prob
lem_spaces/
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Problem Space
DNA Replication Cell Cycle (Depends on Paper)
Microarray Files Gene Annotation
Microarray Analysis Pathway Analysis Statistical
Analysis
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Assumptions

• Assume co-expression of genes has significance.
• We can generate A LOT of data.

Wheat and Chaff

• Clustering algorithms and viewing software allow
  a researcher to focus on subsets of
  (significant) data at a time.

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Project

• Paper Singh D. et al. (2002) Gene expression
  correlates of clinical prostate cancer behavior.
  Cancer Cell Mar1(2)203-9.
• Questions What is the testable hypothesis? How
  is it tested? What are the results? Are the
  conclusions valid?
• Are there other (better?) ways to test this
  hypothesis? Are there better hypotheses to
  formulate?

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Biological Questions

• What are the differences between cancer cells and
  normal cells?
• What are the differences in gene expression
  between cancer cells and normal cells?
• Can you guess at the cellular sub-systems that
  may be affected by cancer?
• What are the cellular processes (pathways) that
  might differ between cancer cells and normal
  cells?
• Can you guess at the components (proteins) of the
  pathways that might be involved in cancer

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Cluster

• Download version 1.4 (v2.2 has bug)
• http//rana.lbl.gov/EisenSoftware.htm
• Load data
• Data transform

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TreeView

• Download latest version
• http//rana.lbl.gov/EisenSoftware.htm
• Load data

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Analysis

• Clustering may reveal organizational units
• What are these proteins and what processes are
  they involved in?

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Next Steps

• Hand off clusters of organizational units to Doug
  (GeneMAPP and MAPPFinder What are these
  proteins in the context of cellular pathways?)
• Investigate interesting single proteins (e.g.,
  with NCBI tools).
• Are these proteins conserved? (do yeast get
  cancer?)
• What is the molecular basis of cancer?

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Goals
Cluster
Medicine
Stats
Math
Biology
Cell Biology
Knowledge
Pathway
Physics
Optics
Robotics
Protein