clustering algorithms to make sense of microarray data: systems analyses in biology
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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. Biological Questions. What are the differences between cancer cells and normal cells? - PowerPoint PPT PresentationTRANSCRIPT
Clustering Algorithms to make sense of Microarray data:
Systems Analyses in Biology
Doug Welsh and Brian Davis BioQuest Workshop
Beloit Wisconsin, June 2004
Biological QuestionsWhat 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
GoalsSystems 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)
Goals
Knowledge
Cluster
Stats Math
Physics
Optics
Biology
Medicine
Cell Biology
Pathway
ProteinRobotics
Programming
Goals
Knowledge
Cluster
Stats Math
Physics
Optics
Biology
Medicine
Cell Biology
Pathway
Protein“Tools”
Robotics
Programming
Problem Space
Bedrock web site: http://bioquest.org/bedrock/problem_spaces/
Problem SpaceDNA Replication
Cell Cycle(Depends on Paper)
Microarray FilesGene Annotation
Microarray AnalysisPathway Analysis
Statistical Analysis
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.
ProjectPaper: Singh D. et al. (2002) Gene expression correlates of clinical prostate cancer behavior. Cancer Cell Mar;1(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?
Biological QuestionsWhat 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
ClusterDownload: version 1.4 (v2.2 has bug):http://rana.lbl.gov/EisenSoftware.htmLoad dataData transform***
TreeViewDownload latest versionhttp://rana.lbl.gov/EisenSoftware.htmLoad data
AnalysisClustering may reveal organizational unitsWhat are these proteins and what processes are they involved in?
Next StepsHand 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?
Goals
Knowledge
Cluster
Stats Math
Physics
Optics
Biology
Medicine
Cell Biology
Pathway
ProteinRobotics