Transcript What are the differences between Cancer cells and Normal

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?
 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
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)
Cluster
Stats
Goals
Programming
Medicine
Math
Biology
Physics
Optics
Robotics
Knowledge
Cell Biology
Pathway
Protein
Cluster
Stats
Goals
Programming
Medicine
Math
Biology
Physics
Optics
Robotics
Knowledge
Cell Biology
Pathway
“Tools”
Protein
Problem Space
Bedrock web site: http://bioquest.org/bedrock/problem_spaces/
Problem Space
DNA Replication
Cell Cycle
(Depends on Paper)
Microarray Analysis
Pathway Analysis
Statistical Analysis
Microarray Files
Gene Annotation
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.
Project
Paper: 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 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
Cluster
Download:
version 1.4 (v2.2
has bug):
http://rana.lbl.gov
/EisenSoftware.h
tm
Load data
Data
transform***
TreeView
Download
latest version
http://rana.lbl.
gov/EisenSoft
ware.htm
Load data
Analysis
Clustering
may reveal
organizational
units
What are
these proteins
and what
processes are
they involved
in?
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?
Goals
Cluster
Medicine
Stats
Math
Biology
Physics
Optics
Robotics
Knowledge
Cell Biology
Pathway
Protein