P53 Pathway Reconstruction Through Integration of Microarray Data

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P53 Pathway ReconstructionThrough Integration of
Microarray Data

• ??? ??? ???

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Functional annotation and network reconstruction
through cross-platform integration of microarray
data

• 2nd--order expression analysis
• 1st-orderexpression patterns
• Ex . 2 fold change Up or down regolation
• 2nd- order correlated occurrences across
  multiple data sets under different conditions
• Using yeast as a model system
• 618 yeast expression profiles comprising 39 cDNA
  or Affymetrix array data sets
• identify genes of the same function without
  coexpression patterns

Nat Biotechnol. 2005 Feb23(2)238-43
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Functional annotation and network reconstruction
through cross-platform integration of microarray
dataNat Biotechnol. 2005 Feb23(2)238-43
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Discussion

• Is the method suitable for human cell model?
• Yeast 5700 genes
• Human 2,2000 genes - more complex!!
• strategy
• Simplify the model and data set
• Focus on special target / pathway
• Add on the biological knowledge

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Project

• Aims
• Reconstruct the p53 transcription network by
  2nd-order analysis method and compare the effect
  of different type of p53
• Model human lymphoblastoid cells
• TK6 p53-wild-type
• WTK1p53-mutant
• NH32p53 knockout
• Dataset
• human 8k cDNA microarray
• (TK6 vs WTK1, TK6 vs NH32 , TK6 vs HN32) x2
• Cell with stress treating (oxidation, Radiation,
  heat shock)
• Compare with the literature result
• Apoptotic signaling pathways induced by nitric
  oxide in human lymphoblastoid cells expressing
  wild-type or mutant p53.Cancer Res. 2004 May
  164(9)3022-9.
• Stress-specific signatures expression profiling
  of p53 wild-type and -null human cells.Oncogene.
  2005 Apr 11

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Apoptotic signaling pathways induced by nitric
oxide in human lymphoblastoid cells expressing
wild-type or mutant p53.Cancer Res. 2004 May
164(9)3022-9.
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Discussion

• Through the 2nd-order analysis, we can compare
  the difference of p53 Transcript network by
  different type of cell.