Jacques.van.Heldenulb.ac.be

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Study casesGene expression data

• Statistics Applied to Bioinformatics

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DNA chip technology
Cell culture, tissue, ...
Sample 1
Sample 2
RNA
RNA
RNA extraction
cDNA
cDNA
Synthesis of fluorescent cDNA
Brightness ? Quantity Color ? Specificity

• yellowish not specific
• reddish sample 1 - specific
• greenish sample 2 - specific

DNA chip
Source deRisi et al., Science 1997
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Complete microarray
Source deRisi et al., Science 1997
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DNA chips raw measurements

• Raw measurements
• Red intensity
• Red background
• Green intensity
• Green background
• Intensity background level of expression
• Red in experimental conditions
• Green in control

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DNA chips useful metrics

• The level of regulation is represented by the
  ratio

r gt1 ? up-regulated r lt 1 ? down-regulated

• The log-ratio provides a more convenient
  statistic (we will see why during the course)
• log2 is even more convenient because the scale is
  intuitive

R lt 0 ? down-regulated R gt 0 ? up-regulated
R gt 1 ? regulated by a factor of 2 R gt 2 ?
regulated by a factor of 4 R gt w ? regulated by
a factor of 2w
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Examples of experimental conditions

• Presence/absence of a metabolite
• gal vs glucose
• Transcription factor mutants
• Yap1p overexpression
• TUP1 deletion
• Massive environmental changes
• rich vs minimal medium
• diauxic shift (7 time points during the shift)
• Cell differentiation
• sporulation
• mating type
• Cell cycle

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Late activation during diauxic shift
Data deRisi et al. Science 1997, 278680
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Very late activation during diauxic shift
Data deRisi et al. Science 1997, 278680
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Repression during diauxic shift
Data deRisi et al. Science 1997, 278680