multiple testing etc
DESCRIPTION
Multiple testing etc. Benjamin Neale Leuven 2008. Technology advances – Affy 500K. How the Affy Chip works. Illumina’s Chip. Multiple testing approaches. Bonferroni Correction Conservative Probability of observing at least 1 hit at that level False Discovery methodology - PowerPoint PPT PresentationTRANSCRIPT
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Multiple testing etc.
Benjamin Neale
Leuven 2008
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Technology advances – Affy 500K
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How the Affy Chip works
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Illumina’s Chip
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Multiple testing approaches
• Bonferroni Correction– Conservative– Probability of observing at least 1 hit at that level
• False Discovery methodology– Capitalizes on a distribution of positive results– See work by Benjamin, Hochberg, Storey
• Bayes Factor– Like a P-value, but for Bayesians– Marginal likelihood of the two sets of parameters– Correlation approaches 1 under the alternative
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Genome-wide significance
• Multiple testing theory requires an estimate of the number of ‘independent tests’
• Risch and Merikangas 1996 estimated a threshold of 10-6 = (0.05/(5*10000))
• HapMap 2005 estimate 10-8 based on encode deep sequencing in ENCODE regions
• Dudbridge and Gusnato and Pe’er et al. 2008 Genetic Epidemiology estimate based on ‘infinite density’ like Lander and Kruglyak 1995 generates 5x10-8
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Guessing game
• I’ll buy a beer for the closest guess
• We’re each going to simulate a single chi square
• There are about 25 groups
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Distribution of chi squares
1 df chi square expectation
Distribution of maximum 1 df chi square from 25 trials
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QQ plotting
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QQ plotting
Expectation
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QQ plotting
Observation
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QQ plotting
Observation
Expectation
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QQ plotting
Observation
Expectation
Above the line indicates inflation of the test statistic
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QQ plotting
Observation
Expectation
Below the line indicates deflation of the test statistic
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Plotting the results in R
CHANGE DIR…
This is the menu item you must change to change where the PLINK results file is found
Note you must have the R console highlighted
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Picture of the dialog box
Either type the path name or browse to where you saved plink.cmh
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Screenshot of source code selection
This is the file qqplot.R for the source code