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Multiple hypothesis testing adjusted for latent variables, with an application to the AGEMAP gene expression data. (English) Zbl 1257.62115

Summary: In high throughput settings we inspect a great many candidate variables (e.g., genes) searching for associations with a primary variable (e.g., a phenotype). High throughput hypothesis testing can be made difficult by the presence of systemic effects and other latent variables. It is well known that those variables alter the level of tests and induce correlations between tests. They also change the relative ordering of significance levels among the hypotheses. Poor rankings lead to wasteful and ineffective follow-up studies. The problem becomes acute for latent variables that are correlated with the primary variable.
We propose a two-stage analysis to counter the effects of latent variables on the ranking of hypotheses. Our method, called LEAPP, statistically isolates the latent variables from the primary one. In simulations, it gives better ordering of the hypotheses than competing methods such as SVA and EIGENSTRAT. For an illustration, we turn to data from the AGEMAP study relating gene expression to age for 16 tissues in the mouse. LEAPP generates rankings with greater consistency across tissues than the rankings attained by the other methods.

MSC:

62P10 Applications of statistics to biology and medical sciences; meta analysis
92D10 Genetics and epigenetics
62J15 Paired and multiple comparisons; multiple testing
65C60 Computational problems in statistics (MSC2010)

Software:

leapp; FAMT; Eigenstrat
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Full Text: DOI arXiv Euclid

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