scholarly journals A Comparison of Two Classes of Methods for Estimating False Discovery Rates in Microarray Studies

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Emily Hansen ◽  
Kathleen F. Kerr

The goal of many microarray studies is to identify genes that are differentially expressed between two classes or populations. Many data analysts choose to estimate the false discovery rate (FDR) associated with the list of genes declared differentially expressed. Estimating an FDR largely reduces to estimatingπ1, the proportion of differentially expressed genes among all analyzed genes. Estimatingπ1is usually done throughP-values, but computingP-values can be viewed as a nuisance and potentially problematic step. We evaluated methods for estimatingπ1directly from test statistics, circumventing the need to computeP-values. We adapted existing methodology for estimatingπ1fromt- andz-statistics so thatπ1could be estimated from other statistics. We compared the quality of these estimates to estimates generated by two established methods for estimatingπ1fromP-values. Overall, methods varied widely in bias and variability. The least biased and least variable estimates ofπ1, the proportion of differentially expressed genes, were produced by applying the “convest” mixture model method toP-values computed from a pooled permutation null distribution. Estimates computed directly from test statistics rather thanP-values did not reliably perform well.

Author(s):  
Peter Hettegger ◽  
Klemens Vierlinger ◽  
Andreas Weinhaeusel

Abstract Motivation Data generated from high-throughput technologies such as sequencing, microarray and bead-chip technologies are unavoidably affected by batch effects (BEs). Large effort has been put into developing methods for correcting these effects. Often, BE correction and hypothesis testing cannot be done with one single model, but are done successively with separate models in data analysis pipelines. This potentially leads to biased P-values or false discovery rates due to the influence of BE correction on the data. Results We present a novel approach for estimating null distributions of test statistics in data analysis pipelines where BE correction is followed by linear model analysis. The approach is based on generating simulated datasets by random rotation and thereby retains the dependence structure of genes adequately. This allows estimating null distributions of dependent test statistics, and thus the calculation of resampling-based P-values and false-discovery rates following BE correction while maintaining the alpha level. Availability The described methods are implemented as randRotation package on Bioconductor: https://bioconductor.org/packages/randRotation/ Supplementary information Supplementary data are available at Bioinformatics online.


Biometrika ◽  
2011 ◽  
Vol 98 (2) ◽  
pp. 251-271 ◽  
Author(s):  
Bradley Efron ◽  
Nancy R. Zhang

Author(s):  
Balthasar Bickel

Large-scale areal patterns point to ancient population history and form a well-known confound for language universals. Despite their importance, demonstrating such patterns remains a challenge. This chapter argues that large-scale area hypotheses are better tested by modeling diachronic family biases than by controlling for genealogical relations in regression models. A case study of the Trans-Pacific area reveals that diachronic bias estimates do not depend much on the amount of phylogenetic information that is used when inferring them. After controlling for false discovery rates, about 39 variables in WALS and AUTOTYP show diachronic biases that differ significantly inside vs. outside the Trans-Pacific area. Nearly three times as many biases hold outside than inside the Trans-Pacific area, indicating that the Trans-Pacific area is not so much characterized by the spread of biases but rather by the retention of earlier diversity, in line with earlier suggestions in the literature.


PROTEOMICS ◽  
2009 ◽  
Vol 9 (5) ◽  
pp. 1220-1229 ◽  
Author(s):  
Andrew R. Jones ◽  
Jennifer A. Siepen ◽  
Simon J. Hubbard ◽  
Norman W. Paton

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