Strong Control, Conservative Point Estimation and Simultaneous Conservative Consistency of False Discovery Rates: A Unified Approach

Storey, John D.; Taylor, Jonathan; Siegmund, David

doi:10.1111/j.1467-9868.2004.00439.x

Cited by 1,207 publications

(1,434 citation statements)

References 16 publications

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“…As this represents a substantial number of statistical analyses (84*4 = 336), we controlled for multiple comparisons. In specific, the analyses in this study utilize the false discovery rate (FDR) [14] paradigm for post-hoc hypothesis testing, using the method by Storey [34] in specific. This method produces a substitute or p-values, termed q-values, driven by controlling the proportion of false positives obtained via a set of tests.…”

Section: Resultsmentioning

confidence: 99%

Exploring the Relationships between Design, Students’ Affective States, and Disengaged Behaviors within an ITS

Doddannara

Gowda

Baker

et al. 2013

Lecture Notes in Computer Science

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Abstract.Recent research has shown that differences in software design and content are associated with differences in how much students game the system and go off-task. In particular the design features of a tutor have found to predict substantial amounts of variance in gaming and off-task behavior. However, it is not yet understood how this influence takes place. In this paper we investigate the relationship between a student's affective state, their tendency to engage in disengaged behavior, and the design aspects of the learning environments, towards understanding the role that affect plays in this process. To investigate this question, we integrate an existing taxonomy of the features of tutor lessons [3] with automated detectors of affect [8]. We find that confusion and frustration are significantly associated with lesson features which were found to be associated with disengaged behavior in past research. At the same time, we find that the affective state of engaged concentration is significantly associated with features associated with lower frequencies of disengaged behavior. This analysis suggests that simple re-designs of tutors along these lines may lead to both better affect and less disengaged behavior.

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Section: Resultsmentioning

confidence: 99%

Exploring the Relationships between Design, Students’ Affective States, and Disengaged Behaviors within an ITS

Doddannara

Gowda

Baker

et al. 2013

Lecture Notes in Computer Science

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“…Furthermore, we calculated the false discovery rate (FDR) 61 using the programme largeQvalue 62 . This programme implements the algorithms of refs [63][64][65] , and takes a set of P values and maps these onto q values. We chose a FDR of 0.01, resulting in a threshold of 2.8 × 10 −5 .…”

Section: Nature Ecology and Evolutionmentioning

confidence: 99%

Genomics of habitat choice and adaptive evolution in a deep-sea fish

et al. 2018

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W hile longitudinal and latitudinal habitat transitions have been proposed to define marine communities and promote intraspecific differentiation 1-3 , little is known about the importance of transitions along ocean depth gradients 4,5 , although substantial changes in species assemblages with depth have been recorded (for example, ref. 6 ), and relatively narrow depth ranges may distinguish closely related species (for example, refs 7,8 ). Understanding the relevant mechanisms will contribute significantly to our understanding of eco-evolutionary processes and the origin of marine biodiversity. We chose the roundnose grenadier (Coryphaenoides rupestris) as a model system because it is a widespread species that can inhabit a comparatively broad range of depths 9 from ~180 m to 2,600 m. It is a batch spawner, producing up to 69,000 pelagic eggs per female 10 . It has a spawning season peaking in autumn 11 (recent observations were in September at 1,500 m; ref. 12 ), preys on fish, cephalopods and invertebrates in both benthic and pelagic habitats 13 , and shows minor genetic differentiation across its geographic range [14][15][16] .Adaptation to habitat can occur among populations within a species, and if disruptive selection is associated with assortative mating has the potential to promote incipient speciation through ecological processes in sympatry 17 . When environmental change exposes new habitats and niche potential, adaptive radiations may rapidly generate a new lineage of species 18,19 . To the extent that differential selection can retain polymorphisms within or among populations, this may facilitate the process of adaptive radiation. Here, we focus on one of the key habitat transitions in the oceans-between the photic mesopelagic region and the aphotic regions below (together with the more contiguous changes associated with increasing depth). There is the potential for species (such as the roundnose grenadier), whose habitat range extends across this boundary or along the depth gradient, to experience differential selective pressures. We tested hypotheses about adaptation to these deep-sea habitats using genome sequence data together with data on the ecology and life history of the subject species. We found that juvenile fish of this species are found primarily in relatively shallow depths (near the transition between the mesopelagic and bathypelagic zones) and then migrate as they mature to different depths, and this is strongly associated with their genotype at a set of functional loci. In particular, all adults below ~1,800 m share the same homozygous genotype at each locus. There is evidence for strong selection maintaining this difference, but no clear evidence for differentiation driven by assortative mating. Results and discussionWe produced an annotated reference genome for C. rupestris with a total length of 0.829 gigabase pairs, a mean depth of 104× and an N50 of 159,738 (see Supplementary Methods for details). We used this draft genome to map 60 additional genomes sequenced to a mean depth ...

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“…However, in genetic association studies, most of the hypotheses are null (SNPs not associated with the disease). Moreover, FDR assumes that the P-values corresponding to true null hypothesis tests are independent and uniformly distributed or can be considered as approximately independent [Benjamini and Hochberg, 1995;Storey et al, 2004], which is likely to be violated when there is high LD among SNPs in genetic association studies. Therefore, we compared our method only to the permutation method which is considered as a gold standard in multiple testing correction, Bonferroni and Li and Ji's approach.…”

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confidence: 99%

A multiple testing correction method for genetic association studies using correlated single nucleotide polymorphisms

Gao

Starmer

Martin

2008

Genetic Epidemiology

699

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Multiple testing is a challenging issue in genetic association studies using large numbers of single nucleotide polymorphism (SNP) markers, many of which exhibit linkage disequilibrium (LD). Failure to adjust for multiple testing appropriately may produce excessive false positives or overlook true positive signals. The Bonferroni method of adjusting for multiple comparisons is easy to compute, but is well known to be conservative in the presence of LD. On the other hand, permutation-based corrections can correctly account for LD among SNPs, but are computationally intensive. In this work, we propose a new multiple testing correction method for association studies using SNP markers. We show that it is simple, fast and more accurate than the recently developed methods and is comparable to permutation-based corrections using both simulated and real data. We also demonstrate how it might be used in whole-genome association studies to control type I error. The efficiency and accuracy of the proposed method make it an attractive choice for multiple testing adjustment when there is high intermarker LD in the SNP data set. Genet. Epidemiol. 32:361-369, 2008.r 2008 Wiley-Liss, Inc.Key words: single nucleotide polymorphism; composite linkage disequilibrium; multiple testing correction; principal component analysis; eigenvalues INTRODUCTIONMultiple testing is a challenging issue for genetic data analysis. Candidate gene and genome-wide association studies involve statistical testing of not just a single hypothesis, but many. Even when the point-wise error rate (PWER, a p ) is set to a low level, the experiment-wise error rate (EWER, a e ) increases with the number of tests carried out. For this reason, strict significance thresholds have been recommended to control EWER [Risch and Merikangas, 1996]. However, an overly conservative approach may result in overlooking true positive signals, while an overly liberal criterion could produce excessive false positives. Šidák and Bonferroni corrections are popular approaches for controlling a e by specifying what a p values should be used for each individual test. The Šidák correction is calculated as a p ¼ 1 À ð1 À a e Þ 1=N , where N is the number of individual hypotheses to be tested [Šidák, 1967]. This correction assumes that the hypothesis tests are independent. Noting that ð1 À a p Þ N % 1 À Na p for small a p , we obtain the Bonferroni correction as Bonferroni, 1935Bonferroni, , 1936, which is an approximation to the Šidák correction.Recently, single nucleotide polymorphisms (SNPs), which are often densely genotyped, have become popular markers for genetic association studies. The closely spaced SNPs frequently yield high correlation because of extensive linkage disequilibrium (LD) among them [Wall and Pritchard, 2003]. Therefore, when association studies are conducted with many SNPs, the tests performed on each SNP are usually not independent, depending on the correlation structure among the SNPs. This violation of the independence assumption limits the Šidák and Bonferron...

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Strong Control, Conservative Point Estimation and Simultaneous Conservative Consistency of False Discovery Rates: A Unified Approach

Cited by 1,207 publications

References 16 publications

Exploring the Relationships between Design, Students’ Affective States, and Disengaged Behaviors within an ITS

Exploring the Relationships between Design, Students’ Affective States, and Disengaged Behaviors within an ITS

Genomics of habitat choice and adaptive evolution in a deep-sea fish

A multiple testing correction method for genetic association studies using correlated single nucleotide polymorphisms

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