onlineFDR: an R package to control the false discovery rate for growing data repositories

Robertson, David S.; Wildenhain, Jan; Javanmard, Adel; Karp, Natasha A.

doi:10.1093/bioinformatics/btz191

Cited by 23 publications

(24 citation statements)

References 7 publications

(8 reference statements)

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“…Following the similar reasoning in Section 3.1, condition (26) does not conflict with the predictability condition of fs i g 1 i¼1 ; fk i g 1 i¼1 and fa i g 1 i¼1 , even though it apparently requires knowing the whole sequence. To better demonstrate how to construct such sequences, we show an explicit example of ADDIS-Spending algorithm:…”

Section: Addis-spendingmentioning

confidence: 68%

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Online control of the familywise error rate

Tian

Ramdas

2021

Stat Methods Med Res

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Biological research often involves testing a growing number of null hypotheses as new data are accumulated over time. We study the problem of online control of the familywise error rate, that is testing an a priori unbounded sequence of hypotheses ( p-values) one by one over time without knowing the future, such that with high probability there are no false discoveries in the entire sequence. This paper unifies algorithmic concepts developed for offline (single batch) familywise error rate control and online false discovery rate control to develop novel online familywise error rate control methods. Though many offline familywise error rate methods (e.g., Bonferroni, fallback procedures and Sidak’s method) can trivially be extended to the online setting, our main contribution is the design of new, powerful, adaptive online algorithms that control the familywise error rate when the p-values are independent or locally dependent in time. Our numerical experiments demonstrate substantial gains in power, that are also formally proved in an idealized Gaussian sequence model. A promising application to the International Mouse Phenotyping Consortium is described.

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Section: Addis-spendingmentioning

confidence: 68%

“…Note that when L i ¼ 0 for all i, that is the local dependence structure reduces to independence, the above modified procedures reduce to ADDIS-Spending in equation (27).…”

Section: Handling Local Dependencementioning

confidence: 99%

Online control of the familywise error rate

Tian

Ramdas

2021

Stat Methods Med Res

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“…Distributions of expressed cells for top ranked genes were evaluated using the tSNE program in R. Log transformed fold changes (Log2FC) in expression between AD and control samples were evaluated for each of the top-ranked genes within each cell type using the Wilcoxon rank-sum test. False discovery rate (FDR) p-values were adjusted using the Benjamin-Hochberg procedure implemented in R [24].…”

Section: Methodsmentioning

confidence: 99%

Protein phosphatase 2A, complement component 4, and APOE genotype linked to Alzheimer’s disease using a systems biology approach

Jun

You²,

et al. 2020

Preprint

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BackgroundRecent reports suggest that the rare apolipoprotein E (APOE) Christchurch mutation and ε2 allele protect against Alzheimer’s disease (AD) pathology by reducing the burden of tau pathology. However, the mechanism(s) underlying the ε2 protective effect linking to tau is largely unknown.MethodsThe role of the ε2 allele in Alzheimer’s disease (AD) was investigated a genome-wide association study (GWAS) for AD among 2,120 ε2 carriers from the Alzheimer Disease Genetics Consortium (ADGC), and then prioritized by gene network analysis, differential gene expression analysis at tissue- and cell-levels as well as methylation profiling of CpG sites, in prefrontal cortex tissue from 761 brains of the Religious Orders Study and Memory and Aging Project (ROSMAP) and the Framingham Heart Study (FHS), Boston University Alzheimer’s Disease Center (BUADC). The levels of two catalytic subunit proteins from protein phosphatase 2A (PPP2CA and PPP2CB) were validated in prefrontal cortex area of 193 of the FHS/BUADC brains. The findings from human autopsied brains were further validated by a co-culture experiment of human isogenic APOE induced pluripotent stem cell (iPSC) derived neurons and astrocytes.ResultsOf the significantly associated loci with AD among APOE ε2 carriers (P<10−6), PPP2CB (P=1.1×10−7) was the key node in the APOE ε2-related gene network and contained the most significant CpG site (P=7.3×10−4) located 2,814 base pair upstream of the top-ranked GWAS variant. Among APOE ε3/ε4 subjects, the level of Aβ42 was negatively correlated with protein levels of PPP2CA (P=9.9×10−3) and PPP2CB (P=2.4×10−3), and PPP2CA level was correlated with the level of pTau231 level (P=5.3×10−3). Significant correlations were also observed for PPP2CB with complement 4B (C4B) protein levels (P=3.3×10−7) and PPP2CA with cross reactive protein (CRP) levels (P=6.4×10−4). C1q level was not associated with Aβ42, pTau231, PPP2CB, or C4B levels. We confirmed the significant correlation of PPP2CB expression with pTau231/tTau ratio (P=0.01) and C4A/B (P=2.0×10−4) expression observed in brain tissue in a co-culture experiment of iPSC derived neurons and astrocytes.ConclusionWe demonstrated for the first time a molecular link between a tau phosphatase and the classical complement pathway, especially C4, and AD-related tau pathology.

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“…The DEGs were selected according to P ≤ 0.05 and |log FC|≥1 (16, 17). The gene expression level in a specific sample or profile underwent pairwise comparison to generate a score for each gene pair (18).…”

Section: Methodsmentioning

confidence: 99%

Development and Validation of an RNA-Seq-Based Prognostic Signature in Neuroblastoma

et al. 2019

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Objective: The stratification of neuroblastoma (NBL) prognosis remains difficult. RNA-based signatures might be able to predict prognosis, but independent cross-platform validation is still rare.Methods: RNA-Seq-based profiles from NBL patients were acquired and then analyzed. The RNA-Seq prognostic index (RPI) and the clinically adjusted RPI (RCPI) were successively established in the training cohort (TARGET-NBL) and then verified in the validation cohort (GSE62564). Survival prediction was assessed using a time-dependent receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Functional enrichment analysis of the genes was conducted using bioinformatics methods.Results: In the training cohort, 10 gene pairs were eventually integrated into the RPI. In both cohorts, the high-risk group had poor overall survival (OS) (P < 0.001 and P < 0.001, respectively) and favorable event-free survival (EFS) (P = 0.00032 and P = 0.06, respectively). ROC curve analysis also showed that the RPI predicted OS (60 month AUC values of 0.718 and 0.593, respectively) and EFS (60 month AUC values of 0.627 and 0.852, respectively) well in both the training and validation cohorts. Clinicopathological indicators associated with prognosis in the univariate and multivariate regression analyses were identified and added to the RPI to form the RCPI. The RCPI was also used to divide populations into different risk groups, and the high-risk group had poor OS (P < 0.001 and P < 0.001, respectively) and EFS (P < 0.05 and P < 0.05, respectively). Finally, the RCPI had higher accuracy than the RPI for the prediction of OS (60 month AUC values of 0.730 and 0.852, respectively) and EFS (60 month AUC values of 0.663 and 0.763, respectively) in both the training and validation cohorts. Moreover, these differentially expressed genes may be involved in certain NBL-related events.Conclusions: The RCPI could reliably categorize NBL patients based on different risks of death.

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onlineFDR: an R package to control the false discovery rate for growing data repositories

Cited by 23 publications

References 7 publications

Online control of the familywise error rate

Online control of the familywise error rate

Protein phosphatase 2A, complement component 4, and APOE genotype linked to Alzheimer’s disease using a systems biology approach

Development and Validation of an RNA-Seq-Based Prognostic Signature in Neuroblastoma

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