False Discovery Control for Scan Clustering

2009 ◽  
pp. 271-287
Author(s):  
Marco Perone-Pacifico ◽  
Isabella Verdinelli
Keyword(s):  
False Discovery

Decrease in Secondary Neck Vessels in Multiple Sclerosis: A 5-year Longitudinal Magnetic Resonance Angiography Study

2019 ◽  
Vol 16 (3) ◽  
pp. 215-223 ◽  
Author(s):  
Dejan Jakimovski ◽  
Matthew Topolski ◽  
Kana Kimura ◽  
Virja Pandya ◽  
Bianca Weinstock-Guttman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Magnetic Resonance Angiography ◽  
Longitudinal Change ◽  
Repeated Measure ◽  
Cross Sectional ◽  
False Discovery ◽  
The Common ◽  
Neck Vessels

Background: Studies have previously shown greater arterial and venous extracranial vascular changes in persons with multiple sclerosis (PwMS) when compared to healthy controls (HCs). Objectives: To determine the change in the number and size of secondary neck vessels in PwMS and HCs over a 5-year follow-up period. Methods: Both at baseline and follow-up, 83 PwMS and 25 HCs underwent magnetic resonance angiography (MRA) imaging and analysis. The number and cross-sectional area (CSA) of all secondary neck vessels (excluding the common/internal carotid, vertebral artery, and internal jugular vein) measured at levels from C2-T1 were determined by semi-automated edge detection/ contouring software. The longitudinal change in the number and CSA of the secondary neck vessels from the PwMS and HCs were analyzed by non-parametric Wilcoxon repeated measure. Benjamini-Hochberg procedure adjusted for false discovery rate (FDR). Results: For over 5 years, PwMS demonstrated a consistent longitudinal decrease in both the number of secondary neck vessels (Z-change between -3.3 and -5.4, q=0.001) and their CSA (Zchange between -2.9 and -5.2, q=0.004). On the contrary, the HCs did not demonstrate a significant longitudinal change in secondary neck vessels over the follow-up period. Due to the longitudinal decrease, the PwMS showed a lower number of secondary neck vessels when compared to HCs measured at follow-up (p<0.029, except for C4 with trending p=0.071). The PwMS changes were also corroborated within each MS phenotype. Conclusion: PwMS demonstrate a significant mid-term decrease in the number and the size of the secondary neck vessels. The clinical relevance of these findings and the effect on intracranial blood flow are currently unknown.

scholarly journals 2dFDR: a new approach to confounder adjustment substantially increases detection power in omics association studies

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sangyoon Yi ◽  
Xianyang Zhang ◽  
Lu Yang ◽  
Jinyan Huang ◽  
Yuanhang Liu ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Statistical Power ◽  
Association Studies ◽  
Control Procedure ◽  
Multiple Testing Correction ◽  
New Approach ◽  
False Discovery ◽  
Traditional Procedure ◽  
Extensive Evaluation ◽  
Confounder Adjustment

AbstractOne challenge facing omics association studies is the loss of statistical power when adjusting for confounders and multiple testing. The traditional statistical procedure involves fitting a confounder-adjusted regression model for each omics feature, followed by multiple testing correction. Here we show that the traditional procedure is not optimal and present a new approach, 2dFDR, a two-dimensional false discovery rate control procedure, for powerful confounder adjustment in multiple testing. Through extensive evaluation, we demonstrate that 2dFDR is more powerful than the traditional procedure, and in the presence of strong confounding and weak signals, the power improvement could be more than 100%.

scholarly journals Transcriptome Analyses of Myometrium from Fibroid Patients Reveals Phenotypic Differences Compared to Non-Diseased Myometrium

2021 ◽  
Vol 22 (7) ◽  
pp. 3618
Author(s):  
Emmanuel N. Paul ◽  
Gregory W. Burns ◽  
Tyler J. Carpenter ◽  
Joshua A. Grey ◽  
Asgerally T. Fazleabas ◽  
...  
Keyword(s):  
Uterine Fibroid ◽  
Three Dimensional ◽  
Uterine Fibroids ◽  
Principal Component ◽  
Leading Edge ◽  
Gene Set Enrichment ◽  
Phenotypic Differences ◽  
False Discovery ◽  
Gene Sets ◽  
High Concordance

Uterine fibroid tissues are often compared to their matched myometrium in an effort to understand their pathophysiology, but it is not clear whether the myometria of uterine fibroid patients represent truly non-disease control tissues. We analyzed the transcriptomes of myometrial samples from non-fibroid patients (M) and compared them with fibroid (F) and matched myometrial (MF) samples to determine whether there is a phenotypic difference between fibroid and non-fibroid myometria. Multidimensional scaling plots revealed that M samples clustered separately from both MF and F samples. A total of 1169 differentially expressed genes (DEGs) (false discovery rate < 0.05) were observed in the MF comparison with M. Overrepresented Gene Ontology terms showed a high concordance of upregulated gene sets in MF compared to M, particularly extracellular matrix and structure organization. Gene set enrichment analyses showed that the leading-edge genes from the TGFβ signaling and inflammatory response gene sets were significantly enriched in MF. Overall comparison of the three tissues by three-dimensional principal component analyses showed that M, MF, and F samples clustered separately from each other and that a total of 732 DEGs from F vs. M were not found in the F vs. MF, which are likely understudied in the pathogenesis of uterine fibroids and could be key genes for future investigation. These results suggest that the transcriptome of fibroid-associated myometrium is different from that of non-diseased myometrium and that fibroid studies should consider using both matched myometrium and non-diseased myometrium as controls.

scholarly journals False Discovery Rate in Linkage and Association Genome Screens for Complex Disorders

Genetics ◽  
2003 ◽  
Vol 164 (2) ◽  
pp. 829-833
Author(s):  
Chiara Sabatti ◽  
Susan Service ◽  
Nelson Freimer
Keyword(s):  
Gene Mapping ◽  
False Discovery Rate ◽  
Disease Gene ◽  
Susceptibility Genes ◽  
Complex Disorders ◽  
Disease Gene Mapping ◽  
False Discovery ◽  
Simple Step ◽  
Multiple Comparison Procedure ◽  
Step Down

Abstract We explore the implications of the false discovery rate (FDR) controlling procedure in disease gene mapping. With the aid of simulations, we show how, under models commonly used, the simple step-down procedure introduced by Benjamini and Hochberg controls the FDR for the dependent tests on which linkage and association genome screens are based. This adaptive multiple comparison procedure may offer an important tool for mapping susceptibility genes for complex diseases.

scholarly journals P14.21 Tehila Kaisman-Elbaz MD/PhD

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii71-iii71
Author(s):  
T Kaisman-Elbaz ◽  
Y Elbaz ◽  
V Merkin ◽  
L Dym ◽  
A Noy ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
False Discovery Rate ◽  
Medical Center ◽  
Tumor Resection ◽  
Multiple Hypothesis Testing ◽  
Hemoglobin Level ◽  
Distribution Width ◽  
False Discovery ◽  
Dismal Prognosis

Abstract BACKGROUND Glioblastoma is known for its dismal prognosis though its dependency on patients’ readily available RBCs parameters defining the patient’s anemic status such as hemoglobin level and Red blood cells distribution Width (RDW) is not fully established. Several works demonstrated a connection between low hemoglobin level or high RDW values to overall glioblastoma patient’s survival, but in other works, a clear connection was not found. This study addresses this unclarity. MATERIAL AND METHODS In this work, 170 glioblastoma patients, diagnosed and treated in Soroka University Medical Center (SUMC) in the last 12 years were retrospectively inspected for their survival dependency on pre-operative RBCs parameters using multivariate analysis followed by false discovery rate procedure due to the multiple hypothesis testing. A survival stratification tree and Kaplan-Meier survival curves that indicate the patient’s prognosis according to these parameters were prepared. RESULTS Beside KPS>70 and tumor resection supplemented by oncological treatment, age<70 (HR=0.4, 95% CI 0.24–0.65), low hemoglobin level (HR=1.79, 95% CI 1.06–2.99) and RDW<14% (HR=0.57, 95% CI 0.37–0.88) were found to be prognostic to patients’ overall survival in multivariate analysis, accounting for false discovery rate of less than 5%. CONCLUSION A survival stratification highlighted a non-anemic subgroup of nearly 30% of the cohort’s patients whose median overall survival was 21.1 months (95% CI 16.2–27.2) - higher than the average Stupp protocol overall median survival of about 15 months. A discussion on the beneficial or detrimental effect of RBCs parameters on glioblastoma prognosis and its possible causes is given.

scholarly journals Associations Between Genetically Predicted Protein Levels and COVID-19 Severity

2020 ◽  
Vol 223 (1) ◽  
pp. 19-22
Author(s):  
Jingjing Zhu ◽  
Chong Wu ◽  
Lang Wu
Keyword(s):  
False Discovery Rate ◽  
Drug Repurposing ◽  
Bonferroni Correction ◽  
Host Genetics ◽  
Protein Levels ◽  
False Discovery

Abstract It is critical to identify potential causal targets for SARS-CoV-2, which may guide drug repurposing options. We assessed the associations between genetically predicted protein levels and COVID-19 severity. Leveraging data from the COVID-19 Host Genetics Initiative comparing 6492 hospitalized COVID-19 patients and 1 012 809 controls, we identified 18 proteins with genetically predicted levels to be associated with COVID-19 severity at a false discovery rate of &lt;0.05, including 12 that showed an association even after Bonferroni correction. Of the 18 proteins, 6 showed positive associations and 12 showed inverse associations. In conclusion, we identified 18 candidate proteins for COVID-19 severity.

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