scholarly journals Meta-analysis of Cytometry Data Reveals Racial Differences in Immune Cells

2017 ◽  
Author(s):  
Zicheng Hu ◽  
Chethan Jujjavarapu ◽  
Jacob J. Hughey ◽  
Sandra Andorf ◽  
Hao-Chih Lee ◽  
...  
Keyword(s):  
Racial Differences ◽  
Immune Cells ◽  
Statistical Power ◽  
Meta Analysis ◽  
Cell Populations ◽  
Clustering Methods ◽  
Mass Cytometry ◽  
Scanning Method ◽  
The Public ◽  
Multiple Cell

AbstractWhile meta-analysis has demonstrated increased statistical power and more robust estimations in studies, the application of this commonly accepted methodology to cytometry data has been challenging. Different cytometry studies often involve diverse sets of markers. Moreover, the detected values of the same marker are inconsistent between studies due to different experimental designs and cytometer configurations. As a result, the cell subsets identified by existing auto-gating methods cannot be directly compared across studies. We developed MetaCyto for automated meta-analysis of both flow and mass cytometry (CyTOF) data. By combining clustering methods with a silhouette scanning method, MetaCyto is able to identify commonly labeled cell subsets across studies, thus enabling meta-analysis. Applying MetaCyto across a set of 10 heterogeneous cytometry studies totaling 2926 samples enabled us to identify multiple cell populations exhibiting differences in abundance between White and Asian adults. Software is released to the public through GitHub (github.com/hzc363/MetaCyto).

scholarly journals Comparison of Clustering Methods for High-Dimensional Single-Cell Flow and Mass Cytometry Data

2016 ◽  
Author(s):  
Lukas M. Weber ◽  
Mark D. Robinson
Keyword(s):  
High Dimensional Data ◽  
High Dimensional ◽  
Cell Populations ◽  
Data Sets ◽  
Protein Markers ◽  
Clustering Methods ◽  
Mass Cytometry ◽  
Desktop Computer ◽  
Dimensional Flow ◽  
Clustering Comparison

AbstractRecent technological developments in high-dimensional flow cytometry and mass cytometry (CyTOF) have made it possible to detect expression levels of dozens of protein markers in thousands of cells per second, allowing cell populations to be characterized in unprecedented detail. Traditional data analysis by “manual gating” can be inefficient and unreliable in these high-dimensional settings, which has led to the development of a large number of automated analysis methods. Methods designed for unsupervised analysis use specialized clustering algorithms to detect and define cell populations for further downstream analysis. Here, we have performed an up-to-date, extensible performance comparison of clustering methods for high-dimensional flow and mass cytometry data. We evaluated methods using several publicly available data sets from experiments in immunology, containing both major and rare cell populations, with cell population identities from expert manual gating as the reference standard. Several methods performed well, including FlowSOM, X-shift, PhenoGraph, Rclusterpp, and flowMeans. Among these, FlowSOM had extremely fast runtimes, making this method well-suited for interactive, exploratory analysis of large, high-dimensional data sets on a standard laptop or desktop computer. These results extend previously published comparisons by focusing on high-dimensional data and including new methods developed for CyTOF data. R scripts to reproduce all analyses are available from GitHub (https://github.com/lmweber/cytometry-clustering-comparison), and pre-processed data files are available from FlowRepository (FR-FCM-ZZPH), allowing our comparisons to be extended to include new clustering methods and reference data sets.

scholarly journals Tissue Infiltrating Immune Cells as Prognostic Biomarkers in Endometrial Cancer: A Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fang Guo ◽  
Yishan Dong ◽  
Qingqing Tan ◽  
Jing Kong ◽  
Bin Yu
Keyword(s):  
Endometrial Cancer ◽  
T Cell ◽  
Cell Density ◽  
Immune Cells ◽  
Statistical Power ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Gynecology And Obstetrics ◽  
The Relationship

Background. The association between tumour-infiltrating immune cells and the prognosis of endometrial cancer (EC) is controversial due to the smaller sample sizes and limited statistical power of the extant studies. We carried out a meta-analysis of the relationship between tumour-infiltrating immune cells and EC survival outcomes. Methods. A literature search in multiple databases was carried out up to December 2019. Pooled hazard ratio (HRs) and 95% confidence intervals (CIs) were calculated by the Z-test to assess the association between infiltrating immune cells and overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), disease-specific survival (DSS), and disease-free survival (DFS). A subgroup analysis was performed based on the localisation of immune cells in tumour parenchyma or stroma, immune markers, and the International Federation of Gynecology and Obstetrics stage. Heterogeneity and publication bias between studies were evaluated by Cochran’s Q-test and Egger regression test, respectively. Results. Seventeen studies were included in the analysis. The pooled HR of OS, PFS, DSS, and DFS indicated that a high CD8+ T cell density was associated with a favorable prognosis in EC patients. A significant relationship was found between a high density of CD45RO+ T cells and a favorable OS in EC patients, but the FoxP3+ T cell density was not associated with either OS or RFS. A high TAM density was associated with a worse PFS. However, a sensitivity analysis indicated that the findings of PFS and DSS in CD8+ T cell and PFS in TAM were not robust results. Conclusion. This is the first meta-analysis of the relationship between tumour-infiltrating immune cells and the prognosis of EC. High CD8+ and CD45RO+ T cell densities in tumours were associated with favorable outcomes in EC patients.

scholarly journals Mass Cytometry Analysis of Dysregulated Cytokine Production and Intracellular Signaling in Myelofibrosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4277-4277 ◽  
Author(s):  
Daniel A.C. Fisher ◽  
Cathrine A. Miner ◽  
Elizabeth K. Engle ◽  
Taylor M. Brost ◽  
Olga Malkova ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Cytokine Production ◽  
Jak2 V617f ◽  
Cell Populations ◽  
Mass Cytometry ◽  
Advisory Committees ◽  
Downstream Signaling ◽  
Cd34 Cells ◽  
Multiple Cell

Abstract Myeloproliferative neoplasms including myelofibrosis (MF) are characterized by a malignant clone containing JAK2 V617F or other mutations leading to unregulated JAK2 kinase activity. MF is characterized by anemia, splenomegaly, bone marrow fibrosis, inflammatory cytokine production, and a propensity for transformation to secondary acute myeloid leukemia. Inhibition of JAK2 with ruxolitinib improves constitutional symptoms and splenomegaly and lowers circulating plasma cytokine levels. However, improvements in anemia, fibrosis, and malignant clonal burden are infrequent. These observations illustrate the need for improved therapy for MF. The objective of this study is to better understand the relationship between dysregulated cytokines and downstream signaling in MF, with the goal of determining how these pathways can be more effectively manipulated for therapeutic benefit. To interrogate altered signaling in MF, we have employed mass cytometry (CyTOF), a method which enables the quantitative analysis of signaling throughout hematopoiesis. In our survey of signaling in MF, hyperactivation of the NFκB signaling pathway was found to be widespread. This finding was corroborated by gene set enrichment analysis (GSEA) of a published gene expression dataset of CD34+ cells from MF versus normal controls (Norfo et al. 2014 Blood). Evidence for NFκB hyperactivation, both by mass cytometry and GSEA, was strongest in JAK2V617F-mutant MF patients. This supports a hypothesis that pronounced NFκB signaling hyperactivation is a consequence of mutant JAK2. In MF, hyperactivated NFκB signaling was widespread among hematopoietic cell populations, including T cells. This distribution suggests that NFκB activation may be partly driven by non-cell-autonomous mechanisms. Consistent with previous studies, plasma TNFα levels were found to be elevated in these patients, suggesting that excessive production of TNFα could result in downstream activation of NFκB across multiple cell populations in a non-cell-autonomous fashion. To further elucidate the etiology of systemic NFκB hyperactivation and understand the interplay of inflammatory cytokines and downstream signaling, we extended our mass cytometry approach to study the cellular distribution of cytokine production in MF. A panel of 22 surface marker antibodies and 12 cytokine antibodies was developed for these experiments. Examination of peripheral blood from two JAK2V617F-mutant MF patients revealed that intracellular levels of several cytokines were constitutively elevated in both MF patients compared to healthy controls. Monocytes produced the highest levels of TNFα among hematopoietic populations, and these were higher in MF versus control monocytes. Supranormal cytokine expression was accentuated by stimulation with PMA/ionomycin or TLR ligands R848 or PAM3CSK4. Incubation with TNFα led to supranormal levels of the cytokines MIP1β and IL-6, in monocytes from one or both patients. Therefore, abnormal production of TNFα by MF patient monocytes could result in overproduction of IL-6, and MIP1β in the same cells. PMA/ionomycin led to above normal production of TNFα from MF Lin-CD34+ cells and CD33+CD34- immature myeloid cells, suggestive that these cells could be hypersensitive to pathophysiologic signaling stimulations in a manner resulting in elevated cytokine production. MF patient T cells also showed hypersensitivity to PMA/ionomycin stimulation, compared with controls, in their production of IFNγ and MIP1β. These cytokines, along with the MF monocyte-overexpressed cytokines TNFα, IL-6, and MIP1β, were found to be elevated in MF patient plasma, consistent with prior studies. These findings imply that multiple cell populations in JAK2 V617F-mutant MF patients overexpress inflammatory cytokines and are hypersensitive to inflammatory insults. The upregulation of cytokines is likely to underlie the systemic hyperactivation of NFκB signaling observed in MF, and could generate non-cell-autonomous effects on the malignant myeloid clone. While NFκB phosphorylation responses to TNFα appear strongest in Lin-CD34+ cells, other cytokines may mediate signaling abnormalities across a variety of cell types. Future experiments will attempt to identify signaling effects of multiple elevated cytokines, which may underlie features of MF that persist despite JAK2 inhibitor therapy. Disclosures Oh: CTI: Research Funding; Janssen: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Power-Enhanced Funnel Plots for Meta-Analysis

2020 ◽  
Vol 228 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Michael Kossmeier ◽  
Ulrich S. Tran ◽  
Martin Voracek
Keyword(s):  
Statistical Power ◽  
Meta Analysis ◽  
Relevant Information ◽  
Selective Reporting ◽  
Graphical Display ◽  
Funnel Plot ◽  
Evidential Value ◽  
Graphical Displays ◽  
Funnel Plots ◽  
Meta Analyses

Abstract. Currently, dedicated graphical displays to depict study-level statistical power in the context of meta-analysis are unavailable. Here, we introduce the sunset (power-enhanced) funnel plot to visualize this relevant information for assessing the credibility, or evidential value, of a set of studies. The sunset funnel plot highlights the statistical power of primary studies to detect an underlying true effect of interest in the well-known funnel display with color-coded power regions and a second power axis. This graphical display allows meta-analysts to incorporate power considerations into classic funnel plot assessments of small-study effects. Nominally significant, but low-powered, studies might be seen as less credible and as more likely being affected by selective reporting. We exemplify the application of the sunset funnel plot with two published meta-analyses from medicine and psychology. Software to create this variation of the funnel plot is provided via a tailored R function. In conclusion, the sunset (power-enhanced) funnel plot is a novel and useful graphical display to critically examine and to present study-level power in the context of meta-analysis.

Replication of the Superstition and Performance Study by

2014 ◽  
Vol 45 (3) ◽  
pp. 239-245 ◽  
Author(s):  
Robert J. Calin-Jageman ◽  
Tracy L. Caldwell
Keyword(s):  
Task Difficulty ◽  
Statistical Power ◽  
Meta Analysis ◽  
A Priori ◽  
Significant Heterogeneity ◽  
Performance Study ◽  
Improve Performance ◽  
Research Designs ◽  
Series Of Experiments ◽  
And Performance

A recent series of experiments suggests that fostering superstitions can substantially improve performance on a variety of motor and cognitive tasks ( Damisch, Stoberock, & Mussweiler, 2010 ). We conducted two high-powered and precise replications of one of these experiments, examining if telling participants they had a lucky golf ball could improve their performance on a 10-shot golf task relative to controls. We found that the effect of superstition on performance is elusive: Participants told they had a lucky ball performed almost identically to controls. Our failure to replicate the target study was not due to lack of impact, lack of statistical power, differences in task difficulty, nor differences in participant belief in luck. A meta-analysis indicates significant heterogeneity in the effect of superstition on performance. This could be due to an unknown moderator, but no effect was observed among the studies with the strongest research designs (e.g., high power, a priori sampling plan).

Statistical Power in Meta-Analysis

2006 ◽  
Author(s):  
Guy Cafri ◽  
Michael T. Brannick ◽  
Jeffrey Kromrey
Keyword(s):  
Statistical Power ◽  
Meta Analysis

scholarly journals A Model-Based Meta-Analysis of Willingness to Participate in Cancer Screening

2021 ◽  
Vol 18 (5) ◽  
pp. 2580
Author(s):  
Guangchao Charles Feng ◽  
Zhiliang Lin ◽  
Wanhua Ou ◽  
Xianglin Su ◽  
Qing Yan
Keyword(s):  
Structural Equation ◽  
Meta Analysis ◽  
Health Belief ◽  
Screening Tests ◽  
Equation Modeling ◽  
Willingness To Participate ◽  
Early Screening ◽  
The Public ◽  
Screening Programs ◽  
Belief Model

Although early screening tests are beneficial for the detection and treatment of cancers, many people have failed to participate in screening tests. The present study aims to explore the theoretical underpinning of low participation in screening programs using the method of meta-analytic structural equation modeling. It was found that the health belief model is the most adopted theoretical framework. Moreover, the intended uptake of screening was positively predicted only by cues to action, health literacy, and perceived susceptibility. As a result, a health intention model, including the three significant variables, is proposed. The practical implications of the findings are that health communication campaigns should focus on enlightening and engaging the public through all necessary means to raise awareness and transfer knowledge in relation to screening procedures as well as cancers per se.

scholarly journals POS1097 TREATMENT KNOWLEDGE AND PREFERENCES FOR BLACK PEOPLE WITH HIP AND KNEE OSTEOARTHRITIS: A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 828.2-829
Author(s):  
C. Brantner ◽  
D. Pearce-Fisher ◽  
C. Moezinia ◽  
H. Tornberg ◽  
J. Fitzgerald ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Racial Differences ◽  
Black People ◽  
Meta Analysis ◽  
Treatment Options ◽  
Cochrane Library ◽  
Treatment Preferences ◽  
White People ◽  
Narcotic Analgesics ◽  
Accessible Information

Background:Black people are less likely to undergo total joint arthroplasties, despite reporting more severe symptoms. (1) While racial disparities exist in treatment utilization for osteoarthritis, comprehensive studies of the treatment preferences of Black people have not been conducted.Objectives:The purpose of this manuscript is to systematically review the literature and identify Black osteoarthritis patients’ treatment preferences to understand how they may contribute to racial differences in the utilization of different treatment options.Methods:Searches ran on April 8, 2019 and April 7, 2020 in the following databases: Ovid MEDLINE (ALL - 1946 to Present); Ovid EMBASE (1974 to present); and The Cochrane Library (Wiley). Using the Patient/Population-Intervention-Comparison/Comparator-Outcome (PICO) format, our population of interest was Black people with hip and/or knee osteoarthritis, our intervention was preferences and opinions about treatment options for osteoarthritis, our comparator was white people with hip and/or knee osteoarthritis, and our outcome was preferences of osteoarthritis therapies. The protocol was registered under the PROSPERO international register, and the Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed.Results:Searches across the chosen databases retrieved 10,894 studies after de-duplication, 182 full text, and 31 selected for inclusion in this review. Black people were less likely to use NSAIDs or narcotic analgesics compared to white people. (Figure 1) Black people were more likely than white people to use spirituality and prayer, as well as topical treatments. Utilization of meditation, supplement/vitamin use, and hot/cold treatments was not significantly different between groups. Black people were less willing than white people to consider or undergo joint replacements, even if the procedure was needed and recommended by a physician.Conclusion:Racial differences persist in OA care across the spectrum of options. Future interventions should focus on providing accessible information surrounding treatment options and targeting perceptions of the importance of joint health.References:[1]Suarez-Almazor ME, Souchek J, Kelly PA, et al. Ethnic Variation in Knee Replacement: Patient Preferences or Uninformed Disparity? Arch Intern Med. 2005;165(10):1117-1124. doi:10.1001/archinte.165.10.1117Figure 1.Meta-analysis describing the odds ratios of Black people using NSAIDs and Narcotic Analgesics compared to white peopleDisclosure of Interests:Collin Brantner: None declared, Diyu Pearce-Fisher: None declared, Carine Moezinia: None declared, Haley Tornberg: None declared, John FitzGerald: None declared, Michael Parks Consultant of: Zimmer Biomet, Peter Sculco Consultant of: EOS Imaging, Intellijoint Surgical, DePuy Synthes, Lima Corporate, Cynthia Kahlenberg: None declared, Curtis Mensah: None declared, Ajay Premkuar: None declared, Nicholas Williams: None declared, Michelle Demetres: None declared, Susan Goodman Consultant of: UCB, Grant/research support from: Novartis, Horizon Therapeutics.

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