88 research outputs found
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Accelerated epigenetic aging in Werner syndrome.
Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0.0072) and intrinsic epigenetic age acceleration (p=0.04), the latter of which is independent of age-related changes in the composition of peripheral blood cells. A multivariate model analysis reveals that WS is associated with an increase in DNA methylation age (on average 6.4 years, p=0.011) even after adjusting for chronological age, gender, and blood cell counts. Further, WS might be associated with a reduction in naĂŻve CD8+ T cells (p=0.025) according to imputed measures of blood cell counts. Overall, this study shows that WS is associated with an increased epigenetic age of blood cells which is independent of changes in blood cell composition. The extent to which this alteration is a cause or effect of WS disease phenotypes remains unknown
Principles of model specification in ANOVA designs
ANOVAâthe workhorse of experimental psychologyâseems well understood in that behavioral sciences have agreed-upon contrasts and reporting conventions. Yet, we argue this consensus hides considerable flaws in common ANOVA procedures, and these flaws become especially salient in the within-subject and mixed-model cases. The main thesis is that these flaws are in model specification. The specifications underlying common use are deficient from a substantive perspective, that is, they do not match reality in behavioral experiments. The problem, in particular, is that specifications rely on coincidental rather than robust statements about reality. We provide specifications that avoid making arguments based on coincidences, and note these Bayes factor model comparisons among these specifications are already convenient in the BayesFactor package. Finally, we argue that model specification necessarily and critically reflects substantive concerns, and, consequently, is ultimately the responsibility of substantive researchers. Source code for this project is at github/PerceptionAndCognitionLab/stat_aov2
The JASP guidelines for conducting and reporting a Bayesian analysis
Despite the increasing popularity of Bayesian inference in empirical research, few practical guidelines provide detailed recommendations for how to apply Bayesian procedures and interpret the results. Here we offer specific guidelines for four different stages of Bayesian statistical reasoning in a research setting: planning the analysis, executing the analysis, interpreting the results, and reporting the results. The guidelines for each stage are illustrated with a running example. Although the guidelines are geared towards analyses performed with the open-source statistical software JASP, most guidelines extend to Bayesian inference in general
Bayes factors for mixed models: A discussion
van Doorn et al. (2021) outlined various questions that arise when conducting Bayesian model comparison for mixed effects models. Seven response articles offered their own perspective on the preferred setup for mixed model comparison, on the most appropriate specification of prior distributions, and on the desirability of default recommendations. This article presents a round-table discussion that aims to clarify outstanding issues, explore common ground, and outline practical considerations for any researcher wishing to conduct a Bayesian mixed effects model comparison
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification
2018 Research & Innovation Day Program
A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1005/thumbnail.jp
Correction to: Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI).
CORRECTION TO: J CARDIOVASC MAGN RESON (2017) 19: 75. DOI: 10.1186/S12968-017-0389-8: In the original publication of this article [1] the "Competing interests" section was incorrect. The original publication stated the following competing interests
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe
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