356 research outputs found
On estimation of covariance function for functional data with detection limits
In many studies on disease progression, biomarkers are restricted by detection limits, hence informatively missing. Current approaches ignore the problem by just filling in the value of the detection limit for the missing observations for the estimation of the mean and covariance function, which yield inaccurate estimation. Inspired by our recent work [Liu and Houwing-Duistermaat (2022), āFast Estimators for the Mean Function for Functional Data with Detection Limitsā, Stat, e467.] in which novel estimators for mean function for data subject to detection limit are proposed, in this paper, we will propose a novel estimator for the covariance function for sparse and dense data subject to a detection limit. We will derive the asymptotic properties of the estimator. We will compare our method to the standard method, which ignores the detection limit, via simulations. We will illustrate the new approach by analysing biomarker data subject to a detection limit. In contrast to the standard method, our method appeared to provide more accurate estimates of the covariance. Moreover its computation time is small
Combining evidence for association from transmission disequilibrium and case-control studies using single-nucleotide polymorphisms
The aim of the present analysis is to combine evidence for association from the two most commonly used designs in genetic association analysis, the case-control design and the transmission disequilibrium test (TDT) design. The cases here are affected offspring from nuclear families and are used in both the case-control and TDT designs. As a result, inference from these designs is not independent. We applied a simple logistic regression method for combining evidence for association from case-control and TDT designs to single-nucleotide polymorphism data purchased on a region on chromosome 3, replicate 1 of the Aipotu population. Combining the evidence from the case-control and TDT designs yielded a 5ā10% reduction in the standard errors of the relative risk estimates. The authors did not know the results before the analyses were conducted
Methods to test for association between a disease and a multi-allelic marker applied to a candidate region
We report the analysis results of the Genetic Analysis Workshop 14 simulated microsatellite marker dataset, using replicate 50 from the Danacaa population. We applied several methods for association analysis of multi-allelic markers to case-control data to study the association between Kofendrerd Personality Disorder and multi-allelic markers in a candidate region previously identified by the linkage analysis. Evidence for association was found for marker D03S0127 (p < 0.01). The analyses were done without any prior knowledge of the answers
Survival analysis with delayed entry in selected families with application to human longevity
In the field of aging research, family-based sampling study designs are commonly used to study the lifespans of long-lived family members. However, the specific sampling procedure should be carefully taken into account in order to avoid biases. This work is motivated by the Leiden Longevity Study, a family-based cohort of long-lived siblings. Families were invited to participate in the study if at least two siblings were ālong-livedā, where ālong-livedā meant being older than 89 years for men or older than 91 years for women. As a result, more than 400 families were included in the study and followed for around 10 years. For estimation of marker-specific survival probabilities and correlations among life times of family members, delayed entry due to outcome-dependent sampling mechanisms has to be taken into account. We consider shared frailty models to model left-truncated correlated survival data. The treatment of left truncation in shared frailty models is still an open issue and the literature on this topic is scarce. We show that the current approaches provide, in general, biased estimates and we propose a new method to tackle this selection problem by applying a correction on the likelihood estimation by means of inverse probability weighting at the family level
Does pathway analysis make it easier for common variants to tag rare ones?
Analyzing sequencing data is difficult because of the low frequency of rare variants, which may result in low power to detect associations. We consider pathway analysis to detect multiple common and rare variants jointly and to investigate whether analysis at the pathway level provides an alternative strategy for identifying susceptibility genes. Available pathway analysis methods for data from genome-wide association studies might not be efficient because these methods are designed to detect common variants. Here, we investigate the performance of several existing pathway analysis methods for sequencing data. In particular, we consider the global test, which does not consider linkage disequilibrium between the variants in a gene. We improve the performance of the global test by assigning larger weights to rare variants, as proposed in the weighted-sum approach. Our conclusion is that straightforward application of pathway analysis is not satisfactory; hence, when common and rare variants are jointly analyzed, larger weights should be assigned to rare variants
Discussion on the paper āStatistical contributions to bioinformatics: Design, modelling, structure learning and integrationā by Jeffrey S. Morris and Veerabhadran Baladandayuthapani
Bioinformatics is an important research area for statisticians. This discussion provides some additional topics to the paper, namely on statistical contributions to detect differential expressed genes, for protein structure prediction, and for the analysis of highly correlated features in Glycomics datasets
On Estimation of the Effect Lag of Predictors and Prediction in a Functional Linear Model
We propose a functional linear model to predict a functional response using multiple functional and longitudinal predictors and to estimate the effect lags of predictors. The coefficient functions are written as the expansion of a basis system (e.g. functional principal components, splines), and the coefficients of the basis functions are estimated via optimizing a penalization criterion. Then effect lags are determined by simultaneously searching on a prior designed grid mesh based on minimization of a proposed prediction error criterion. Mathematical properties of the estimated regression functions and predicted responses are studied. The performance of the method is evaluated by extensive simulations and a real data analysis application on chronic obstructive pulmonary disease (COPD)
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