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Biostatistics

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https://www.readbyqxmd.com/read/28541380/a-fully-bayesian-latent-variable-model-for-integrative-clustering-analysis-of-multi-type-omics-data
#1
Qianxing Mo, Ronglai Shen, Cui Guo, Marina Vannucci, Keith S Chan, Susan G Hilsenbeck
Identification of clinically relevant tumor subtypes and omics signatures is an important task in cancer translational research for precision medicine. Large-scale genomic profiling studies such as The Cancer Genome Atlas (TCGA) Research Network have generated vast amounts of genomic, transcriptomic, epigenomic, and proteomic data. While these studies have provided great resources for researchers to discover clinically relevant tumor subtypes and driver molecular alterations, there are few computationally efficient methods and tools for integrative clustering analysis of these multi-type omics data...
May 24, 2017: Biostatistics
https://www.readbyqxmd.com/read/28525542/semiparametric-model-and-inference-for-spontaneous-abortion-data-with-a-cured-proportion-and-biased-sampling
#2
Jin Piao, Jing Ning, Christina D Chambers, Ronghui Xu
Evaluating and understanding the risk and safety of using medications for autoimmune disease in a woman during her pregnancy will help both clinicians and pregnant women to make better treatment decisions. However, utilizing spontaneous abortion (SAB) data collected in observational studies of pregnancy to derive valid inference poses two major challenges. First, the data from the observational cohort are not random samples of the target population due to the sampling mechanism. Pregnant women with early SAB are more likely to be excluded from the cohort, and there may be substantial differences between the observed SAB time and those in the target population...
May 18, 2017: Biostatistics
https://www.readbyqxmd.com/read/28520903/covariate-adjusted-classification-trees
#3
Josephine K Asafu-Adjei, Allan R Sampson
In studies that compare several diagnostic groups, subjects can be measured on certain features and classification trees can be used to identify which of them best characterize the differences among groups. However, subjects may also be measured on additional covariates whose ability to characterize group differences is not meaningful or of interest, but may still have an impact on the examined features. Therefore, it is important to adjust for the effects of covariates on these features. We present a new semi-parametric approach to adjust for covariate effects when constructing classification trees based on the features of interest that is readily implementable...
May 17, 2017: Biostatistics
https://www.readbyqxmd.com/read/28520893/using-bayesian-modeling-in-frequentist-adaptive-enrichment-designs
#4
Noah Simon, Richard Simon
Our increased understanding of the mechanistic heterogeneity of diseases has pushed the development of targeted therapeutics. We do not expect all patients with a given disease to benefit from a targeted drug; only those in the target population. That is, those with sufficient dysregulation in the biomolecular pathway targeted by treatment. However, due to complexity of the pathway, and/or technical issues with our characterizing assay, it is often hard to characterize the target population until well into large-scale clinical trials...
May 17, 2017: Biostatistics
https://www.readbyqxmd.com/read/28481968/concordance-measure-and-discriminatory-accuracy-in-transformation-cure-models
#5
Yilong Zhang, Yongzhao Shao
Many populations of early-stage cancer patients have non-negligible latent cure fractions that can be modeled using transformation cure models. However, there is a lack of statistical metrics to evaluate prognostic utility of biomarkers in this context due to the challenges associated with unknown cure status and heavy censorship. In this article, we develop general concordance measures as evaluation metrics for the discriminatory accuracy of transformation cure models including the so-called promotion time cure models and mixture cure models...
May 5, 2017: Biostatistics
https://www.readbyqxmd.com/read/28430872/optimal-screening-schedules-for-disease-progression-with-application-to-diabetic-retinopathy
#6
Ionut Bebu, John M Lachin
Clinical management of chronic diseases requires periodic evaluations. Subjects transition between various levels of severity of a disease over time, one of which may trigger an intervention that requires treatment. For example, in diabetic retinopathy, patients with type 1 diabetes are evaluated yearly for either the onset of proliferative diabetic retinopathy (PDR) or clinically significant macular edema (CSME) that would require immediate treatment to preserve vision. Herein, we investigate methods for the selection of personalized cost-effective screening schedules and compare them with a fixed visit schedule (e...
April 20, 2017: Biostatistics
https://www.readbyqxmd.com/read/28419189/propensity-scores-with-misclassified-treatment-assignment-a-likelihood-based-adjustment
#7
Danielle Braun, Malka Gorfine, Giovanni Parmigiani, Nils D Arvold, Francesca Dominici, Corwin Zigler
Propensity score methods are widely used in comparative effectiveness research using claims data. In this context, the inaccuracy of procedural or billing codes in claims data frequently misclassifies patients into treatment groups, that is, the treatment assignment ($T$) is often measured with error. In the context of a validation data where treatment assignment is accurate, we show that misclassification of treatment assignment can impact three distinct stages of a propensity score analysis: (i) propensity score estimation; (ii) propensity score implementation; and (iii) outcome analysis conducted conditional on the estimated propensity score and its implementation...
April 17, 2017: Biostatistics
https://www.readbyqxmd.com/read/28369273/computational-health-economics-for-identification-of-unprofitable-health-care-enrollees
#8
Sherri Rose, Savannah L Bergquist, Timothy J Layton
Health insurers may attempt to design their health plans to attract profitable enrollees while deterring unprofitable ones. Such insurers would not be delivering socially efficient levels of care by providing health plans that maximize societal benefit, but rather intentionally distorting plan benefits to avoid high-cost enrollees, potentially to the detriment of health and efficiency. In this work, we focus on a specific component of health plan design at risk for health insurer distortion in the Health Insurance Marketplaces: the prescription drug formulary...
March 22, 2017: Biostatistics
https://www.readbyqxmd.com/read/28369172/multivariate-t-nonlinear-mixed-models-with-application-to-censored-multi-outcome-aids-studies
#9
Tsung-I Lin, Wan-Lun Wang
In multivariate longitudinal HIV/AIDS studies, multi-outcome repeated measures on each patient over time may contain outliers, and the viral loads are often subject to a upper or lower limit of detection depending on the quantification assays. In this article, we consider an extension of the multivariate nonlinear mixed-effects model by adopting a joint multivariate-$t$ distribution for random effects and within-subject errors and taking the censoring information of multiple responses into account. The proposed model is called the multivariate-$t$ nonlinear mixed-effects model with censored responses (MtNLMMC), allowing for analyzing multi-outcome longitudinal data exhibiting nonlinear growth patterns with censorship and fat-tailed behavior...
March 20, 2017: Biostatistics
https://www.readbyqxmd.com/read/28369228/marginal-likelihood-estimation-of-negative-binomial-parameters-with-applications-to-rna-seq-data
#10
Luis León-Novelo, Claudio Fuentes, Sarah Emerson
RNA-Seq data characteristically exhibits large variances, which need to be appropriately accounted for in any proposed model. We first explore the effects of this variability on the maximum likelihood estimator (MLE) of the dispersion parameter of the negative binomial distribution, and propose instead to use an estimator obtained via maximization of the marginal likelihood in a conjugate Bayesian framework. We show, via simulation studies, that the marginal MLE can better control this variation and produce a more stable and reliable estimator...
March 19, 2017: Biostatistics
https://www.readbyqxmd.com/read/28369170/supervised-multiblock-sparse-multivariable-analysis-with-application-to-multimodal-brain-imaging-genetics
#11
Atsushi Kawaguchi, Fumio Yamashita
This article proposes a procedure for describing the relationship between high-dimensional data sets, such as multimodal brain images and genetic data. We propose a supervised technique to incorporate the clinical outcome to determine a score, which is a linear combination of variables with hieratical structures to multimodalities. This approach is expected to obtain interpretable and predictive scores. The proposed method was applied to a study of Alzheimer's disease (AD). We propose a diagnostic method for AD that involves using whole-brain magnetic resonance imaging (MRI) and positron emission tomography (PET), and we select effective brain regions for the diagnostic probability and investigate the genome-wide association with the regions using single nucleotide polymorphisms (SNPs)...
March 19, 2017: Biostatistics
https://www.readbyqxmd.com/read/28334312/efficient-inference-for-genetic-association-studies-with-multiple-outcomes
#12
Helene Ruffieux, Anthony C Davison, Jorg Hager, Irina Irincheeva
Combined inference for heterogeneous high-dimensional data is critical in modern biology, where clinical and various kinds of molecular data may be available from a single study. Classical genetic association studies regress a single clinical outcome on many genetic variants one by one, but there is an increasing demand for joint analysis of many molecular outcomes and genetic variants in order to unravel functional interactions. Unfortunately, most existing approaches to joint modeling are either too simplistic to be powerful or are impracticable for computational reasons...
March 16, 2017: Biostatistics
https://www.readbyqxmd.com/read/28369188/bayesian-inference-for-causal-mechanisms-with-application-to-a-randomized-study-for-postoperative-pain-control
#13
Michela Baccini, Alessandra Mattei, Fabrizia Mealli
We conduct principal stratification and mediation analysis to investigate to what extent the positive overall effect of treatment on postoperative pain control is mediated by postoperative self administration of intra-venous analgesia by patients in a prospective, randomized, double-blind study. Using the Bayesian approach for inference, we estimate both associative and dissociative principal strata effects arising in principal stratification, as well as natural effects from mediation analysis. We highlight that principal stratification and mediation analysis focus on different causal estimands, answer different causal questions, and involve different sets of structural assumptions...
March 15, 2017: Biostatistics
https://www.readbyqxmd.com/read/28334305/variance-component-score-test-for-time-course-gene-set-analysis-of-longitudinal-rna-seq-data
#14
Denis Agniel, Boris P Hejblum
As gene expression measurement technology is shifting from microarrays to sequencing, the statistical tools available for their analysis must be adapted since RNA-seq data are measured as counts. It has been proposed to model RNA-seq counts as continuous variables using nonparametric regression to account for their inherent heteroscedasticity. In this vein, we propose tcgsaseq, a principled, model-free, and efficient method for detecting longitudinal changes in RNA-seq gene sets defined a priori. The method identifies those gene sets whose expression varies over time, based on an original variance component score test accounting for both covariates and heteroscedasticity without assuming any specific parametric distribution for the (transformed) counts...
March 10, 2017: Biostatistics
https://www.readbyqxmd.com/read/28334261/penalized-likelihood-estimation-of-a-trivariate-additive-probit-model
#15
Panagiota Filippou, Giampiero Marra, Rosalba Radice
This article proposes a penalized likelihood method to estimate a trivariate probit model, which accounts for several types of covariate effects (such as linear, nonlinear, random, and spatial effects), as well as error correlations. The proposed approach also addresses the difficulty in estimating accurately the correlation coefficients, which characterize the dependence of binary responses conditional on covariates. The parameters of the model are estimated within a penalized likelihood framework based on a carefully structured trust region algorithm with integrated automatic multiple smoothing parameter selection...
March 4, 2017: Biostatistics
https://www.readbyqxmd.com/read/28334230/guided-bayesian-imputation-to-adjust-for-confounding-when-combining-heterogeneous-data-sources-in-comparative-effectiveness-research
#16
Joseph Antonelli, Corwin Zigler, Francesca Dominici
In comparative effectiveness research, we are often interested in the estimation of an average causal effect from large observational data (the main study). Often this data does not measure all the necessary confounders. In many occasions, an extensive set of additional covariates is measured for a smaller and non-representative population (the validation study). In this setting, standard approaches for missing data imputation might not be adequate due to the large number of missing covariates in the main data relative to the smaller sample size of the validation data...
March 3, 2017: Biostatistics
https://www.readbyqxmd.com/read/28375451/multivariate-semiparametric-spatial-methods-for-imaging-data
#17
Huaihou Chen, Guanqun Cao, Ronald A Cohen
Univariate semiparametric methods are often used in modeling nonlinear age trajectories for imaging data, which may result in efficiency loss and lower power for identifying important age-related effects that exist in the data. As observed in multiple neuroimaging studies, age trajectories show similar nonlinear patterns for the left and right corresponding regions and for the different parts of a big organ such as the corpus callosum. To incorporate the spatial similarity information without assuming spatial smoothness, we propose a multivariate semiparametric regression model with a spatial similarity penalty, which constrains the variation of the age trajectories among similar regions...
April 1, 2017: Biostatistics
https://www.readbyqxmd.com/read/28025183/inequality-in-treatment-benefits-can-we-determine-if-a-new-treatment-benefits-the-many-or-the-few
#18
Emily J Huang, Ethan X Fang, Daniel F Hanley, Michael Rosenblum
In many randomized controlled trials, the primary analysis focuses on the average treatment effect and does not address whether treatment benefits are widespread or limited to a select few. This problem affects many disease areas, since it stems from how randomized trials, often the gold standard for evaluating treatments, are designed and analyzed. Our goal is to learn about the fraction who benefit from a new treatment using randomized trial data. We consider the case where the outcome is ordinal, with binary outcomes as a special case...
April 1, 2017: Biostatistics
https://www.readbyqxmd.com/read/28025182/incorporating-social-contact-data-in-spatio-temporal-models-for-infectious-disease-spread
#19
Sebastian Meyer, Leonhard Held
Routine public health surveillance of notifiable infectious diseases gives rise to weekly counts of reported cases-possibly stratified by region and/or age group. We investigate how an age-structured social contact matrix can be incorporated into a spatio-temporal endemic-epidemic model for infectious disease counts. To illustrate the approach, we analyze the spread of norovirus gastroenteritis over six age groups within the 12 districts of Berlin, 2011-2015, using contact data from the POLYMOD study. The proposed age-structured model outperforms alternative scenarios with homogeneous or no mixing between age groups...
April 1, 2017: Biostatistics
https://www.readbyqxmd.com/read/28025181/a-rigorous-statistical-framework-for-spatio-temporal-pollution-prediction-and-estimation-of-its-long-term-impact-on-health
#20
Duncan Lee, Sabyasachi Mukhopadhyay, Alastair Rushworth, Sujit K Sahu
In the United Kingdom, air pollution is linked to around 40000 premature deaths each year, but estimating its health effects is challenging in a spatio-temporal study. The challenges include spatial misalignment between the pollution and disease data; uncertainty in the estimated pollution surface; and complex residual spatio-temporal autocorrelation in the disease data. This article develops a two-stage model that addresses these issues. The first stage is a spatio-temporal fusion model linking modeled and measured pollution data, while the second stage links these predictions to the disease data...
April 1, 2017: Biostatistics
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