Combining multiple biomarker models in logistic regression.
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PROVIDER: S-EPMC7092376 | BioStudies |
REPOSITORIES: biostudies
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Project description:<h4>Background</h4>The main problem in many model-building situations is to choose from a large set of covariates those that should be included in the "best" model. A decision to keep a variable in the model might be based on the clinical or statistical significance. There are several variable selection algorithms in existence. Those methods are mechanical and as such carry some limitations. Hosmer and Lemeshow describe a purposeful selection of covariates within which an analyst makes a variable selection decision at each step of the modeling process.<h4>Methods</h4>In this paper we introduce an algorithm which automates that process. We conduct a simulation study to compare the performance of this algorithm with three well documented variable selection procedures in SAS PROC LOGISTIC: FORWARD, BACKWARD, and STEPWISE.<h4>Results</h4>We show that the advantage of this approach is when the analyst is interested in risk factor modeling and not just prediction. In addition to significant covariates, this variable selection procedure has the capability of retaining important confounding variables, resulting potentially in a slightly richer model. Application of the macro is further illustrated with the Hosmer and Lemeshow Worchester Heart Attack Study (WHAS) data.<h4>Conclusion</h4>If an analyst is in need of an algorithm that will help guide the retention of significant covariates as well as confounding ones they should consider this macro as an alternative tool.
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Project description:<b>Background:</b> The fecal immunochemical test (FIT) is a widely used strategy for colorectal cancer (CRC) screening with moderate sensitivity. To further increase the sensitivity of FIT in identifying colorectal neoplasia, in this study, we established a classifier model by combining FIT result and other demographic and clinical features. <b>Methods:</b> A total of 4,477 participants were examined with FIT and those who tested positive (over 100 ng/ml) were followed up by a colonoscopy examination. Demographic and clinical information of participants including four domains (basic information, clinical history, diet habits and life styles) that consist of 15 features were retrieved from questionnaire surveys. A mean decrease accuracy (MDA) score was used to select features that are mostly related to CRC. Five different algorithms including logistic regression (LR), classification and regression tree (CART), support vector machine (SVM), artificial neural network (ANN) and random forest (RF) were used to generate a classifier model, through a 10X cross validation process. Area under curve (AUC) and normalized mean squared error (NMSE) were used in the evaluation of the performance of the model. <b>Results:</b> The top six features that are mostly related to CRC include age, gender, history of intestinal adenoma or polyposis, smoking history, gastrointestinal discomfort symptom and fruit eating habit were selected. LR algorithm was used in the generation of the model. An AUC score of 0.92 and an NMSE score of 0.076 were obtained by the final classifier model in separating normal individuals from participants with colorectal neoplasia. <b>Conclusion:</b> Our results provide a new "Funnel" strategy in colorectal neoplasia screening via adding a classifier model filtering step between FIT and colonoscopy examination. This strategy minimizes the need of colonoscopy examination while increases the sensitivity of FIT-based CRC screening.
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Project description:Propensity score methods, such as subclassification, are a common approach to control for confounding when estimating causal effects in non-randomized studies. Propensity score subclassification groups individuals into subclasses based on their propensity score values. Effect estimates are obtained within each subclass and then combined by weighting by the proportion of observations in each subclass. Combining subclass-specific estimates by weighting by the inverse variance is a promising alternative approach; a similar strategy is used in meta-analysis for its efficiency. We use simulation to compare performance of each of the two methods while varying (i) the number of subclasses, (ii) extent of propensity score overlap between the treatment and control groups (i.e., positivity), (iii) incorporation of survey weighting, and (iv) presence of heterogeneous treatment effects across subclasses. Both methods perform well in the absence of positivity violations and with a constant treatment effect with weighting by the inverse variance performing slightly better. Weighting by the proportion in subclass performs better in the presence of heterogeneous treatment effects across subclasses. We apply these methods to an illustrative example estimating the effect of living in a disadvantaged neighborhood on risk of past-year anxiety and depressive disorders among U.S. urban adolescents. This example entails practical positivity violations but no evidence of treatment effect heterogeneity. In this case, weighting by the inverse variance when combining across propensity score subclasses results in more efficient estimates that ultimately change inference. Copyright © 2016 John Wiley & Sons, Ltd.
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Project description:We derive an algorithm to directly solve logistic regression based on cardinality constraint, group sparsity and use it to classify intra-subject MRI sequences (e.g. cine MRIs) of healthy from diseased subjects. Group cardinality constraint models are often applied to medical images in order to avoid overfitting of the classifier to the training data. Solutions within these models are generally determined by relaxing the cardinality constraint to a weighted feature selection scheme. However, these solutions relate to the original sparse problem only under specific assumptions, which generally do not hold for medical image applications. In addition, inferring clinical meaning from features weighted by a classifier is an ongoing topic of discussion. Avoiding weighing features, we propose to directly solve the group cardinality constraint logistic regression problem by generalizing the Penalty Decomposition method. To do so, we assume that an intra-subject series of images represents repeated samples of the same disease patterns. We model this assumption by combining series of measurements created by a feature across time into a single group. Our algorithm then derives a solution within that model by decoupling the minimization of the logistic regression function from enforcing the group sparsity constraint. The minimum to the smooth and convex logistic regression problem is determined via gradient descent while we derive a closed form solution for finding a sparse approximation of that minimum. We apply our method to cine MRI of 38 healthy controls and 44 adult patients that received reconstructive surgery of Tetralogy of Fallot (TOF) during infancy. Our method correctly identifies regions impacted by TOF and generally obtains statistically significant higher classification accuracy than alternative solutions to this model, i.e., ones relaxing group cardinality constraints.
2017-01-01 | S-EPMC5099121 | BioStudies
Project description:<h4>Background</h4>Selecting genes and pathways indicative of disease is a central problem in computational biology. This problem is especially challenging when parsing multi-dimensional genomic data. A number of tools, such as L1-norm based regularization and its extensions elastic net and fused lasso, have been introduced to deal with this challenge. However, these approaches tend to ignore the vast amount of a priori biological network information curated in the literature.<h4>Results</h4>We propose the use of graph Laplacian regularized logistic regression to integrate biological networks into disease classification and pathway association problems. Simulation studies demonstrate that the performance of the proposed algorithm is superior to elastic net and lasso analyses. Utility of this algorithm is also validated by its ability to reliably differentiate breast cancer subtypes using a large breast cancer dataset recently generated by the Cancer Genome Atlas (TCGA) consortium. Many of the protein-protein interaction modules identified by our approach are further supported by evidence published in the literature. Source code of the proposed algorithm is freely available at http://www.github.com/zhandong/Logit-Lapnet.<h4>Conclusion</h4>Logistic regression with graph Laplacian regularization is an effective algorithm for identifying key pathways and modules associated with disease subtypes. With the rapid expansion of our knowledge of biological regulatory networks, this approach will become more accurate and increasingly useful for mining transcriptomic, epi-genomic, and other types of genome wide association studies.
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Project description:Statistical power to detect disease variants can be increased by weighting candidates by their evidence of natural selection. To demonstrate that this theoretical idea works in practice, we performed an association study of 10 putative resistance variants in 471 severe malaria cases and 474 controls from the Luo in Kenya. We replicated associations at HBB (P=.0008) and CD36 (P=.03) but also showed that the same variants are unusually differentiated in frequency between the Luo and Yoruba (who historically have been exposed to malaria) and the Masai and Kikuyu (who have not been exposed). This empirically demonstrates that combining association analysis with evidence of natural selection can increase power to detect risk variants by orders of magnitude--up to P=.000018 for HBB and P=.00043 for CD36.
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Project description:The four-parameter logistic (4PL) model has recently attracted much interest in educational testing and psychological measurement. This paper develops a new Gibbs-slice sampling algorithm for estimating the 4PL model parameters in a fully Bayesian framework. Here, the Gibbs algorithm is employed to improve the sampling efficiency by using the conjugate prior distributions in updating asymptote parameters. A slice sampling algorithm is used to update the 2PL model parameters, which overcomes the dependence of the Metropolis–Hastings algorithm on the proposal distribution (tuning parameters). In fact, the Gibbs-slice sampling algorithm not only improves the accuracy of parameter estimation, but also enhances sampling efficiency. Simulation studies are conducted to show the good performance of the proposed Gibbs-slice sampling algorithm and to investigate the impact of different choices of prior distribution on the accuracy of parameter estimation. Based on Markov chain Monte Carlo samples from the posterior distributions, the deviance information criterion and the logarithm of the pseudomarginal likelihood are considered to assess the model fittings. Moreover, a detailed analysis of PISA data is carried out to illustrate the proposed methodology.
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Project description:Combining multiple markers can improve classification accuracy compared with using a single marker. In practice, covariates associated with markers or disease outcome can affect the performance of a biomarker or biomarker combination in the population. The covariate-adjusted receiver operating characteristic (ROC) curve has been proposed as a tool to tease out the covariate effect in the evaluation of a single marker; this curve characterizes the classification accuracy solely because of the marker of interest. However, research on the effect of covariates on the performance of marker combinations and on how to adjust for the covariate effect when combining markers is still lacking. In this article, we examine the effect of covariates on classification performance of linear marker combinations and propose to adjust for covariates in combining markers by maximizing the nonparametric estimate of the area under the covariate-adjusted ROC curve. The proposed method provides a way to estimate the best linear biomarker combination that is robust to risk model assumptions underlying alternative regression-model-based methods. The proposed estimator is shown to be consistent and asymptotically normally distributed. We conduct simulations to evaluate the performance of our estimator in cohort and case/control designs and compare several different weighting strategies during estimation with respect to efficiency. Our estimator is also compared with alternative regression-model-based estimators or estimators that maximize the empirical area under the ROC curve, with respect to bias and efficiency. We apply the proposed method to a biomarker study from an human immunodeficiency virus vaccine trial. Copyright © 2017 John Wiley & Sons, Ltd.
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Project description:Because of the limited information from the GAW20 samples when only case-control or trio data are considered, we propose eLBL, an extension of the Logistic Bayesian LASSO (least absolute shrinkage and selection operator) methodology so that both types of data can be analyzed jointly in the hope of obtaining an increased statistical power, especially for detecting association between rare haplotypes and complex diseases. The methodology is further extended to account for familial correlation among the case-control individuals and the trios. A 2-step analysis strategy was taken to first perform a genome-wise single single-nucleotide polymorphism (SNP) search using the Monte Carlo pedigree disequilibrium test (MCPDT) to determine interesting regions for the Adult Treatment Panel (ATP) binary trait. Then eLBL was applied to haplotype blocks covering the flagged SNPs in Step 1. Several significantly associated haplotypes were identified; most are in blocks contained in protein coding genes that appear to be relevant for metabolic syndrome. The results are further substantiated with a Type I error study and by an additional analysis using the triglyceride measurements directly as a quantitative trait.
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