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Bayesian Nonparametrics and Biostatistics: The Case of PET Imaging 贝叶斯非参数和生物统计学:以PET成像为例
IF 1.2 4区 数学 Pub Date : 2019-11-01 DOI: 10.1515/ijb-2017-0099
Mame Diarra Fall
Abstract Biostatistic applications often require to collect and analyze a massive amount of data. Hence, it has become necessary to consider new statistical paradigms that perform well in characterizing complex data. Nonparametric Bayesian methods provide a widely used framework that offers the key advantages of a fully model-based probabilistic framework, while being highly flexible and adaptable. The goal of this paper is to provide a motivation of Bayesian nonparametrics (BNP) through a particular biomedical application, namely Positron Emission Tomography (PET) imaging reconstruction.
摘要生物统计学应用程序通常需要收集和分析大量数据。因此,有必要考虑在表征复杂数据方面表现良好的新统计范式。非参数贝叶斯方法提供了一个广泛使用的框架,它提供了完全基于模型的概率框架的关键优势,同时具有高度的灵活性和适应性。本文的目标是通过一个特定的生物医学应用,即正电子发射断层扫描(PET)成像重建,提供贝叶斯非框架(BNP)的动机。
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引用次数: 0
On the Use of Optimal Transportation Theory to Recode Variables and Application to Database Merging 最优运输理论在变量重编码中的应用及其在数据库合并中的应用
IF 1.2 4区 数学 Pub Date : 2019-09-14 DOI: 10.1515/ijb-2018-0106
Valérie Garès, C. Dimeglio, G. Guernec, Romain Fantin, B. Lepage, M. Kosorok, N. Savy
Abstract Merging databases is a strategy of paramount interest especially in medical research. A common problem in this context comes from a variable which is not coded on the same scale in both databases we aim to merge. This paper considers the problem of finding a relevant way to recode the variable in order to merge these two databases. To address this issue, an algorithm, based on optimal transportation theory, is proposed. Optimal transportation theory gives us an application to map the measure associated with the variable in database A to the measure associated with the same variable in database B. To do so, a cost function has to be introduced and an allocation rule has to be defined. Such a function and such a rule is proposed involving the information contained in the covariates. In this paper, the method is compared to multiple imputation by chained equations and a statistical learning method and has demonstrated a better average accuracy in many situations. Applications on both simulated and real datasets show that the efficiency of the proposed merging algorithm depends on how the covariates are linked with the variable of interest.
摘要数据库合并是一种非常重要的策略,特别是在医学研究中。在这种情况下,一个常见的问题来自于一个变量,该变量在我们打算合并的两个数据库中没有以相同的规模编码。本文考虑的问题是找到一种相关的方法来重新编码变量,以便合并这两个数据库。为了解决这一问题,提出了一种基于最优运输理论的算法。最优运输理论为我们提供了一个应用程序,将与数据库A中变量相关的度量映射到与数据库b中相同变量相关的度量。要做到这一点,必须引入成本函数并定义分配规则。提出了一个包含协变量信息的函数和规则。本文将该方法与链式多次插值法和统计学习法进行了比较,结果表明该方法在许多情况下具有更好的平均精度。在模拟和实际数据集上的应用表明,所提出的合并算法的效率取决于协变量与感兴趣变量的联系方式。
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引用次数: 5
Multinomial Logistic Model for Coinfection Diagnosis Between Arbovirus and Malaria in Kedougou 可斗沟虫媒病毒与疟疾共感染诊断的多项Logistic模型
IF 1.2 4区 数学 Pub Date : 2018-01-12 DOI: 10.1515/ijb-2017-0015
Mor Absa Loum, Marie-Anne Poursat, A. Sow, A. Sall, C. Loucoubar, E. Gassiat
Abstract In tropical regions, populations continue to suffer morbidity and mortality from malaria and arboviral diseases. In Kedougou (Senegal), these illnesses are all endemic due to the climate and its geographical position. The co-circulation of malaria parasites and arboviruses can explain the observation of coinfected cases. Indeed there is strong resemblance in symptoms between these diseases making problematic targeted medical care of coinfected cases. This is due to the fact that the origin of illness is not obviously known. Some cases could be immunized against one or the other of the pathogens, immunity typically acquired with factors like age and exposure as usual for endemic area. Thus, coinfection needs to be better diagnosed. Using data collected from patients in Kedougou region, from 2009 to 2013, we adjusted a multinomial logistic model and selected relevant variables in explaining coinfection status. We observed specific sets of variables explaining each of the diseases exclusively and the coinfection. We tested the independence between arboviral and malaria infections and derived coinfection probabilities from the model fitting. In case of a coinfection probability greater than a threshold value to be calibrated on the data, long duration of illness and age are mostly indicative of arboviral disease while high body temperature and presence of nausea or vomiting symptoms during the rainy season are mostly indicative of malaria disease.
在热带地区,人们继续遭受疟疾和虫媒病毒疾病的发病率和死亡率。在凯杜古(塞内加尔),由于气候和地理位置的原因,这些疾病都是地方性的。疟疾寄生虫和虫媒病毒的共同传播可以解释合并感染病例的观察结果。事实上,这些疾病之间的症状非常相似,这使得对合并感染病例的针对性医疗护理存在问题。这是因为疾病的起源还不清楚。有些病例可以针对一种或另一种病原体进行免疫接种,免疫通常与流行地区的年龄和暴露等因素有关。因此,需要更好地诊断合并感染。利用2009 - 2013年可斗沟地区患者的数据,调整多项logistic模型并选择相关变量来解释合并感染状况。我们观察到一组特定的变量来单独解释每种疾病和合并感染。我们测试了虫媒病毒和疟疾感染之间的独立性,并从模型拟合中得出了共同感染的概率。如果合并感染的概率大于根据数据校准的阈值,病程长和年龄大则大多表明患有虫媒病毒病,而在雨季出现高体温和恶心或呕吐症状则大多表明患有疟疾。
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引用次数: 2
Cell Line Classification Using Electric Cell-Substrate Impedance Sensing (ECIS) 基于Cell- substrate Impedance Sensing (ECIS)的细胞系分类
IF 1.2 4区 数学 Pub Date : 2017-10-26 DOI: 10.1515/ijb-2018-0083
Megan L. Gelsinger, Laura L. Tupper, D. Matteson
Abstract We present new methods for cell line classification using multivariate time series bioimpedance data obtained from electric cell-substrate impedance sensing (ECIS) technology. The ECIS technology, which monitors the attachment and spreading of mammalian cells in real time through the collection of electrical impedance data, has historically been used to study one cell line at a time. However, we show that if applied to data from multiple cell lines, ECIS can be used to classify unknown or potentially mislabeled cells, factors which have previously been associated with the reproducibility crisis in the biological literature. We assess a range of approaches to this new problem, testing different classification methods and deriving a dictionary of 29 features to characterize ECIS data. Most notably, our analysis enriches the current field by making use of simultaneous multi-frequency ECIS data, where previous studies have focused on only one frequency; using classification methods to distinguish multiple cell lines, rather than simple statistical tests that compare only two cell lines; and assessing a range of features derived from ECIS data based on their classification performance. In classification tests on fifteen mammalian cell lines, we obtain very high out-of-sample predictive accuracy. These preliminary findings provide a baseline for future large-scale studies in this field.
摘要:我们提出了使用从电细胞基质阻抗传感(ECIS)技术获得的多变量时间序列生物阻抗数据进行细胞系分类的新方法。ECIS技术通过收集电阻抗数据实时监测哺乳动物细胞的附着和扩散,历史上一直用于一次研究一个细胞系。然而,我们发现,如果应用于多个细胞系的数据,ECIS可以用于对未知或潜在错误标记的细胞进行分类,这些因素以前在生物学文献中与再现性危机有关。我们评估了一系列解决这一新问题的方法,测试了不同的分类方法,并推导了一个由29个特征组成的字典来表征ECIS数据。最值得注意的是,我们的分析通过同时使用多频率ECIS数据丰富了当前领域,而以前的研究只关注一个频率;使用分类方法来区分多个细胞系,而不是仅比较两个细胞系的简单统计测试;以及基于ECIS数据的分类性能来评估从ECIS数据导出的一系列特征。在对15种哺乳动物细胞系的分类测试中,我们获得了非常高的样本外预测准确性。这些初步发现为该领域未来的大规模研究提供了基线。
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引用次数: 17
Combinatorial Mixtures of Multiparameter Distributions: An Application to Bivariate Data 多参数分布的组合混合:在双变量数据中的应用
IF 1.2 4区 数学 Pub Date : 2017-02-16 DOI: 10.1515/ijb-2015-0064
V. Edefonti, G. Parmigiani
Abstract: We introduce combinatorial mixtures – a flexible class of models for inference on mixture distributions whose components have multidimensional parameters. The key idea is to allow each element of the component-specific parameter vectors to be shared by a subset of other components. This approach allows for mixtures that range from very flexible to very parsimonious and unifies inference on component-specific parameters with inference on the number of components. We develop Bayesian inference and computational approaches for this class of distributions, and illustrate them in an application. This work was originally motivated by the analysis of cancer subtypes: in terms of biological measures of interest, subtypes may be characterized by differences in location, scale, correlations or any of the combinations. We illustrate our approach using publicly available data on molecular subtypes of lung and prostate cancers.
摘要:我们介绍了组合混合物——一类灵活的模型,用于推断混合物分布,其成分具有多维参数。关键思想是允许特定于组件的参数向量的每个元素由其他组件的子集共享。这种方法允许从非常灵活到非常简约的混合,并将对组件特定参数的推断与对组件数量的推断统一起来。我们为这类分布开发了贝叶斯推理和计算方法,并在应用中进行了说明。这项工作最初的动机是分析癌症亚型:就感兴趣的生物学测量而言,亚型可能以位置、规模、相关性或任何组合的差异为特征。我们使用公开的肺癌和前列腺癌分子亚型的数据来说明我们的方法。
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引用次数: 0
On Stratified Adjusted Tests by Binomial Trials 二项试验的分层校正检验
IF 1.2 4区 数学 Pub Date : 2017-02-14 DOI: 10.1515/ijb-2016-0047
Asanao Shimokawa, E. Miyaoka
Abstract To estimate or test the treatment effect in randomized clinical trials, it is important to adjust for the potential influence of covariates that are likely to affect the association between the treatment or control group and the response. If these covariates are known at the start of the trial, random assignment of the treatment within each stratum would be considered. On the other hand, if these covariates are not clear at the start of the trial, or if it is difficult to allocate the treatment within each stratum, completely randomized assignment of the treatment would be performed. In both sampling structures, the use of a stratified adjusted test is a useful way to evaluate the significance of the overall treatment effect by reducing the variance and/or bias of the result. If the trial has a binary endpoint, the Cochran and Mantel-Haenszel tests are generally used. These tests are constructed based on the assumption that the number of patients within a stratum is fixed. However, in practice, the stratum sizes are not fixed at the start of the trial in many situations, and are instead allowed to vary. Therefore, there is a risk that using these tests under such situations would result in an error in the estimated variation of the test statistics. To handle the problem, we propose new test statistics under both sampling structures based on multinomial distributions. Our proposed approach is based on the Cochran test, and the difference between the two tests tends to have similar values in the case of a large number of patients. When the total number of patients is small, our approach yields a more conservative result. Through simulation studies, we show that the new approach could correctly maintain the type I error better than the traditional approach.
为了在随机临床试验中评估或检验治疗效果,重要的是要调整可能影响治疗组或对照组与反应之间关联的协变量的潜在影响。如果这些协变量在试验开始时已知,则可以考虑在每个地层中随机分配处理。另一方面,如果这些协变量在试验开始时不清楚,或者很难在每个层中分配治疗,则将执行治疗的完全随机分配。在这两种抽样结构中,使用分层调整检验是通过减少结果的方差和/或偏差来评估总体治疗效果的显著性的有用方法。如果试验有二元终点,通常使用Cochran和Mantel-Haenszel检验。这些测试是基于一个地层中患者数量是固定的假设来构建的。然而,在实践中,在许多情况下,地层尺寸在试验开始时并不是固定的,而是允许变化的。因此,在这种情况下使用这些测试可能会导致测试统计量的估计变化出现错误。为了解决这一问题,我们提出了两种抽样结构下基于多项分布的检验统计量。我们提出的方法是基于Cochran检验,在大量患者的情况下,两种检验的差值趋于相似。当患者总数较小时,我们的方法产生更保守的结果。仿真研究表明,该方法比传统方法更能正确地保持I型误差。
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引用次数: 0
Testing Equality of Treatments under an Incomplete Block Crossover Design with Ordinal Responses 具有顺序响应的不完全块体交叉设计下处理平等性的检验
IF 1.2 4区 数学 Pub Date : 2017-02-03 DOI: 10.1515/ijb-2016-0069
K. Lui
Abstract The generalized odds ratio (GOR) for paired sample is considered to measure the relative treatment effect on patient responses in ordinal data. Under a three-treatment two-period incomplete block crossover design, both asymptotic and exact procedures are developed for testing equality between treatments with ordinal responses. Monte Carlo simulation is employed to evaluate and compare the finite-sample performance of these test procedures. A discussion on advantages and disadvantages of the proposed test procedures based on the GOR versus those based on Wald’s tests under the normal random effects proportional odds model is provided. The data taken as a part of a crossover trial studying the effects of low and high doses of an analgesic versus a placebo for the relief of pain in primary dysmenorrhea over the first two periods are applied to illustrate the use of these test procedures.
摘要配对样本的广义比值比(GOR)被认为是衡量有序数据中患者反应的相对治疗效果。在三个处理两个周期的不完全块交叉设计下,开发了渐近和精确程序来测试具有顺序响应的处理之间的相等性。蒙特卡罗模拟用于评估和比较这些测试程序的有限样本性能。讨论了在正态随机效应比例优势模型下,基于GOR的测试程序与基于Wald测试的测试程序的优缺点。作为交叉试验的一部分,研究前两个时期低剂量和高剂量镇痛药与安慰剂对原发性痛经疼痛的缓解作用,应用这些数据来说明这些测试程序的使用。
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引用次数: 2
Bayesian Variable Selection Methods for Matched Case-Control Studies 匹配病例对照研究的贝叶斯变量选择方法
IF 1.2 4区 数学 Pub Date : 2017-01-31 DOI: 10.1515/ijb-2016-0043
J. Asafu-Adjei, M. Tadesse, B. Coull, R. Balasubramanian, M. Lev, L. Schwamm, R. Betensky
Abstract Matched case-control designs are currently used in many biomedical applications. To ensure high efficiency and statistical power in identifying features that best discriminate cases from controls, it is important to account for the use of matched designs. However, in the setting of high dimensional data, few variable selection methods account for matching. Bayesian approaches to variable selection have several advantages, including the fact that such approaches visit a wider range of model subsets. In this paper, we propose a variable selection method to account for case-control matching in a Bayesian context and apply it using simulation studies, a matched brain imaging study conducted at Massachusetts General Hospital, and a matched cardiovascular biomarker study conducted by the High Risk Plaque Initiative.
摘要匹配病例对照设计目前在许多生物医学应用中使用。为了确保在识别最能区分病例与对照组的特征方面具有高效率和统计能力,重要的是要考虑到匹配设计的使用。然而,在高维数据的设置中,很少有变量选择方法考虑匹配。变量选择的贝叶斯方法有几个优点,包括这样的方法访问更广泛的模型子集。在本文中,我们提出了一种变量选择方法来解释贝叶斯背景下的病例对照匹配,并使用模拟研究、马萨诸塞州总医院进行的匹配脑成像研究和高危斑块倡议进行的匹配心血管生物标志物研究将其应用。
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引用次数: 5
Joint Model for Mortality and Hospitalization 死亡率和住院率联合模型
IF 1.2 4区 数学 Pub Date : 2016-11-01 DOI: 10.1515/ijb-2016-0002
Yuqi Chen, Wensheng Guo, P. Kotanko, L. Usvyat, Yuedong Wang
Abstract: Modeling hospitalization is complicated because the follow-up time can be censored due to death. In this paper, we propose a shared frailty joint model for survival time and hospitalization. A random effect semi-parametric proportional hazard model is assumed for the survival time and conditional on the follow-up time, hospital admissions or total length of stay is modeled by a generalized linear model with a nonparametric offset function of the follow-up time. We assume that the hospitalization and the survival time are correlated through a latent subject-specific random frailty. The proposed model can be implemented using existing software such as SAS Proc NLMIXED. We demonstrate the feasibility through simulations. We apply our methods to study hospital admissions and total length of stay in a cohort of patients on hemodialysis. We identify age, albumin, neutrophil to lymphocyte ratio (NLR) and vintage as significant risk factors for mortality, and age, gender, race, albumin, NLR, pre-dialysis systolic blood pressure (preSBP), interdialytic weight gain (IDWG) and equilibrated Kt/V (eKt/V) as significant risk factors for both hospital admissions and total length of stay. In addition, hospitalization admissions is positively associated with vintage.
摘要:住院治疗的建模是复杂的,因为随访时间可能因死亡而被删减。在本文中,我们提出了一个生存时间和住院治疗的共享脆弱关节模型。假设生存时间为随机效应半参数比例风险模型,并以随访时间、住院次数或总住院时间为条件,采用具有随访时间非参数偏移函数的广义线性模型建模。我们假设住院治疗和生存时间通过潜在的受试者特异性随机脆弱性相关。所提出的模型可以使用现有的软件如SAS Proc nlmix来实现。通过仿真验证了该方法的可行性。我们应用我们的方法来研究一组血液透析患者的住院率和总住院时间。我们确定年龄、白蛋白、中性粒细胞与淋巴细胞比(NLR)和年龄是死亡率的重要危险因素,年龄、性别、种族、白蛋白、NLR、透析前收缩压(preSBP)、透析间期体重增加(IDWG)和平衡Kt/V (eKt/V)是住院和总住院时间的重要危险因素。此外,住院率与年份呈正相关。
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引用次数: 0
Effect of Smoothing in Generalized Linear Mixed Models on the Estimation of Covariance Parameters for Longitudinal Data 广义线性混合模型中平滑对纵向数据协方差参数估计的影响
IF 1.2 4区 数学 Pub Date : 2016-11-01 DOI: 10.1515/ijb-2015-0026
M. Mullah, A. Benedetti
Abstract Besides being mainly used for analyzing clustered or longitudinal data, generalized linear mixed models can also be used for smoothing via restricting changes in the fit at the knots in regression splines. The resulting models are usually called semiparametric mixed models (SPMMs). We investigate the effect of smoothing using SPMMs on the correlation and variance parameter estimates for serially correlated longitudinal normal, Poisson and binary data. Through simulations, we compare the performance of SPMMs to other simpler methods for estimating the nonlinear association such as fractional polynomials, and using a parametric nonlinear function. Simulation results suggest that, in general, the SPMMs recover the true curves very well and yield reasonable estimates of the correlation and variance parameters. However, for binary outcomes, SPMMs produce biased estimates of the variance parameters for high serially correlated data. We apply these methods to a dataset investigating the association between CD4 cell count and time since seroconversion for HIV infected men enrolled in the Multicenter AIDS Cohort Study.
广义线性混合模型除了主要用于分析聚类或纵向数据外,还可以通过限制回归样条结点处拟合的变化来实现平滑。所得到的模型通常称为半参数混合模型(spmm)。我们研究了使用spmm平滑对纵向正态、泊松和二值数据的相关和方差参数估计的影响。通过仿真,我们将spmm的性能与其他更简单的估计非线性关联的方法(如分数多项式和使用参数非线性函数)进行了比较。仿真结果表明,总体而言,spmm可以很好地恢复真实曲线,并对相关参数和方差参数给出合理的估计。然而,对于二元结果,spmm对高序列相关数据的方差参数产生偏倚估计。我们将这些方法应用于一个数据集,该数据集调查了在多中心艾滋病队列研究中登记的HIV感染男性的CD4细胞计数与血清转化时间之间的关系。
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引用次数: 4
期刊
International Journal of Biostatistics
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