Biometrics最新文献

Convolutional neural networks (CNNs) provide flexible function approximations for a wide variety of applications when the input variables are in the form of images or spatial data. Although CNNs often outperform traditional statistical models in prediction accuracy, statistical inference, such as estimating the effects of covariates and quantifying the prediction uncertainty, is not trivial due to the highly complicated model structure and overparameterization. To address this challenge, we propose a new Bayesian approach by embedding CNNs within the generalized linear models (GLMs) framework. We use extracted nodes from the last hidden layer of CNN with Monte Carlo (MC) dropout as informative covariates in GLM. This improves accuracy in prediction and regression coefficient inference, allowing for the interpretation of coefficients and uncertainty quantification. By fitting ensemble GLMs across multiple realizations from MC dropout, we can account for uncertainties in extracting the features. We apply our methods to biological and epidemiological problems, which have both high-dimensional correlated inputs and vector covariates. Specifically, we consider malaria incidence data, brain tumor image data, and fMRI data. By extracting information from correlated inputs, the proposed method can provide an interpretable Bayesian analysis. The algorithm can be broadly applicable to image regressions or correlated data analysis by enabling accurate Bayesian inference quickly.

To leverage the advancements in genome-wide association studies (GWAS) and quantitative trait loci (QTL) mapping for traits and molecular phenotypes to gain mechanistic understanding of the genetic regulation, biological researchers often investigate the expression QTLs (eQTLs) that colocalize with QTL or GWAS peaks. Our research is inspired by 2 such studies. One aims to identify the causal single nucleotide polymorphisms that are responsible for the phenotypic variation and whose effects can be explained by their impacts at the transcriptomic level in maize. The other study in mouse focuses on uncovering the cis-driver genes that induce phenotypic changes by regulating trans-regulated genes. Both studies can be formulated as mediation problems with potentially high-dimensional exposures, confounders, and mediators that seek to estimate the overall indirect effect (IE) for each exposure. In this paper, we propose MedDiC, a novel procedure to estimate the overall IE based on difference-in-coefficients approach. Our simulation studies find that MedDiC offers valid inference for the IE with higher power, shorter confidence intervals, and faster computing time than competing methods. We apply MedDiC to the 2 aforementioned motivating datasets and find that MedDiC yields reproducible outputs across the analysis of closely related traits, with results supported by external biological evidence. The code and additional information are available on our GitHub page (https://github.com/QiZhangStat/MedDiC).

We develop a method for hybrid analyses that uses external controls to augment internal control arms in randomized controlled trials (RCTs) where the degree of borrowing is determined based on similarity between RCT and external control patients to account for systematic differences (e.g., unmeasured confounders). The method represents a novel extension of the power prior where discounting weights are computed separately for each external control based on compatibility with the randomized control data. The discounting weights are determined using the predictive distribution for the external controls derived via the posterior distribution for time-to-event parameters estimated from the RCT. This method is applied using a proportional hazards regression model with piecewise constant baseline hazard. A simulation study and a real-data example are presented based on a completed trial in non-small cell lung cancer. It is shown that the case weighted power prior provides robust inference under various forms of incompatibility between the external controls and RCT population.

Deep learning has continuously attained huge success in diverse fields, while its application to survival data analysis remains limited and deserves further exploration. For the analysis of current status data, a deep partially linear Cox model is proposed to circumvent the curse of dimensionality. Modeling flexibility is attained by using deep neural networks (DNNs) to accommodate nonlinear covariate effects and monotone splines to approximate the baseline cumulative hazard function. We establish the convergence rate of the proposed maximum likelihood estimators. Moreover, we derive that the finite-dimensional estimator for treatment covariate effects is $sqrt{n}$-consistent, asymptotically normal, and attains semiparametric efficiency. Finally, we demonstrate the performance of our procedures through extensive simulation studies and application to real-world data on news popularity.

Fish growth models are crucial for fisheries stock assessments and are commonly estimated using fish length-at-age data. This data is widely collected using length-stratified age sampling (LSAS), a cost-effective two-phase response-selective sampling method. The data may contain age measurement errors (MEs). We propose a methodology that accounts for both LSAS and age MEs to accurately estimate fish growth. The proposed methods use empirical proportion likelihood methodology for LSAS and the structural errors in variables methodology for age MEs. We provide a measure of uncertainty for parameter estimates and standardized residuals for model validation. To model the age distribution, we employ a continuation ratio-logit model that is consistent with the random nature of the true age distribution. We also apply a discretization approach for age and length distributions, which significantly improves computational efficiency and is consistent with the discrete age and length data typically encountered in practice. Our simulation study shows that neglecting age MEs can lead to significant bias in growth estimation, even with small but non-negligible age MEs. However, our new approach performs well regardless of the magnitude of age MEs and accurately estimates SEs of parameter estimators. Real data analysis demonstrates the effectiveness of the proposed model validation device. Computer codes to implement the methodology are provided.

The marginal structure quantile model (MSQM) provides a unique lens to understand the causal effect of a time-varying treatment on the full distribution of potential outcomes. Under the semiparametric framework, we derive the efficiency influence function for the MSQM, from which a new doubly robust estimator is proposed for point estimation and inference. We show that the doubly robust estimator is consistent if either of the models associated with treatment assignment or the potential outcome distributions is correctly specified, and is semiparametric efficient if both models are correct. To implement the doubly robust MSQM estimator, we propose to solve a smoothed estimating equation to facilitate efficient computation of the point and variance estimates. In addition, we develop a confounding function approach to investigate the sensitivity of several MSQM estimators when the sequential ignorability assumption is violated. Extensive simulations are conducted to examine the finite-sample performance characteristics of the proposed methods. We apply the proposed methods to the Yale New Haven Health System Electronic Health Record data to study the effect of antihypertensive medications to patients with severe hypertension and assess the robustness of the findings to unmeasured baseline and time-varying confounding.

Brain-effective connectivity analysis quantifies directed influence of one neural element or region over another, and it is of great scientific interest to understand how effective connectivity pattern is affected by variations of subject conditions. Vector autoregression (VAR) is a useful tool for this type of problems. However, there is a paucity of solutions when there is measurement error, when there are multiple subjects, and when the focus is the inference of the transition matrix. In this article, we study the problem of transition matrix inference under the high-dimensional VAR model with measurement error and multiple subjects. We propose a simultaneous testing procedure, with three key components: a modified expectation-maximization (EM) algorithm, a test statistic based on the tensor regression of a bias-corrected estimator of the lagged auto-covariance given the covariates, and a properly thresholded simultaneous test. We establish the uniform consistency for the estimators of our modified EM, and show that the subsequent test achieves both a consistent false discovery control, and its power approaches one asymptotically. We demonstrate the efficacy of our method through both simulations and a brain connectivity study of task-evoked functional magnetic resonance imaging.

When studying the treatment effect on time-to-event outcomes, it is common that some individuals never experience failure events, which suggests that they have been cured. However, the cure status may not be observed due to censoring which makes it challenging to define treatment effects. Current methods mainly focus on estimating model parameters in various cure models, ultimately leading to a lack of causal interpretations. To address this issue, we propose 2 causal estimands, the timewise risk difference and mean survival time difference, in the always-uncured based on principal stratification as a complement to the treatment effect on cure rates. These estimands allow us to study the treatment effects on failure times in the always-uncured subpopulation. We show the identifiability using a substitutional variable for the potential cure status under ignorable treatment assignment mechanism, these 2 estimands are identifiable. We also provide estimation methods using mixture cure models. We applied our approach to an observational study that compared the leukemia-free survival rates of different transplantation types to cure acute lymphoblastic leukemia. Our proposed approach yielded insightful results that can be used to inform future treatment decisions.

Limitations of using the traditional Cox's hazard ratio for summarizing the magnitude of the treatment effect on time-to-event outcomes have been widely discussed, and alternative measures that do not have such limitations are gaining attention. One of the alternative methods recently proposed, in a simple 2-sample comparison setting, uses the average hazard with survival weight (AH), which can be interpreted as the general censoring-free person-time incidence rate on a given time window. In this paper, we propose a new regression analysis approach for the AH with a truncation time τ. We investigate 3 versions of AH regression analysis, assuming (1) independent censoring, (2) group-specific censoring, and (3) covariate-dependent censoring. The proposed AH regression methods are closely related to robust Poisson regression. While the new approach needs to require a truncation time τ explicitly, it can be more robust than Poisson regression in the presence of censoring. With the AH regression approach, one can summarize the between-group treatment difference in both absolute difference and relative terms, adjusting for covariates that are associated with the outcome. This property will increase the likelihood that the treatment effect magnitude is correctly interpreted. The AH regression approach can be a useful alternative to the traditional Cox's hazard ratio approach for estimating and reporting the magnitude of the treatment effect on time-to-event outcomes.