arXiv subjects

Tianjian Zhou

Publications and source records attributed to Tianjian Zhou.

15 recordsLinked to original sources

arXiv2026

Mixture of Finite Mixtures Model for Basket Trial

With the recent paradigm shift from cytotoxic drugs to new generation of target therapy and immuno-oncology therapy during oncology drug developments, patients with various cancer (sub)types may be eligible to participate in a basket trial if they have the same molecular target. Bayesian hierarchical modeling (BHM) are widely used in basket trial data analysis, where they adaptively borrow information among different cohorts (subtypes) rather than fully pool the data together or doing stratified analysis based on each cohort. Those approaches, however, may have the risk of over shrinkage estimation because of the invalidated exchangeable assumption. We propose a two-step procedure to find the balance between pooled and stratified analysis. In the first step, we treat it as a clustering problem by grouping cohorts into clusters that share the similar treatment effect. In the second step, we use shrinkage estimator from BHM to estimate treatment effects for cohorts within each cluster under exchangeable assumption. For clustering part, we adapt the mixture of finite mixtures (MFM) approach to have consistent estimate of the number of clusters. We investigate the performance of our proposed method in simulation studies and apply this method to Vemurafenib basket trial data analysis.

stat.ME↗

arXiv2026

P-SLCR: Unsupervised Point Cloud Semantic Segmentation via Prototypes Structure Learning and Consistent Reasoning

Current semantic segmentation approaches for point cloud scenes heavily rely on manual labeling, while research on unsupervised semantic segmentation methods specifically for raw point clouds is still in its early stages. Unsupervised point cloud learning poses significant challenges due to the absence of annotation information and the lack of pre-training. The development of effective strategies is crucial in this context. In this paper, we propose a novel prototype library-driven unsupervised point cloud semantic segmentation strategy that utilizes Structure Learning and Consistent Reasoning (P-SLCR). First, we propose a Consistent Structure Learning to establish structural feature learning between consistent points and the library of consistent prototypes by selecting high-quality features. Second, we propose a Semantic Relation Consistent Reasoning that constructs a prototype inter-relation matrix between consistent and ambiguous prototype libraries separately. This process ensures the preservation of semantic consistency by imposing constraints on consistent and ambiguous prototype libraries through the prototype inter-relation matrix. Finally, our method was extensively evaluated on the S3DIS, SemanticKITTI, and Scannet datasets, achieving the best performance compared to unsupervised methods. Specifically, the mIoU of 47.1% is achieved for Area-5 of the S3DIS dataset, surpassing the classical fully supervised method PointNet by 2.5%.

cs.CV↗

arXiv2023

PAM-HC: A Bayesian Nonparametric Construction of Hybrid Control for Randomized Clinical Trials Using External Data

It is highly desirable to borrow information from external data to augment a control arm in a randomized clinical trial, especially in settings where the sample size for the control arm is limited. However, a main challenge in borrowing information from external data is to accommodate potential heterogeneous subpopulations across the external and trial data. We apply a Bayesian nonparametric model called Plaid Atoms Model (PAM) to identify overlapping and unique subpopulations across datasets, with which we restrict the information borrowing to the common subpopulations. This forms a hybrid control (HC) that leads to more precise estimation of treatment effects Simulation studies demonstrate the robustness of the new method, and an application to an Atopic Dermatitis dataset shows improved treatment effect estimation.

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arXiv2023

Statistical Frameworks for Oncology Dose-Finding Designs with Late-Onset Toxicities: A Review

In oncology dose-finding trials, due to staggered enrollment, it might be desirable to make dose-assignment decisions in real-time in the presence of pending toxicity outcomes, for example, when the dose-limiting toxicity is late-onset. Patients' time-to-event information may be utilized to facilitate such decisions. We review statistical frameworks for time-to-event modeling in dose-finding trials and summarize existing designs into two classes: TITE designs and POD designs. TITE designs are based on inference on toxicity probabilities, while POD designs are based on inference on dose-finding decisions. These two classes of designs contain existing individual designs as special cases and also give rise to new designs. We discuss and study the theoretical properties of these designs, including large-sample convergence properties, coherence principles, and the underlying decision rules. To facilitate the use of these designs in practice, we introduce efficient computational algorithms and review common practical considerations, such as safety rules and suspension rules. Finally, the operating characteristics of several designs are evaluated and compared through computer simulations.

stat.ME↗

arXiv2023

On Bayesian Sequential Clinical Trial Designs

Clinical trials usually involve sequential patient entry. When designing a clinical trial, it is often desirable to include a provision for interim analyses of accumulating data with the potential for stopping the trial early. We review Bayesian sequential clinical trial designs based on posterior probabilities, posterior predictive probabilities, and decision-theoretic frameworks. A pertinent question is whether Bayesian sequential designs need to be adjusted for the planning of interim analyses. We answer this question from three perspectives: a frequentist-oriented perspective, a calibrated Bayesian perspective, and a subjective Bayesian perspective. We also provide new insights into the likelihood principle, which is commonly tied to statistical inference and decision making in sequential clinical trials. Some theoretical results are derived, and numerical studies are conducted to illustrate and assess these designs.

stat.ME↗

arXiv2021

The Ci3+3 Design for Dual-Agent Combination Dose-Finding Clinical Trials

We propose a rule-based statistical design for combination dose-finding trials with two agents. The Ci3+3 design is an extension of the i3+3 design with simple decision rules comparing the observed toxicity rates and equivalence intervals that define the maximum tolerated dose combination. Ci3+3 consists of two stages to allow fast and efficient exploration of the dose-combination space. Statistical inference is restricted to a beta-binomial model for dose evaluation, and the entire design is built upon a set of fixed rules. We show via simulation studies that the Ci3+3 design exhibits similar and comparable operating characteristics to more complex designs utilizing model-based inferences. We believe that the Ci3+3 design may provide an alternative choice to help simplify the design and conduct of combination dose-finding trials in practice.

stat.AP↗

arXiv2021

Tracking the Transmission Dynamics of COVID-19 with a Time-Varying Coefficient State-Space Model

The spread of COVID-19 has been greatly impacted by regulatory policies and behavior patterns that vary across counties, states, and countries. Population-level dynamics of COVID-19 can generally be described using a set of ordinary differential equations, but these deterministic equations are insufficient for modeling the observed case rates, which can vary due to local testing and case reporting policies and non-homogeneous behavior among individuals. To assess the impact of population mobility on the spread of COVID-19, we have developed a novel Bayesian time-varying coefficient state-space model for infectious disease transmission. The foundation of this model is a time-varying coefficient compartment model to recapitulate the dynamics among susceptible, exposed, undetected infectious, detected infectious, undetected removed, detected non-infectious, detected recovered, and detected deceased individuals. The infectiousness and detection parameters are modeled to vary by time, and the infectiousness component in the model incorporates information on multiple sources of population mobility. Along with this compartment model, a multiplicative process model is introduced to allow for deviation from the deterministic dynamics. We apply this model to observed COVID-19 cases and deaths in several US states and Colorado counties. We find that population mobility measures are highly correlated with transmission rates and can explain complicated temporal variation in infectiousness in these regions. Additionally, the inferred connections between mobility and epidemiological parameters, varying across locations, have revealed the heterogeneous effects of different policies on the dynamics of COVID-19.

stat.AP↗

arXiv2021

Incorporating External Data into the Analysis of Clinical Trials via Bayesian Additive Regression Trees

Most clinical trials involve the comparison of a new treatment to a control arm (e.g., the standard of care) and the estimation of a treatment effect. External data, including historical clinical trial data and real-world observational data, are commonly available for the control arm. Borrowing information from external data holds the promise of improving the estimation of relevant parameters and increasing the power of detecting a treatment effect if it exists. In this paper, we propose to use Bayesian additive regression trees (BART) for incorporating external data into the analysis of clinical trials, with a specific goal of estimating the conditional or population average treatment effect. BART naturally adjusts for patient-level covariates and captures potentially heterogeneous treatment effects across different data sources, achieving flexible borrowing. Simulation studies demonstrate that BART compares favorably to a hierarchical linear model and a normal-normal hierarchical model. We illustrate the proposed method with an acupuncture trial.

stat.ME↗

arXiv2020

Semiparametric Bayesian Inference for the Transmission Dynamics of COVID-19 with a State-Space Model

The outbreak of Coronavirus Disease 2019 (COVID-19) is an ongoing pandemic affecting over 200 countries and regions. Inference about the transmission dynamics of COVID-19 can provide important insights into the speed of disease spread and the effects of mitigation policies. We develop a novel Bayesian approach to such inference based on a probabilistic compartmental model using data of daily confirmed COVID-19 cases. In particular, we consider a probabilistic extension of the classical susceptible-infectious-recovered model, which takes into account undocumented infections and allows the epidemiological parameters to vary over time. We estimate the disease transmission rate via a Gaussian process prior, which captures nonlinear changes over time without the need of specific parametric assumptions. We utilize a parallel-tempering Markov chain Monte Carlo algorithm to efficiently sample from the highly correlated posterior space. Predictions for future observations are done by sampling from their posterior predictive distributions. Performance of the proposed approach is assessed using simulated datasets. Finally, our approach is applied to COVID-19 data from four states of the United States: Washington, New York, California, and Illinois. An R package BaySIR is made available at https://github.com/tianjianzhou/BaySIR for the public to conduct independent analysis or reproduce the results in this paper.

stat.ME↗

arXiv2020

MUCE: Bayesian Hierarchical Modeling for the Design and Analysis of Phase 1b Multiple Expansion Cohort Trials

We propose a multiple cohort expansion (MUCE) approach as a design or analysis method for phase 1b multiple expansion cohort trials, which are novel first-in-human studies conducted following phase 1a dose escalation. The MUCE design is based on a class of Bayesian hierarchical models that adaptively borrow information across arms. Statistical inference is directly based on the posterior probability of each arm being efficacious, facilitating the decision making that decides which arm to select for further testing.

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arXiv2019

PoD-TPI: Probability-of-Decision Toxicity Probability Interval Design to Accelerate Phase I Trials

Cohort-based enrollment can slow down dose-finding trials since the outcomes of the previous cohort must be fully evaluated before the next cohort can be enrolled. This results in frequent suspension of patient enrollment. The issue is exacerbated in recent immune-oncology trials where toxicity outcomes can take a long time to observe. We propose a novel phase I design, the probability-of-decision toxicity probability interval (PoD-TPI) design, to accelerate phase I trials. PoD-TPI enables dose assignment in real-time in the presence of pending toxicity outcomes. With uncertain outcomes, the dose assignment decisions are treated as a random variable, and we calculate the posterior distribution of the decisions. The posterior distribution reflects the variability in the pending outcomes and allows a direct and intuitive evaluation of the confidence of all possible decisions. Optimal decisions are calculated based on 0-1 loss, and extra safety rules are constructed to enforce sufficient protection from exposing patients to risky doses. A new and useful feature of PoD-TPI is that it allows investigators and regulators to balance the trade-off between enrollment speed and making risky decisions by tuning a pair of intuitive design parameters. Through numerical studies, we evaluate the operating characteristics of PoD-TPI and demonstrate that PoD-TPI shortens trial duration and maintains trial safety and efficiency compared to existing time-to-event designs.

stat.AP↗

arXiv2019

Posterior Contraction Rate of Sparse Latent Feature Models with Application to Proteomics

The Indian buffet process (IBP) and phylogenetic Indian buffet process (pIBP) can be used as prior models to infer latent features in a data set. The theoretical properties of these models are under-explored, however, especially in high dimensional settings. In this paper, we show that under mild sparsity condition, the posterior distribution of the latent feature matrix, generated via IBP or pIBP priors, converges to the true latent feature matrix asymptotically. We derive the posterior convergence rate, referred to as the contraction rate. We show that the convergence holds even when the dimensionality of the latent feature matrix increases with the sample size, therefore making the posterior inference valid in high dimensional setting. We demonstrate the theoretical results using computer simulation, in which the parallel-tempering Markov chain Monte Carlo method is applied to overcome computational hurdles. The practical utility of the derived properties is demonstrated by inferring the latent features in a reverse phase protein arrays (RPPA) dataset under the IBP prior model. Software and dataset reported in the manuscript are provided at http://www.compgenome.org/IBP.

stat.AP↗

arXiv2017

Bayesian Nonparametric Models for Biomedical Data Analysis

In this dissertation, we develop nonparametric Bayesian models for biomedical data analysis. In particular, we focus on inference for tumor heterogeneity and inference for missing data. First, we present a Bayesian feature allocation model for tumor subclone reconstruction using mutation pairs. The key innovation lies in the use of short reads mapped to pairs of proximal single nucleotide variants (SNVs). In contrast, most existing methods use only marginal reads for unpaired SNVs. In the same context of using mutation pairs, in order to recover the phylogenetic relationship of subclones, we then develop a Bayesian treed feature allocation model. In contrast to commonly used feature allocation models, we allow the latent features to be dependent, using a tree structure to introduce dependence. Finally, we propose a nonparametric Bayesian approach to monotone missing data in longitudinal studies with non-ignorable missingness. In contrast to most existing methods, our method allows for incorporating information from auxiliary covariates and is able to capture complex structures among the response, missingness and auxiliary covariates. Our models are validated through simulation studies and are applied to real-world biomedical datasets.

stat.AP↗

arXiv2017

TreeClone: Reconstruction of Tumor Subclone Phylogeny Based on Mutation Pairs using Next Generation Sequencing Data

We present TreeClone, a latent feature allocation model to reconstruct tumor subclones subject to phylogenetic evolution that mimics tumor evolution. Similar to most current methods, we consider data from next-generation sequencing of tumor DNA. Unlike most methods that use information in short reads mapped to single nucleotide variants (SNVs), we consider subclone phylogeny reconstruction using pairs of two proximal SNVs that can be mapped by the same short reads. As part of the Bayesian inference model, we construct a phylogenetic tree prior. The use of the tree structure in the prior greatly strengthens inference. Only subclones that can be explained by a phylogenetic tree are assigned non-negligible probabilities. The proposed Bayesian framework implies posterior distributions on the number of subclones, their genotypes, cellular proportions, and the phylogenetic tree spanned by the inferred subclones. The proposed method is validated against different sets of simulated and real-world data using single and multiple tumor samples. An open source software package is available at http://www.compgenome.org/treeclone.

stat.AP↗

arXiv2017

PairClone: A Bayesian Subclone Caller Based on Mutation Pairs

Tumor cell populations can be thought of as being composed of homogeneous cell subpopulations, with each subpopulation being characterized by overlapping sets of single nucleotide variants (SNVs). Such subpopulations are known as subclones and are an important target for precision medicine. Reconstructing such subclones from next-generation sequencing (NGS) data is one of the major challenges in precision medicine. We present PairClone as a new tool to implement this reconstruction. The main idea of PairClone is to model short reads mapped to pairs of proximal SNVs. In contrast, most existing methods use only marginal reads for unpaired SNVs. Using Bayesian nonparametric models, we estimate posterior probabilities of the number, genotypes and population frequencies of subclones in one or more tumor sample. We use the categorical Indian buffet process (cIBP) as a prior probability model for subclones that are represented as vectors of categorical matrices that record the corresponding sets of mutation pairs. Performance of PairClone is assessed using simulated and real datasets. An open source software package can be obtained at http://www.compgenome.org/pairclone.

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