arXiv subjects

Cliburn Chan

Publications and source records attributed to Cliburn Chan.

6 recordsLinked to original sources

arXiv2023

Cocaine Use Prediction with Tensor-based Machine Learning on Multimodal MRI Connectome Data

This paper considers the use of machine learning algorithms for predicting cocaine use based on magnetic resonance imaging (MRI) connectomic data. The study utilized functional MRI (fMRI) and diffusion MRI (dMRI) data collected from 275 individuals, which was then parcellated into 246 regions of interest (ROIs) using the Brainnetome atlas. After data preprocessing, the datasets were transformed into tensor form. We developed a tensor-based unsupervised machine learning algorithm to reduce the size of the data tensor from $275$ (individuals) $\times 2$ (fMRI and dMRI) $\times 246$ (ROIs) $\times 246$ (ROIs) to $275$ (individuals) $\times 2$ (fMRI and dMRI) $\times 6$ (clusters) $\times 6$ (clusters). This was achieved by applying the high-order Lloyd algorithm to group the ROI data into 6 clusters. Features were extracted from the reduced tensor and combined with demographic features (age, gender, race, and HIV status). The resulting dataset was used to train a Catboost model using subsampling and nested cross-validation techniques, which achieved a prediction accuracy of 0.857 for identifying cocaine users. The model was also compared with other models, and the feature importance of the model was presented. Overall, this study highlights the potential for using tensor-based machine learning algorithms to predict cocaine use based on MRI connectomic data and presents a promising approach for identifying individuals at risk of substance abuse.

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arXiv2022

A tree perspective on stick-breaking models in covariate-dependent mixtures

Stick-breaking (SB) processes are often adopted in Bayesian mixture models for generating mixing weights. When covariates influence the sizes of clusters, SB mixtures are particularly convenient as they can leverage their connection to binary regression to ease both the specification of covariate effects and posterior computation. Existing SB models are typically constructed based on continually breaking a single remaining piece of the unit stick. We view this from a dyadic tree perspective in terms of a lopsided bifurcating tree that extends only in one side. We show that two unsavory characteristics of SB models are in fact largely due to this lopsided tree structure. We consider a generalized class of SB models with alternative bifurcating tree structures and examine the influence of the underlying tree topology on the resulting Bayesian analysis in terms of prior assumptions, posterior uncertainty, and computational effectiveness. In particular, we provide evidence that a balanced tree topology, which corresponds to continually breaking all remaining pieces of the unit stick, can resolve or mitigate these undesirable properties of SB models that rely on a lopsided tree.

stat.ME↗

arXiv2021

TEAM: A Multiple Testing Algorithm on the Aggregation Tree for Flow Cytometry Analysis

In immunology studies, flow cytometry is a commonly used multivariate single-cell assay. One key goal in flow cytometry analysis is to pinpoint the immune cells responsive to certain stimuli. Statistically, this problem can be translated into comparing two protein expression probability density functions (PDFs) before and after the stimulus; the goal is to pinpoint the regions where these two pdfs differ. In this paper, we model this comparison as a multiple testing problem. First, we partition the sample space into small bins. In each bin we form a hypothesis to test the existence of differential pdfs. Second, we develop a novel multiple testing method, called TEAM (Testing on the Aggregation tree Method), to identify those bins that harbor differential pdfs while controlling the false discovery rate (FDR) under the desired level. TEAM embeds the testing procedure into an aggregation tree to test from fine- to coarse-resolution. The procedure achieves the statistical goal of pinpointing differential pdfs to the smallest possible regions. TEAM is computationally efficient, capable of analyzing large flow cytometry data sets in much shorter time compared with competing methods. We applied TEAM and competing methods on a flow cytometry data set to identify T cells responsive to the cytomeglovirus (CMV)-pp65 antigen stimulation. TEAM successfully identified the monofunctional, bifunctional, and polyfunctional T cells while the competing methods either did not finish in a reasonable time frame or provided less interpretable results. Numerical simulations and theoretical justifications demonstrate that TEAM has asymptotically valid, powerful, and robust performance. Overall, TEAM is a computationally efficient and statistically powerful algorithm that can yield meaningful biological insights in flow cytometry studies.

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arXiv2020

Coarsened mixtures of hierarchical skew normal kernels for flow cytometry analyses

Flow cytometry (FCM) is the standard multi-parameter assay for measuring single cell phenotype and functionality. It is commonly used for quantifying the relative frequencies of cell subsets in blood and disaggregated tissues. A typical analysis of FCM data involves cell classification---that is, the identification of cell subgroups in the sample---and comparisons of the cell subgroups across samples or conditions. While modern experiments often necessitate the collection and processing of samples in multiple batches, analysis of FCM data across batches is challenging because differences across samples may occur due to either true biological variation or technical reasons such as antibody lot effects or instrument optics across batches. Thus a critical step in comparative analyses of multi-sample FCM data---yet missing in existing automated methods for analyzing such data---is cross-sample calibration, whose goal is to align corresponding cell subsets across multiple samples in the presence of technical variations, so that biological variations can be meaningfully compared. We introduce a Bayesian nonparametric hierarchical modeling approach for accomplishing both calibration and cell classification simultaneously in a unified probabilistic manner. Three important features of our method make it particularly effective for analyzing multi-sample FCM data: a nonparametric mixture avoids prespecifying the number of cell clusters; a hierarchical skew normal kernel that allows flexibility in the shapes of the cell subsets and cross-sample variation in their locations; and finally the "coarsening" strategy makes inference robust to departures from the model such as heavy-tailness not captured by the skew normal kernels. We demonstrate the merits of our approach in simulated examples and carry out a case study in the analysis of two multi-sample FCM data sets.

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arXiv2017

Bayesian Multi Plate High Throughput Screening of Compounds

High throughput screening of compounds (chemicals) is an essential part of drug discovery [7], involving thousands to millions of compounds, with the purpose of identifying candidate hits. Most statistical tools, including the industry standard B-score method, work on individual compound plates and do not exploit cross-plate correlation or statistical strength among plates. We present a new statistical framework for high throughput screening of compounds based on Bayesian nonparametric modeling. The proposed approach is able to identify candidate hits from multiple plates simultaneously, sharing statistical strength among plates and providing more robust estimates of compound activity. It can flexibly accommodate arbitrary distributions of compound activities and is applicable to any plate geometry. The algorithm provides a principled statistical approach for hit identification and false discovery rate control. Experiments demonstrate significant improvements in hit identification sensitivity and specificity over the B-score method, which is highly sensitive to threshold choice. The framework is implemented as an efficient R extension package BHTSpack and is suitable for large scale data sets.

stat.ML↗

arXiv2016

Bayesian analysis of immune response dynamics with sparse time series data

In vaccine development, the temporal profiles of relative abundance of subtypes of immune cells (T-cells) is key to understanding vaccine efficacy. Complex and expensive experimental studies generate very sparse time series data on this immune response. Fitting multi-parameter dynamic models of the immune response dynamics-- central to evaluating mechanisms underlying vaccine efficacy-- is challenged by data sparsity. The research reported here addresses this challenge. For HIV/SIV vaccine studies in macaques, we: (a) introduce novel dynamic models of progression of cellular populations over time with relevant, time-delayed components reflecting the vaccine response; (b) define an effective Bayesian model fitting strategy that couples Markov chain Monte Carlo (MCMC) with Approximate Bayesian Computation (ABC)-- building on the complementary strengths of the two approaches, neither of which is effective alone; (c) explore questions of information content in the sparse time series for each of the model parameters, linking into experimental design and model simplification for future experiments; and (d) develop, apply and compare the analysis with samples from a recent HIV/SIV experiment, with novel insights and conclusions about the progressive response to the vaccine, and how this varies across subjects.

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