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Qiwei Li

Publications and source records attributed to Qiwei Li.

34 records · Page 2Linked to original sources

A generalized Bayesian stochastic block model for microbiome community detection

Advances in next-generation sequencing technology have enabled the high-throughput profiling of metagenomes and accelerated the microbiome study. Recently, there has been a rise in quantitative studies that aim to decipher the microbiome co-occurrence network and its underlying community structure based on metagenomic sequence data. Uncovering the complex microbiome community structure is essential to understanding the role of the microbiome in disease progression and susceptibility. Taxonomic abundance data generated from metagenomic sequencing technologies are high-dimensional and compositional, suffering from uneven sampling depth, over-dispersion, and zero-inflation. These characteristics often challenge the reliability of the current methods for microbiome community detection. To this end, we propose a Bayesian stochastic block model to study the microbiome co-occurrence network based on the recently developed modified centered-log ratio transformation tailored for microbiome data analysis. Our model allows us to incorporate taxonomic tree information using a Markov random field prior. The model parameters are jointly inferred by using Markov chain Monte Carlo sampling techniques. Our simulation study showed that the proposed approach performs better than competing methods even when taxonomic tree information is non-informative. We applied our approach to a real urinary microbiome dataset from postmenopausal women, the first time the urinary microbiome co-occurrence network structure has been studied. In summary, this statistical methodology provides a new tool for facilitating advanced microbiome studies.

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Enhancing Visually-Rich Document Understanding via Layout Structure Modeling

In recent years, the use of multi-modal pre-trained Transformers has led to significant advancements in visually-rich document understanding. However, existing models have mainly focused on features such as text and vision while neglecting the importance of layout relationship between text nodes. In this paper, we propose GraphLayoutLM, a novel document understanding model that leverages the modeling of layout structure graph to inject document layout knowledge into the model. GraphLayoutLM utilizes a graph reordering algorithm to adjust the text sequence based on the graph structure. Additionally, our model uses a layout-aware multi-head self-attention layer to learn document layout knowledge. The proposed model enables the understanding of the spatial arrangement of text elements, improving document comprehension. We evaluate our model on various benchmarks, including FUNSD, XFUND and CORD, and achieve state-of-the-art results among these datasets. Our experimental results demonstrate that our proposed method provides a significant improvement over existing approaches and showcases the importance of incorporating layout information into document understanding models. We also conduct an ablation study to investigate the contribution of each component of our model. The results show that both the graph reordering algorithm and the layout-aware multi-head self-attention layer play a crucial role in achieving the best performance.

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Bayesian Segmentation Modeling of Epidemic Growth

Tracking the spread of infectious disease during a pandemic has posed a great challenge to the governments and health sectors on a global scale. To facilitate informed public health decision-making, the concerned parties usually rely on short-term daily and weekly projections generated via predictive modeling. Several deterministic and stochastic epidemiological models, including growth and compartmental models, have been proposed in the literature. These models assume that an epidemic would last over a short duration and the observed cases/deaths would attain a single peak. However, some infectious diseases, such as COVID-19, extend over a longer duration than expected. Moreover, time-varying disease transmission rates due to government interventions have made the observed data multi-modal. To address these challenges, this work proposes stochastic epidemiological models under a unified Bayesian framework augmented by a change-point detection mechanism to account for multiple peaks. The Bayesian framework allows us to incorporate prior knowledge, such as dates of influential policy changes, to predict the change-point locations precisely. We develop a trans-dimensional reversible jump Markov chain Monte Carlo algorithm to sample the posterior distributions of epidemiological parameters while estimating the number of change points and the resulting parameters. The proposed method is evaluated and compared to alternative methods in terms of change-point detection, parameter estimation, and long-term forecasting accuracy on both simulated and COVID-19 data of several major states in the United States.

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Using Persistent Homology Topological Features to Characterize Medical Images: Case Studies on Lung and Brain Cancers

Tumor shape is a key factor that affects tumor growth and metastasis. This paper proposes a topological feature computed by persistent homology to characterize tumor progression from digital pathology and radiology images and examines its effect on the time-to-event data. The proposed topological features are invariant to scale-preserving transformation and can summarize various tumor shape patterns. The topological features are represented in functional space and used as functional predictors in a functional Cox proportional hazards model. The proposed model enables interpretable inference about the association between topological shape features and survival risks. Two case studies are conducted using consecutive 133 lung cancer and 77 brain tumor patients. The results of both studies show that the topological features predict survival prognosis after adjusting clinical variables, and the predicted high-risk groups have worse survival outcomes than the low-risk groups. Also, the topological shape features found to be positively associated with survival hazards are irregular and heterogeneous shape patterns, which are known to be related to tumor progression.

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Domain Randomization-Enhanced Depth Simulation and Restoration for Perceiving and Grasping Specular and Transparent Objects

Commercial depth sensors usually generate noisy and missing depths, especially on specular and transparent objects, which poses critical issues to downstream depth or point cloud-based tasks. To mitigate this problem, we propose a powerful RGBD fusion network, SwinDRNet, for depth restoration. We further propose Domain Randomization-Enhanced Depth Simulation (DREDS) approach to simulate an active stereo depth system using physically based rendering and generate a large-scale synthetic dataset that contains 130K photorealistic RGB images along with their simulated depths carrying realistic sensor noises. To evaluate depth restoration methods, we also curate a real-world dataset, namely STD, that captures 30 cluttered scenes composed of 50 objects with different materials from specular, transparent, to diffuse. Experiments demonstrate that the proposed DREDS dataset bridges the sim-to-real domain gap such that, trained on DREDS, our SwinDRNet can seamlessly generalize to other real depth datasets, e.g. ClearGrasp, and outperform the competing methods on depth restoration with a real-time speed. We further show that our depth restoration effectively boosts the performance of downstream tasks, including category-level pose estimation and grasping tasks. Our data and code are available at https://github.com/PKU-EPIC/DREDS

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A Bayesian Modified Ising Model for Identifying Spatially Variable Genes from Spatial Transcriptomics Data

A recent technology breakthrough in spatial molecular profiling has enabled the comprehensive molecular characterizations of single cells while preserving spatial information. It provides new opportunities to delineate how cells from different origins form tissues with distinctive structures and functions. One immediate question in spatial molecular profiling data analysis is to identify genes whose expressions exhibit spatially correlated patterns, called spatially variable genes. Most current methods to identify spatially variable genes are built upon the geostatistical model with Gaussian process to capture the spatial patterns, which rely on ad hoc kernels that could limit the models' ability to identify complex spatial patterns. In order to overcome this challenge and capture more types of spatial patterns, we introduce a Bayesian approach to identify spatially variable genes via a modified Ising model. The key idea is to use the energy interaction parameter of the Ising model to characterize spatial expression patterns. We use auxiliary variable Markov chain Monte Carlo algorithms to sample from the posterior distribution with an intractable normalizing constant in the model. Simulation studies using both simulated and synthetic data showed that the energy-based modeling approach led to higher accuracy in detecting spatially variable genes than those kernel-based methods. When applied to two real spatial transcriptomics datasets, the proposed method discovered novel spatial patterns that shed light on the biological mechanisms. In summary, the proposed method presents a new perspective for analyzing spatial transcriptomics data.

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Discovering Clinically Meaningful Shape Features for the Analysis of Tumor Pathology Images

With the advanced imaging technology, digital pathology imaging of tumor tissue slides is becoming a routine clinical procedure for cancer diagnosis. This process produces massive imaging data that capture histological details in high resolution. Recent developments in deep-learning methods have enabled us to automatically detect and characterize the tumor regions in pathology images at large scale. From each identified tumor region, we extracted 30 well-defined descriptors that quantify its shape, geometry, and topology. We demonstrated how those descriptor features were associated with patient survival outcome in lung adenocarcinoma patients from the National Lung Screening Trial (n=143). Besides, a descriptor-based prognostic model was developed and validated in an independent patient cohort from The Cancer Genome Atlas Program program (n=318). This study proposes new insights into the relationship between tumor shape, geometrical, and topological features and patient prognosis. We provide software in the form of R code on GitHub: https://github.com/estfernandez/Slide_Image_Segmentation_and_Extraction.

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Bayesian Modeling of Spatial Molecular Profiling Data via Gaussian Process

The location, timing, and abundance of gene expression (both mRNA and proteins) within a tissue define the molecular mechanisms of cell functions. Recent technology breakthroughs in spatial molecular profiling, including imaging-based technologies and sequencing-based technologies, have enabled the comprehensive molecular characterization of single cells while preserving their spatial and morphological contexts. This new bioinformatics scenario calls for effective and robust computational methods to identify genes with spatial patterns. We represent a novel Bayesian hierarchical model to analyze spatial transcriptomics data, with several unique characteristics. It models the zero-inflated and over-dispersed counts by deploying a zero-inflated negative binomial model that greatly increases model stability and robustness. Besides, the Bayesian inference framework allows us to borrow strength in parameter estimation in a de novo fashion. As a result, the proposed model shows competitive performances in accuracy and robustness over existing methods in both simulation studies and two real data applications. The related R/C++ source code is available at https://github.com/Minzhe/BOOST-GP.

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Bayesian Landmark-based Shape Analysis of Tumor Pathology Images

Medical imaging is a form of technology that has revolutionized the medical field in the past century. In addition to radiology imaging of tumor tissues, digital pathology imaging, which captures histological details in high spatial resolution, is fast becoming a routine clinical procedure for cancer diagnosis support and treatment planning. Recent developments in deep-learning methods facilitate the segmentation of tumor regions at almost the cellular level from digital pathology images. The traditional shape features that were developed for characterizing tumor boundary roughness in radiology are not applicable. Reliable statistical approaches to modeling tumor shape in pathology images are in urgent need. In this paper, we consider the problem of modeling a tumor boundary with a closed polygonal chain. A Bayesian landmark-based shape analysis (BayesLASA) model is proposed to partition the polygonal chain into mutually exclusive segments to quantify the boundary roughness piecewise. Our fully Bayesian inference framework provides uncertainty estimates of both the number and locations of landmarks. The BayesLASA outperforms a recently developed landmark detection model for planar elastic curves in terms of accuracy and efficiency. We demonstrate how this model-based analysis can lead to sharper inferences than ordinary approaches through a case study on the 246 pathology images from 143 non-small cell lung cancer patients. The case study shows that the heterogeneity of tumor boundary roughness predicts patient prognosis (p-value < 0.001). This statistical methodology not only presents a new model for characterizing a digitized object's shape features by using its landmarks, but also provides a new perspective for understanding the role of tumor surface in cancer progression.

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Bayesian biclustering for microbial metagenomic sequencing data via multinomial matrix factorization

High-throughput sequencing technology provides unprecedented opportunities to quantitatively explore human gut microbiome and its relation to diseases. Microbiome data are compositional, sparse, noisy, and heterogeneous, which pose serious challenges for statistical modeling. We propose an identifiable Bayesian multinomial matrix factorization model to infer overlapping clusters on both microbes and hosts. The proposed method represents the observed over-dispersed zero-inflated count matrix as Dirichlet-multinomial mixtures on which latent cluster structures are built hierarchically. Under the Bayesian framework, the number of clusters is automatically determined and available information from a taxonomic rank tree of microbes is naturally incorporated, which greatly improves the interpretability of our findings. We demonstrate the utility of the proposed approach by comparing to alternative methods in simulations. An application to a human gut microbiome dataset involving patients with inflammatory bowel disease reveals interesting clusters, which contain bacteria families Bacteroidaceae, Bifidobacteriaceae, Enterobacteriaceae, Fusobacteriaceae, Lachnospiraceae, Ruminococcaceae, Pasteurellaceae, and Porphyromonadaceae that are known to be related to the inflammatory bowel disease and its subtypes according to biological literature. Our findings can help generate potential hypotheses for future investigation of the heterogeneity of the human gut microbiome.

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RCRnorm: An integrated system of random-coefficient hierarchical regression models for normalizing NanoString nCounter data

Formalin-fixed paraffin-embedded (FFPE) samples have great potential for biomarker discovery, retrospective studies and diagnosis or prognosis of diseases. Their application, however, is hindered by the unsatisfactory performance of traditional gene expression profiling techniques on damaged RNAs. NanoString nCounter platform is well suited for profiling of FFPE samples and measures gene expression with high sensitivity which may greatly facilitate realization of scientific and clinical values of FFPE samples. However, methodological development for normalization, a critical step when analyzing this type of data, is far behind. Existing methods designed for the platform use information from different types of internal controls separately and rely on an overly-simplified assumption that expression of housekeeping genes is constant across samples for global scaling. Thus, these methods are not optimized for the nCounter system, not mentioning that they were not developed for FFPE samples. We construct an integrated system of random-coefficient hierarchical regression models to capture main patterns and characteristics observed from NanoString data of FFPE samples and develop a Bayesian approach to estimate parameters and normalize gene expression across samples. Our method, labeled RCRnorm, incorporates information from all aspects of the experimental design and simultaneously removes biases from various sources. It eliminates the unrealistic assumption on housekeeping genes and offers great interpretability. Furthermore, it is applicable to freshly frozen or like samples that can be generally viewed as a reduced case of FFPE samples. Simulation and applications showed the superior performance of RCRnorm.

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A Bayesian Zero-Inflated Negative Binomial Regression Model for the Integrative Analysis of Microbiome Data

Microbiome `omics approaches can reveal intriguing relationships between the human microbiome and certain disease states. Along with the identification of specific bacteria taxa associated with diseases, recent scientific advancements provide mounting evidence that metabolism, genetics and environmental factors can all modulate these microbial effects. However, the current methods for integrating microbiome data and other covariates are severely lacking. Hence, we present an integrative Bayesian zero-inflated negative binomial regression model that can both distinguish differentially abundant taxa with distinct phenotypes and quantify covariate-taxa effects. Our model demonstrates good performance using simulated data. Furthermore, we successfully integrated microbiome taxonomies and metabolomics in two real microbiome datasets to provide biologically interpretable findings. In all, we proposed a novel integrative Bayesian regression model that features bacterial differential abundance analysis and microbiome-covariate effects quantifications, which makes it suitable for general microbiome studies.

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Bayesian Modeling of Microbiome Data for Differential Abundance Analysis

The advances of next-generation sequencing technology have accelerated study of the microbiome and stimulated the high throughput profiling of metagenomes. The large volume of sequenced data has encouraged the rise of various studies for detecting differentially abundant taxonomic features across healthy and diseased populations, with the ultimate goal of deciphering the relationship between the microbiome diversity and health conditions. As the microbiome data are high-dimensional, typically featuring by uneven sampling depth, overdispersion and a huge amount of zeros, these data characteristics often hamper the downstream analysis. Moreover, the taxonomic features are implicitly imposed by the phylogenetic tree structure and often ignored. To overcome these challenges, we propose a Bayesian hierarchical modeling framework for the analysis of microbiome count data for differential abundance analysis. Under this framework, we introduce a bi-level Bayesian hierarchical model that allows a flexible choice of the count generating process, and hyperpriors in the feature selection scheme. We particularly focus on employing a zero-inflated negative binomial model with a Bayesian nonparametric prior model on the bottom level, and applying Gaussian mixture models for differentially abundant taxa detection on the top level. Our method allows for the simultaneous modeling of sample heterogeneity and detecting differentially abundant taxa. We conducted comprehensive simulations and summarized the improved statistical performances of the proposed model. We applied the model in two real microbiome study datasets and successfully identified biologically validated differentially abundant taxa. We hope that the proposed framework and model can facilitate further microbiome studies and elucidate disease etiology.

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A Bayesian Mark Interaction Model for Analysis of Tumor Pathology Images

With the advance of imaging technology, digital pathology imaging of tumor tissue slides is becoming a routine clinical procedure for cancer diagnosis. This process produces massive imaging data that capture histological details in high resolution. Recent developments in deep-learning methods have enabled us to identify and classify individual cells from digital pathology images at large scale. The randomly distributed cells can be considered from a marked point process, where each point is defined by its position and cell type. Reliable statistical approaches to model such marked spatial point patterns can provide new insight into tumor progression and shed light on the biological mechanisms of cancer. In this paper, we consider the problem of modeling spatial correlations among three commonly seen cells (i.e. lymphocyte, stromal, and tumor) observed in tumor pathology images. A novel marking model of marked point processes, with interpretable underlying parameters (some of which are clinically meaningful), is proposed in a Bayesian framework. We use Markov chain Monte Carlo (MCMC) sampling techniques, combined with the double Metropolis-Hastings (DMH) algorithm, to sample from the posterior distribution with an intractable normalizing constant. On the benchmark datasets, we demonstrate how this model-based analysis can lead to sharper inferences than ordinary exploratory analyses. Lastly, we conduct a case study on the pathology images of 188 lung cancer patients from the National Lung Screening Trial. The results show that the spatial correlation between tumor and stromal cells predicts patient prognosis. This statistical methodology not only presents a new model for characterizing spatial correlations in a multi-type spatial point pattern, but also provides a new perspective for understanding the role of cell-cell interactions in cancer progression.

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Oracally Efficient Estimation of Functional-Coefficient Autoregressive Models

Nonlinear autoregressive models are very useful for modeling many natural processes, however, the size of the class of these models is large. Functional-coefficient autoregressive models (FCAR) are useful structures for reducing the size of the class of these models. Although this structure reduces the class of nonlinear models, it is broad enough to include some common time series models as specific cases. A recent development in estimating nonlinear time series data is the spline backfitted kernel (SBK) method. This method combines the computational speed of splines with the asymptotic properties of kernel smoothing. To estimate a component function in the model, all other component functions are pre-estimated with splines and then the difference is taken of the observed time series and the pre-estimates. This difference is then used as pseudo-responses for which kernel smoothing is used to estimate the function of interest. By constructing the estimates in this way, the method does not suffer from the curse of dimensionality. In this paper, we adapt the SBK method to FCAR models.

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Enabling Multi-level Trust in Privacy Preserving Data Mining

Privacy Preserving Data Mining (PPDM) addresses the problem of developing accurate models about aggregated data without access to precise information in individual data record. A widely studied \emph{perturbation-based PPDM} approach introduces random perturbation to individual values to preserve privacy before data is published. Previous solutions of this approach are limited in their tacit assumption of single-level trust on data miners. In this work, we relax this assumption and expand the scope of perturbation-based PPDM to Multi-Level Trust (MLT-PPDM). In our setting, the more trusted a data miner is, the less perturbed copy of the data it can access. Under this setting, a malicious data miner may have access to differently perturbed copies of the same data through various means, and may combine these diverse copies to jointly infer additional information about the original data that the data owner does not intend to release. Preventing such \emph{diversity attacks} is the key challenge of providing MLT-PPDM services. We address this challenge by properly correlating perturbation across copies at different trust levels. We prove that our solution is robust against diversity attacks with respect to our privacy goal. That is, for data miners who have access to an arbitrary collection of the perturbed copies, our solution prevent them from jointly reconstructing the original data more accurately than the best effort using any individual copy in the collection. Our solution allows a data owner to generate perturbed copies of its data for arbitrary trust levels on-demand. This feature offers data owners maximum flexibility.

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