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Jacqueline R. Starr

Publications and source records attributed to Jacqueline R. Starr.

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A Bayesian Multivariate Spatial Point Pattern Model: Application to Oral Microbiome FISH Image Data

Advances in cellular imaging technologies, especially those based on fluorescence in situ hybridization (FISH) now allow detailed visualization of the spatial organization of human or bacterial cells. Quantifying this spatial organization is crucial for understanding the function of multicellular tissues or biofilms, with implications for human health and disease. To address the need for better methods to achieve such quantification, we propose a flexible multivariate point process model that characterizes and estimates complex spatial interactions among multiple cell types. The proposed Bayesian framework is appealing due to its unified estimation process and the ability to directly quantify uncertainty in key estimates of interest, such as those of inter-type correlation and the proportion of variance due to inter-type relationships. To ensure stable and interpretable estimation, we consider shrinkage priors for coefficients associated with latent processes. Model selection and comparison are conducted by using a deviance information criterion designed for models with latent variables, effectively balancing the risk of overfitting with that of oversimplifying key quantities. Furthermore, we develop a hierarchical modeling approach to integrate multiple image-specific estimates from a given subject, allowing inference at both the global and subject-specific levels. We apply the proposed method to microbial biofilm image data from the human tongue dorsum and find that specific taxon pairs, such as Streptococcus mitis-Streptococcus salivarius and Streptococcus mitis-Veillonella, exhibit strong positive spatial correlations, while others, such as Actinomyces-Rothia, show slight negative correlations. For most of the taxa, a substantial portion of spatial variance can be attributed to inter-taxon relationships.

stat.ME

Inference for Log-Gaussian Cox Point Processes using Bayesian Deep Learning: Application to Human Oral Microbiome Image Data

It is common in nature to see aggregation of objects in space. Exploring the mechanism associated with the locations of such clustered observations can be essential to understanding the phenomenon, such as the source of spatial heterogeneity, or comparison to other event generating processes in the same domain. Log-Gaussian Cox processes (LGCPs) represent an important class of models for quantifying aggregation in a spatial point pattern. However, implementing likelihood-based Bayesian inference for such models presents many computational challenges, particularly in high dimensions. In this paper, we propose a novel likelihood-free inference approach for LGCPs using the recently developed BayesFlow approach, where invertible neural networks are employed to approximate the posterior distribution of the parameters of interest. BayesFlow is a neural simulation-based method based on "amortized" posterior estimation. That is, after an initial training procedure, fast feed-forward operations allow rapid posterior inference for any data within the same model family. Comprehensive numerical studies validate the reliability of the framework and show that BayesFlow achieves substantial computational gain in repeated application, especially for two-dimensional LGCPs. We demonstrate the utility and robustness of the method by applying it to two distinct oral microbial biofilm images.

stat.ME

Multivariate cluster point process to quantify and explore multi-entity configurations: Application to biofilm image data

Clusters of similar or dissimilar objects are encountered in many fields. Frequently used approaches treat the central object of each cluster as latent. Yet, often objects of one or more types cluster around objects of another type. Such arrangements are common in biomedical images of cells, in which nearby cell types likely interact. Quantifying spatial relationships may elucidate biological mechanisms. Parent-offspring statistical frameworks can be usefully applied even when central objects (parents) differ from peripheral ones (offspring). We propose the novel multivariate cluster point process (MCPP) to quantify multi-object (e.g., multi-cellular) arrangements. Unlike commonly used approaches, the MCPP exploits locations of the central parent object in clusters. It accounts for possibly multilayered, multivariate clustering. The model formulation requires specification of which object types function as cluster centers and which reside peripherally. If such information is unknown, the relative roles of object types may be explored by comparing fit of different models via the deviance information criterion (DIC). In simulated data, we compared DIC of a series of models; the MCPP correctly identified simulated relationships. It also produced more accurate and precise parameter estimates than the classical univariate Neyman-Scott process model. We also used the MCPP to quantify proposed configurations and explore new ones in human dental plaque biofilm image data. MCPP models quantified simultaneous clustering of Streptococcus and Porphyromonas around Corynebacterium and of Pasteurellaceae around Streptococcus and successfully captured hypothesized structures for all taxa. Further exploration suggested the presence of clustering between Fusobacterium and Leptotrichia, a previously unreported relationship.

stat.AP

Bayesian Variable Selection for Multivariate Zero-Inflated Models: Application to Microbiome Count Data

Microorganisms play critical roles in human health and disease. It is well known that microbes live in diverse communities in which they interact synergistically or antagonistically. Thus for estimating microbial associations with clinical covariates, multivariate statistical models are preferred. Multivariate models allow one to estimate and exploit complex interdependencies among multiple taxa, yielding more powerful tests of exposure or treatment effects than application of taxon-specific univariate analyses. In addition, the analysis of microbial count data requires special attention because data commonly exhibit zero inflation. To meet these needs, we developed a Bayesian variable selection model for multivariate count data with excess zeros that incorporates information on the covariance structure of the outcomes (counts for multiple taxa), while estimating associations with the mean levels of these outcomes. Although there has been a great deal of effort in zero-inflated models for longitudinal data, little attention has been given to high-dimensional multivariate zero-inflated data modeled via a general correlation structure. Through simulation, we compared performance of the proposed method to that of existing univariate approaches, for both the binary and count parts of the model. When outcomes were correlated the proposed variable selection method maintained type I error while boosting the ability to identify true associations in the binary component of the model. For the count part of the model, in some scenarios the the univariate method had higher power than the multivariate approach. This higher power was at a cost of a highly inflated false discovery rate not observed with the proposed multivariate method. We applied the approach to oral microbiome data from the Pediatric HIV/AIDS Cohort Oral Health Study and identified five species (of 44) associated with HIV infection.

stat.AP