GLDADec: marker-gene guided LDA modeling for bulk gene expression deconvolution.

Inferring cell type proportions from bulk transcriptome data is crucial in immunology and oncology. Here, we introduce guided LDA deconvolution (GLDADec), a bulk deconvolution method that guides topics using cell type-specific marker gene names to estimate topic distributions for each sample. Through benchmarking using blood-derived datasets, we demonstrate its high estimation performance and robustness. Moreover, we apply GLDADec to heterogeneous tissue bulk data and perform comprehensive cell type analysis in a data-driven manner. We show that GLDADec outperforms existing methods in estimation performance and evaluate its biological interpretability by examining enrichment of biological processes for topics. Finally, we apply GLDADec to The Cancer Genome Atlas tumor samples, enabling subtype stratification and survival analysis based on estimated cell type proportions, thus proving its practical utility in clinical settings. This approach, utilizing marker gene names as partial prior information, can be applied to various scenarios for bulk data deconvolution. GLDADec is available as an open-source Python package at https://github.com/mizuno-group/GLDADec.

A Bayesian nonparametric approach for multiple mediators with applications in mental health studies.

Mediation analysis with contemporaneously observed multiple mediators is a significant area of causal inference. Recent approaches for multiple mediators are often based on parametric models and thus may suffer from model misspecification. Also, much of the existing literature either only allow estimation of the joint mediation effect or estimate the joint mediation effect just as the sum of individual mediator effects, ignoring the interaction among the mediators. In this article, we propose a novel Bayesian nonparametric method that overcomes the two aforementioned drawbacks. We model the joint distribution of the observed data (outcome, mediators, treatment, and confounders) flexibly using an enriched Dirichlet process mixture with three levels. We use standardization (g-computation) to compute all possible mediation effects, including pairwise and all other possible interaction among the mediators. We thoroughly explore our method via simulations and apply our method to a mental health data from Wisconsin Longitudinal Study, where we estimate how the effect of births from unintended pregnancies on later life mental depression (CES-D) among the mothers is mediated through lack of self-acceptance and autonomy, employment instability, lack of social participation, and increased family stress. Our method identified significant individual mediators, along with some significant pairwise effects.

A new approach to describe the taxonomic structure of microbiome and its application to assess the relationship between microbial niches.

BACKGROUND: Data from microbiomes from multiple niches is often collected, but methods to analyse these often ignore associations between niches. One interesting case is that of the oral microbiome. Its composition is receiving increasing attention due to reports on its associations with general health. While the oral cavity includes different niches, multi-niche microbiome data analysis is conducted using a single niche at a time and, therefore, ignores other niches that could act as confounding variables. Understanding the interaction between niches would assist interpretation of the results, and help improve our understanding of multi-niche microbiomes. METHODS: In this study, we used a machine learning technique called latent Dirichlet allocation (LDA) on two microbiome datasets consisting of several niches. LDA was used on both individual niches and all niches simultaneously. On individual niches, LDA was used to decompose each niche into bacterial sub-communities unveiling their taxonomic structure. These sub-communities were then used to assess the relationship between microbial niches using the global test. On all niches simultaneously, LDA allowed us to extract meaningful microbial patterns. Sets of co-occurring operational taxonomic units (OTUs) comprising those patterns were then used to predict the original location of each sample. RESULTS: Our approach showed that the per-niche sub-communities displayed a strong association between supragingival plaque and saliva, as well as between the anterior and posterior tongue. In addition, the LDA-derived microbial signatures were able to predict the original sample niche illustrating the meaningfulness of our sub-communities. For the multi-niche oral microbiome dataset we had an overall accuracy of 76%, and per-niche sensitivity of up to 83%. Finally, for a second multi-niche microbiome dataset from the entire body, microbial niches from the oral cavity displayed stronger associations to each other than with those from other parts of the body, such as niches within the vagina and the skin. CONCLUSION: Our LDA-based approach produces sets of co-occurring taxa that can describe niche composition. LDA-derived microbial signatures can also be instrumental in summarizing microbiome data, for both descriptions as well as prediction.

A Bayesian nonparametric approach to correct for underreporting in count data.

We propose a nonparametric compound Poisson model for underreported count data that introduces a latent clustering structure for the reporting probabilities. The latter are estimated with the model's parameters based on experts' opinion and exploiting a proxy for the reporting process. The proposed model is used to estimate the prevalence of chronic kidney disease in Apulia, Italy, based on a unique statistical database covering information on m = 258 municipalities obtained by integrating multisource register information. Accurate prevalence estimates are needed for monitoring, surveillance, and management purposes; yet, counts are deemed to be considerably underreported, especially in some areas of Apulia, one of the most deprived and heterogeneous regions in Italy. Our results agree with previous findings and highlight interesting geographical patterns of the disease. We compare our model to existing approaches in the literature using simulated as well as real data on early neonatal mortality risk in Brazil, described in previous research: the proposed approach proves to be accurate and particularly suitable when partial information about data quality is available.

Spatial Difference Boundary Detection for Multiple Outcomes Using Bayesian Disease Mapping.

Regional aggregates of health outcomes over delineated administrative units (e.g., states, counties, and zip codes), or areal units, are widely used by epidemiologists to map mortality or incidence rates and capture geographic variation. To capture health disparities over regions, we seek "difference boundaries" that separate neighboring regions with significantly different spatial effects. Matters are more challenging with multiple outcomes over each unit, where we capture dependence among diseases as well as across the areal units. Here, we address multivariate difference boundary detection for correlated diseases. We formulate the problem in terms of Bayesian pairwise multiple comparisons and seek the posterior probabilities of neighboring spatial effects being different. To achieve this, we endow the spatial random effects with a discrete probability law using a class of multivariate areally referenced Dirichlet process models that accommodate spatial and interdisease dependence. We evaluate our method through simulation studies and detect difference boundaries for multiple cancers using data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.

Hypoconulid loss in cercopithecins: Functional and developmental considerations.

Cercopithecins differ from papionins in lacking a M3 hypoconulid. Although this loss may be related to dietary differences, the functional and developmental ramifications of hypoconulid loss are currently unclear. The following makes use of dental topographic analysis to quantify shape variation in a sample of cercopithecin M3s, as well as in a sample of Macaca, which has a hypoconulid. To help understand the consequences of hypoconulid loss, Macaca M3s were virtually cropped to remove the hypoconulid and were also subjected to dental topographic analysis. The patterning cascade model and the inhibitory cascade model attempt to explain variation in cusp pattern and molar proportions, respectively. These models have both previously been used to explain patterns of variation in cercopithecines, but have not been examined in the context of hypoconulid loss. For example, previous work suggests that earlier developing cusps impact the development of later developing cusps (i.e., the hypoconulid) and that cercopithecines do not conform to the predictions of the inhibitory cascade model in that the size of the molars is not linear moving distally. Results of the current study suggest that the loss of the hypoconulid is associated with a reduction in dental topography among cercopithecins, which is potentially related to diet, although the connection to diet is not necessarily clear. Results also suggest that the loss of the hypoconulid can be explained by the patterning cascade model, and that hypoconulid loss explains the apparent lack of support for the inhibitory cascade model among cercopithecines. These findings highlight the importance of a holistic approach to studying variation in molar proportions and developmental models.

Confounder-dependent Bayesian mixture model: Characterizing heterogeneity of causal effects in air pollution epidemiology.

Several epidemiological studies have provided evidence that long-term exposure to fine particulate matter (pm2.5) increases mortality rate. Furthermore, some population characteristics (e.g., age, race, and socioeconomic status) might play a crucial role in understanding vulnerability to air pollution. To inform policy, it is necessary to identify groups of the population that are more or less vulnerable to air pollution. In causal inference literature, the group average treatment effect (GATE) is a distinctive facet of the conditional average treatment effect. This widely employed metric serves to characterize the heterogeneity of a treatment effect based on some population characteristics. In this paper, we introduce a novel Confounder-Dependent Bayesian Mixture Model (CDBMM) to characterize causal effect heterogeneity. More specifically, our method leverages the flexibility of the dependent Dirichlet process to model the distribution of the potential outcomes conditionally to the covariates and the treatment levels, thus enabling us to: (i) identify heterogeneous and mutually exclusive population groups defined by similar GATEs in a data-driven way, and (ii) estimate and characterize the causal effects within each of the identified groups. Through simulations, we demonstrate the effectiveness of our method in uncovering key insights about treatment effects heterogeneity. We apply our method to claims data from Medicare enrollees in Texas. We found six mutually exclusive groups where the causal effects of pm2.5 on mortality rate are heterogeneous.

Bayesian hierarchical profile regression for binary covariates.

Dysphagia, a common result of other medical conditions, is caused by malfunctions in swallowing physiology resulting in difficulty eating and drinking. The Modified Barium Swallow Study (MBSS), the most commonly used diagnostic tool for evaluating dysphagia, can be assessed using the Modified Barium Swallow Impairment Profile (MBSImP™). The MBSImP assessment tool consists of a hierarchical grouped data structure with multiple domains, a set of components within each domain which characterize specific swallowing physiologies, and a set of tasks scored on a discrete scale within each component. We lack sophisticated approaches to extract patterns of physiologic swallowing impairment from the MBSImP task scores within a component while still recognizing the nested structure of components within a domain. We propose a Bayesian hierarchical profile regression model, which uses a Bayesian profile regression model in conjunction with a hierarchical Dirichlet process mixture model to (1) cluster subjects into impairment profile patterns while respecting the hierarchical grouped data structure of the MBSImP, and (2) simultaneously determine associations between latent profile cluster membership for all components and the outcome of dysphagia severity. We apply our approach to a cohort of patients referred for an MBSS and assessed using the MBSImP. Our research results can be used to inform appropriate intervention strategies, and provide tools for clinicians to make better multidimensional management and treatment decisions for patients with dysphagia.

Joint modeling of association networks and longitudinal biomarkers: An application to childhood obesity.

The prevalence of chronic non-communicable diseases such as obesity has noticeably increased in the last decade. The study of these diseases in early life is of paramount importance in determining their course in adult life and in supporting clinical interventions. Recently, attention has been drawn to approaches that study the alteration of metabolic pathways in obese children. In this work, we propose a novel joint modeling approach for the analysis of growth biomarkers and metabolite associations, to unveil metabolic pathways related to childhood obesity. Within a Bayesian framework, we flexibly model the temporal evolution of growth trajectories and metabolic associations through the specification of a joint nonparametric random effect distribution, with the main goal of clustering subjects, thus identifying risk sub-groups. Growth profiles as well as patterns of metabolic associations determine the clustering structure. Inclusion of risk factors is straightforward through the specification of a regression term. We demonstrate the proposed approach on data from the Growing Up in Singapore Towards healthy Outcomes cohort study, based in Singapore. Posterior inference is obtained via a tailored MCMC algorithm, involving a nonparametric prior with mixed support. Our analysis has identified potential key pathways in obese children that allow for the exploration of possible molecular mechanisms associated with childhood obesity.

Assessing the needs of patients with breast cancer and their families across various treatment phases using a Latent Dirichlet Allocation model: a text-mining approach to online health communities.

PURPOSE: This study aimed to assess the different needs of patients with breast cancer and their families in online health communities at different treatment phases using a Latent Dirichlet Allocation (LDA) model. METHODS: Using Python, breast cancer-related posts were collected from two online health communities: patient-to-patient and patient-to-doctor. After data cleaning, eligible posts were categorized based on the treatment phase. Subsequently, an LDA model identifying the distinct need-related topics for each phase of treatment, including data preprocessing and LDA topic modeling, was established. Additionally, the demographic and interactive features of the posts were manually analyzed. RESULTS: We collected 84,043 posts, of which 9504 posts were included after data cleaning. Early diagnosis and rehabilitation treatment phases had the highest and lowest number of posts, respectively. LDA identified 11 topics: three in the initial diagnosis phase and two in each of the remaining treatment phases. The topics included disease outcomes, diagnosis analysis, treatment information, and emotional support in the initial diagnosis phase; surgical options and outcomes, postoperative care, and treatment planning in the perioperative treatment phase; treatment options and costs, side effects management, and disease prognosis assessment in the non-operative treatment phase; diagnosis and treatment options, disease prognosis, and emotional support in the relapse and metastasis treatment phase; and follow-up and recurrence concerns, physical symptoms, and lifestyle adjustments in the rehabilitation treatment phase. CONCLUSION: The needs of patients with breast cancer and their families differ across various phases of cancer therapy. Therefore, specific information or emotional assistance should be tailored to each phase of treatment based on the unique needs of patients and their families.

Using Topic Modeling to Understand Patients' and Caregivers' Perspectives About Left Ventricular Assist Device: Thematic Analysis.

BACKGROUND: Heart failure (HF) is a significant global clinical and public health challenge, impacting 64.3 million individuals worldwide. To address the scarcity of donor organs, left ventricular assist device (LVAD) implantation has become a crucial intervention for managing end-stage HF, serving as a bridge to heart transplantation or as a destination therapy. Web-based health forums, such as MyLVAD.com, play a vital role as trusted sources of information for individuals with HF symptoms and their caregivers. OBJECTIVE: We aim to uncover the latent topics within the posts shared by users on the MyLVAD.com website. METHODS: Using the latent Dirichlet allocation algorithm and a visualization tool, our objective was to uncover latent topics within the posts shared on the MyLVAD.com website. Through the application of topic modeling techniques, we analyzed 459 posts authored by recipients of LVAD and their family members from 2015 to 2023. RESULTS: This study unveiled 5 prominent themes of concern among patients with LVAD and their family members. These themes included family support (39.5% weight value), encompassing subthemes such as family caregiving roles and emotional or practical support; clothing (23.9% weight value), with subthemes related to comfort, normalcy, and functionality; infection (18.2% weight value), covering driveline infections, prevention, and care; power (12% weight value), involving challenges associated with power dependency; and self-care maintenance, monitoring, and management (6.3% weight value), which included subthemes such as blood tests, monitoring, alarms, and device management. CONCLUSIONS: These findings contribute to a better understanding of the experiences and needs of patients implanted with LVAD, providing valuable insights for health care professionals to offer tailored support and care. By using latent Dirichlet allocation to analyze posts from the MyLVAD.com forum, this study sheds light on key topics discussed by users, facilitating improved patient care and enhanced patient-provider communication.

Temporal topic model for clinical pathway mining from electronic medical records.

BACKGROUND: In recent years, the discovery of clinical pathways (CPs) from electronic medical records (EMRs) data has received increasing attention because it can directly support clinical doctors with explicit treatment knowledge, which is one of the key challenges in the development of intelligent healthcare services. However, the existing work has focused on topic probabilistic models, which usually produce treatment patterns with similar treatment activities, and such discovered treatment patterns do not take into account the temporal process of patient treatment which does not meet the needs of practical medical applications. METHODS: Based on the assumption that CPs can be derived from the data of EMRs which usually record the treatment process of patients, this paper proposes a new CPs mining method from EMRs, an extended form of the traditional topic model - the temporal topic model (TTM). The method can capture the treatment topics and the corresponding treatment timestamps for each treatment day. RESULTS: Experimental research conducted on a real-world dataset of patients' hospitalization processes, and the achieved results demonstrate the applicability and usefulness of the proposed methodology for CPs mining. Compared to existing benchmarks, our model shows significant improvement and robustness. CONCLUSION: Our TTM provides a more competitive way to mine potential CPs considering the temporal features of the EMR data, providing a very prospective tool to support clinical diagnostic decisions.

Dirichlet process mixture models to impute missing predictor data in counterfactual prediction models: an application to predict optimal type 2 diabetes therapy.

BACKGROUND: The handling of missing data is a challenge for inference and regression modelling. A particular challenge is dealing with missing predictor information, particularly when trying to build and make predictions from models for use in clinical practice. METHODS: We utilise a flexible Bayesian approach for handling missing predictor information in regression models. This provides practitioners with full posterior predictive distributions for both the missing predictor information (conditional on the observed predictors) and the outcome-of-interest. We apply this approach to a previously proposed counterfactual treatment selection model for type 2 diabetes second-line therapies. Our approach combines a regression model and a Dirichlet process mixture model (DPMM), where the former defines the treatment selection model, and the latter provides a flexible way to model the joint distribution of the predictors. RESULTS: We show that DPMMs can model complex relationships between predictor variables and can provide powerful means of fitting models to incomplete data (under missing-completely-at-random and missing-at-random assumptions). This framework ensures that the posterior distribution for the parameters and the conditional average treatment effect estimates automatically reflect the additional uncertainties associated with missing data due to the hierarchical model structure. We also demonstrate that in the presence of multiple missing predictors, the DPMM model can be used to explore which variable(s), if collected, could provide the most additional information about the likely outcome. CONCLUSIONS: When developing clinical prediction models, DPMMs offer a flexible way to model complex covariate structures and handle missing predictor information. DPMM-based counterfactual prediction models can also provide additional information to support clinical decision-making, including allowing predictions with appropriate uncertainty to be made for individuals with incomplete predictor data.

Shrinkage priors for isotonic probability vectors and binary data modeling, with applications to dose-response modeling.

Motivated by the need to model dose-response or dose-toxicity curves in clinical trials, we develop a new horseshoe-based prior for Bayesian isotonic regression modeling a binary outcome against an ordered categorical predictor, where the probability of the outcome is assumed to be monotonically non-decreasing with the predictor. The set of differences between outcome probabilities in consecutive categories of the predictor is equipped with a multivariate prior having support over simplex. The Dirichlet distribution, which can be derived from a normalized sum of independent gamma-distributed random variables, is a natural choice of prior, but using mathematical and simulation-based arguments, we show that the resulting posterior is prone to underflow and other numerical instabilities, even under simple data configurations. We propose an alternative prior based on horseshoe-type shrinkage that is numerically more stable. We show that this horseshoe-based prior is not subject to the numerical instability seen in the Dirichlet/gamma-based prior and that the horseshoe-based posterior can estimate the underlying true curve more efficiently than the Dirichlet-based one. We demonstrate the use of this prior in a model predicting the occurrence of radiation-induced lung toxicity in lung cancer patients as a function of dose delivered to normal lung tissue. Our methodology is implemented in the R package isotonicBayes and therefore suitable for use in the design of dose-finding studies or other dose-response modeling contexts.

The circular economy through the prism of machine learning and the YouTube video media platform.

The transition to a Circular Economy (CE) is rapidly gaining ground across countries and industries. It is the means of achieving more sustainable development by adopting innovative environmentally friendly strategies and saving primary resources. There are several studies indicating the increasing public and corporate interest in the CE but still remain limited in terms of the multitude and utilization of social media data. This work aims to shed light on the most common topics discussed on the YouTube platform, related to the CE. For this reason, we selected 17 videos including the term "Circular Economy" since these have been the most relevant with a sufficient number of comments and views. The model identified two main topics referring to "Sustainable industry and environmental responsibility" and "Circular Economy and resource management" which is a strong indicator of the people's interest in the utilization of resources alongside industrial and corporate activities. The two-topic configuration presented the highest coherence score; however, five and ten-topic configurations have been deployed since there was no extreme differentiation in the model's performance, which could provide more detailed insights. This work's innovation lies in utilizing Machine Learning techniques and social media data to unravel CE's debates.

Bayesian Non-Parametric Inference for Multivariate Peaks-over-Threshold Models.

We consider a constructive definition of the multivariate Pareto that factorizes the random vector into a radial component and an independent angular component. The former follows a univariate Pareto distribution, and the latter is defined on the surface of the positive orthant of the infinity norm unit hypercube. We propose a method for inferring the distribution of the angular component by identifying its support as the limit of the positive orthant of the unit p-norm spheres and introduce a projected gamma family of distributions defined through the normalization of a vector of independent random gammas to the space. This serves to construct a flexible family of distributions obtained as a Dirichlet process mixture of projected gammas. For model assessment, we discuss scoring methods appropriate to distributions on the unit hypercube. In particular, working with the energy score criterion, we develop a kernel metric that produces a proper scoring rule and presents a simulation study to compare different modeling choices using the proposed metric. Using our approach, we describe the dependence structure of extreme values in the integrated vapor transport (IVT), data describing the flow of atmospheric moisture along the coast of California. We find clear but heterogeneous geographical dependence.

Dementia Knowledge in Chinese Newspapers (2005-2020): A Topic Modeling Analysis.

How public policies convey dementia is an important source of the public's understanding of dementia, and newspapers are critical to depicting and disseminating this information to the public. The present study used topic modeling strategies to analyze Chinese newspaper portrayals of dementia from 2005 to 2020 to trace changes in key areas of dementia knowledge in relevant policies. Using WiseNews, the largest Chinese media database, we chose 45 newspapers from mainland China and identified 12,719 articles related to dementia. Using latent Dirichlet allocation (LDA), we performed a topic modeling analysis and identified the six most prevalent topics on dementia across articles: lifestyle recommendations, neighborhood life, foundational scientific research, celebrity and media portrayals, dementia caregiving, and pharmaceutical innovations - all related to the dementia knowledge scale's four dimensions. Findings suggest a steady increase in the number of articles on dementia caregiving and a decline in lifestyle recommendations from 2005 to 2020. However, newspapers continued to stigmatize aging by regularly co-depicting dementia and old age and by using biased terminology. Among the first to investigate dementia's portrayals in mainland Chinese newspapers, this study illuminates the need for expanding mass media campaigns to raise the country's dementia knowledge to foster a dementia-inclusive society.

Latent dirichlet allocation for double clustering (LDA-DC): discovering patients phenotypes and cell populations within a single Bayesian framework.

BACKGROUND: Current clinical routines rely more and more on "omics" data such as flow cytometry data from host and microbiota. Cohorts variability in addition to patients' heterogeneity and huge dimensions make it difficult to understand underlying structure of the data and decipher pathologies. Patients stratification and diagnostics from such complex data are extremely challenging. There is an acute need to develop novel statistical machine learning methods that are robust with respect to the data heterogeneity, efficient from the computational viewpoint, and can be understood by human experts. RESULTS: We propose a novel approach to stratify cell-based observations within a single probabilistic framework, i.e., to extract meaningful phenotypes from both patients and cells data simultaneously. We define this problem as a double clustering problem that we tackle with the proposed approach. Our method is a practical extension of the Latent Dirichlet Allocation and is used for the Double Clustering task (LDA-DC). We first validate the method on artificial datasets, then we apply our method to two real problems of patients stratification based on cytometry and microbiota data. We observe that the LDA-DC returns clusters of patients and also clusters of cells related to patients' conditions. We also construct a graphical representation of the results that can be easily understood by humans and are, therefore, of a big help for experts involved in pre-clinical research.

A Bayesian nonparametric model for classification of longitudinal profiles.

Across several medical fields, developing an approach for disease classification is an important challenge. The usual procedure is to fit a model for the longitudinal response in the healthy population, a different model for the longitudinal response in the diseased population, and then apply Bayes' theorem to obtain disease probabilities given the responses. Unfortunately, when substantial heterogeneity exists within each population, this type of Bayes classification may perform poorly. In this article, we develop a new approach by fitting a Bayesian nonparametric model for the joint outcome of disease status and longitudinal response, and then we perform classification through the clustering induced by the Dirichlet process. This approach is highly flexible and allows for multiple subpopulations of healthy, diseased, and possibly mixed membership. In addition, we introduce an Markov chain Monte Carlo sampling scheme that facilitates the assessment of the inference and prediction capabilities of our model. Finally, we demonstrate the method by predicting pregnancy outcomes using longitudinal profiles on the human chorionic gonadotropin beta subunit hormone levels in a sample of Chilean women being treated with assisted reproductive therapy.

Bayesian sparse heritability analysis with high-dimensional neuroimaging phenotypes.

Heritability analysis plays a central role in quantitative genetics to describe genetic contribution to human complex traits and prioritize downstream analyses under large-scale phenotypes. Existing works largely focus on modeling single phenotype and currently available multivariate phenotypic methods often suffer from scaling and interpretation. In this article, motivated by understanding how genetic underpinning impacts human brain variation, we develop an integrative Bayesian heritability analysis to jointly estimate heritabilities for high-dimensional neuroimaging traits. To induce sparsity and incorporate brain anatomical configuration, we impose hierarchical selection among both regional and local measurements based on brain structural network and voxel dependence. We also use a nonparametric Dirichlet process mixture model to realize grouping among single nucleotide polymorphism-associated phenotypic variations, providing biological plausibility. Through extensive simulations, we show the proposed method outperforms existing ones in heritability estimation and heritable traits selection under various scenarios. We finally apply the method to two large-scale imaging genetics datasets: the Alzheimer's Disease Neuroimaging Initiative and United Kingdom Biobank and show biologically meaningful results.