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Cancer is a heterogeneous disease. Finite mixture of regression (FMR)—as an important heterogeneity analysis technique when an outcome variable is present—has been extensively employed in cancer research, revealing important differences in the associations between a cancer outcome/phenotype and covariates. Cancer FMR analysis has been based on clinical, demographic, and omics variables. A relatively recent and alternative source of data comes from histopathological images. Histopathological images have been long used for cancer diagnosis and staging. Recently, it has been shown that high-dimensional histopathological image features, which are extracted using automated digital image processing pipelines, are effective for modeling cancer outcomes/phenotypes. Histopathological imaging–environment interaction analysis has been further developed to expand the scope of cancer modeling and histopathological imaging-based analysis. Motivated by the significance of cancer FMR analysis and a still strong demand for more effective methods, in this article, we take the natural next step and conduct cancer FMR analysis based on models that incorporate low-dimensional clinical/demographic/environmental variables, high-dimensional imaging features, as well as their interactions. Complementary to many of the existing studies, we develop a Bayesian approach for accommodating high dimensionality, screening out noises, identifying signals, and respecting the “main effects, interactions” variable selection hierarchy. An effective computational algorithm is developed, and simulation shows advantageous performance of the proposed approach. The analysis of The Cancer Genome Atlas data on lung squamous cell cancer leads to interesting findings different from the alternative approaches.

 

Multiple types of molecular (genetic, genomic, epigenetic, etc.) measurements, environmental risk factors, and their interactions have been found to contribute to the outcomes and phenotypes of complex diseases. In each of the previous studies, only the interactions between one type of molecular measurement and environmental risk factors have been analyzed. In recent biomedical studies, multidimensional profiling, in which data from multiple types of molecular measurements are collected from the same subjects, is becoming popular. A myriad of recent studies have shown that collectively analyzing multiple types of molecular measurements is not only biologically sensible but also leads to improved estimation and prediction. In this study, we conduct an M–E interaction analysis, with M standing for multidimensional molecular measurements and E standing for environmental risk factors. This can accommodate multiple types of molecular measurements and sufficiently account for their overlapping as well as independent information. Extensive simulation shows that it outperforms several closely related alternatives. In the analysis of TCGA (The Cancer Genome Atlas) data on lung adenocarcinoma and cutaneous melanoma, we make some stable biological findings and achieve stable prediction.

 

In cancer research, supervised heterogeneity analysis has important implications. Such analysis has been traditionally based on clinical/demographic/molecular variables. Recently, histopathological imaging features, which are generated as a byproduct of biopsy, have been shown as effective for modeling cancer outcomes, and a handful of supervised heterogeneity analysis has been conducted based on such features. There are two types of histopathological imaging features, which are extracted based on specific biological knowledge and using automated imaging processing software, respectively. Usingbothtypes of histopathological imaging features, our goal is to conduct the first supervised cancer heterogeneity analysisthat satisfies a hierarchical structure. That is, the first type of imaging features defines a rough structure, and the second type defines a nested and more refined structure. A penalization approach is developed, which has been motivated by but differs significantly from penalized fusion and sparse group penalization. It has satisfactory statistical and numerical properties. In the analysis of lung adenocarcinoma data, it identifies a heterogeneity structure significantly different from the alternatives and has satisfactory prediction and stability performance.

 

Heterogeneity is a hallmark of cancer, diabetes, cardiovascular diseases, and many other complex diseases. This study has been partly motivated by the unsupervised heterogeneity analysis for complex diseases based on molecular and imaging data, for which, network‐based analysis, by accommodating the interconnections among variables, can be more informative than that limited to mean, variance, and other simple distributional properties. In the literature, there has been very limited research on network‐based heterogeneity analysis, and a common limitation shared by the existing techniques is that the number of subgroups needs to be specified a priori or in an ad hoc manner. In this article, we develop a penalized fusion approach for heterogeneity analysis based on the Gaussian graphical model. It applies penalization to the mean and precision matrix parameters to generate regularized and interpretable estimates. More importantly, a fusion penalty is imposed to “automatedly” determine the number of subgroups and generate more concise, reliable, and interpretable estimation. Consistency properties are rigorously established, and an effective computational algorithm is developed. The heterogeneity analysis of non‐small‐cell lung cancer based on single‐cell gene expression data of the Wnt pathway and that of lung adenocarcinoma based on histopathological imaging data not only demonstrate the practical applicability of the proposed approach but also lead to interesting new findings.

 

E-healthcare has been envisaged as a major component of the infrastructure of modern healthcare, and has been developing rapidly in China. For healthcare, news media can play an important role in raising public interest and utilization of a particular service and complicating (and, perhaps clouding) debate on public health policy issues. We conducted a linguistic analysis of news reports from January 2015 to June 2021 related to E-healthcare in mainland China, using a heterogeneous graphical modeling approach. This approach can simultaneously cluster the datasets and estimate the conditional dependence relationships of keywords. It was found that there were eight phases of media coverage. The focuses and main topics of media coverage were extracted based on the network hub and module detection. The temporal patterns of media reports were found to be mostly consistent with the policy trend. Specifically, in the policy embryonic period (2015–2016), two phases were obtained, industry management was the main topic, and policy and regulation were the focuses of media coverage. In the policy development period (2017–2019), four phases were discovered. All the four main topics, namely industry development, health care, financial market, and industry management, were present. In 2017 Q3–2017 Q4, the major focuses of media coverage included social security, healthcare and reform, and others. In 2018 Q1, industry regulation and finance became the focuses. In the policy outbreak period (2020–), two phases were discovered. Financial market and industry management were the main topics. Medical insurance and healthcare for the elderly became the focuses. This analysis can offer insights into how the media responds to public policy for E-healthcare, which can be valuable for the government, public health practitioners, health care industry investors, and others. 

Abstract Studies on the conditional relationships between PM2.5 concentrations among different regions are of great interest for the joint prevention and control of air pollution. Because of seasonal changes in atmospheric conditions, spatial patterns of PM2.5 may differ throughout the year. Additionally, concentration data are both non-negative and non-Gaussian. These data features pose significant challenges to existing methods. This study proposes a heterogeneous graphical model for non-negative and non-Gaussian data via the score matching loss. The proposed method simultaneously clusters multiple datasets and estimates a graph for variables with complex properties in each cluster. Furthermore, our model involves a network that indicate similarity among datasets, and this network can have additional applications. In simulation studies, the proposed method outperforms competing alternatives in both clustering and edge identification. We also analyse the PM2.5 concentrations' spatial correlations in Taiwan's regions using data obtained in year 2019 from 67 air-quality monitoring stations. The 12 months are clustered into four groups: January–March, April, May–September and October–December, and the corresponding graphs have 153, 57, 86 and 167 edges respectively. The results show obvious seasonality, which is consistent with the meteorological literature. Geographically, the PM2.5 concentrations of north and south Taiwan regions correlate more respectively. These results can provide valuable information for developing joint air-quality control strategies.