Identification of cancer subtypes plays an important role in revealing useful insights into disease pathogenesis and advancing personalized therapy. The recent development of high-throughput sequencing technologies has enabled the rapid collection of multi-platform genomic data (e.g., gene expression, miRNA expression, and DNA methylation) for the same set of tumor samples. Although numerous integrative clustering approaches have been developed to analyze cancer data, few of them are particularly designed to exploit both deep intrinsic statistical properties of each input modality and complex cross-modality correlations among multi-platform input data. In this paper, we propose a new machine learning model, called multimodal deep belief network (DBN), to cluster cancer patients from multi-platform observation data. In our integrative clustering framework, relationships among inherent features of each single modality are first encoded into multiple layers of hidden variables, and then a joint latent model is employed to fuse common features derived from multiple input modalities. A practical learning algorithm, called contrastive divergence (CD), is applied to infer the parameters of our multimodal DBN model in an unsupervised manner. Tests on two available cancer datasets show that our integrative data analysis approach can effectively extract a unified representation of latent features to capture both intra- and cross-modality correlations, and identify meaningful disease subtypes from multi-platform cancer data. In addition, our approach can identify key genes and miRNAs that may play distinct roles in the pathogenesis of different cancer subtypes. Among those key miRNAs, we found that the expression level of miR-29a is highly correlated with survival time in ovarian cancer patients. These results indicate that our multimodal DBN based data analysis approach may have practical applications in cancer pathogenesis studies and provide useful guidelines for personalized cancer therapy.
Abstract-The minority-carrier mobility is an important parameter in the simulation of dc and frequency-dependent operation of bipolar devices. A self-consistent approach is proposed for extracting the minority-carrier mobility from fits to experimental data for lifetime and diffusion length and then comparing the extracted mobility to experimental mobility data. The good agreement between extracted and experimental mobilities justifies incorporating the results into numerical device and circuit CAD tools.
Background Patient portals are now widely available and increasingly adopted by patients and providers. Despite the growing research interest in patient portal adoption, there is a lack of follow-up studies describing the following: whether patients use portals actively; how frequently they use distinct portal functions; and, consequently, what the effects of using them are, the understanding of which is paramount to maximizing the potential of patient portals to enhance care delivery. Objective To investigate the characteristics of primary care patients using different patient portal functions and the impact of various portal usage behaviors on patients’ primary care service utilization and appointment adherence. Methods A retrospective, observational study using a large dataset of 46,544 primary care patients from University of Florida Health was conducted. Patient portal users were defined as patients who adopted a portal, and adoption was defined as the status that a portal account was opened and kept activated during the study period. Then, users were further classified into different user subgroups based on their portal usage of messaging, laboratory, appointment, and medication functions. The intervention outcomes were the rates of primary care office visits categorized as arrived, telephone encounters, cancellations, and no-shows per quarter as the measures of primary care service utilization and appointment adherence. Generalized linear models with a panel difference-in-differences study design were then developed to estimate the rate ratios between the users and the matched nonusers of the four measurements with an observational window of up to 10 quarters after portal adoption. Results Interestingly, a high propensity to adopt patient portals does not necessarily imply more frequent use of portals. In particular, the number of active health problems one had was significantly negatively associated with portal adoption (odds ratios [ORs] 0.57-0.86, 95% CIs 0.51-0.94, all P<.001) but was positively associated with portal usage (ORs 1.37-1.76, 95% CIs 1.11-2.22, all P≤.01). The same was true for being enrolled in Medicare for portal adoption (OR 0.47, 95% CI 0.41-0.54, P<.001) and message usage (OR 1.44, 95% CI 1.03-2.03, P=.04). On the impact of portal usage, the effects were time-dependent and specific to the user subgroup. The most salient change was the improvement in appointment adherence, and patients who used messaging and laboratory functions more often exhibited a larger reduction in no-shows compared to other user subgroups. Conclusions Patients differ in their portal adoption and usage behaviors, and the portal usage effects are heterogeneous and dynamic. However, there exists a lack of match in the patient portal market where patients who benefit the most from patient portals are not active portal adopters. Our findings suggest that health care delivery planners and administrators should remove the barriers of adoption for the portal beneficiaries; in addition, they should incorporate the impact of portal usage into care coordination and workflow design, ultimately aligning patients’ and providers’ needs and functionalities to effectively deliver patient-centric care.
Maintaining water balance is a universal challenge for organisms living in terrestrial environments, especially for insects, which have essential roles in our ecosystem. Although the high surface area to volume ratio in insects makes them vulnerable to water loss, insects have evolved different levels of desiccation resistance to adapt to diverse environments. To withstand desiccation, insects use a lipid layer called cuticular hydrocarbons (CHCs) to reduce water evaporation from the body surface. It has long been hypothesized that the waterproofing capability of this CHC layer, which can confer different levels of desiccation resistance, depends on its chemical composition. However, it is unknown which CHC components are important contributors to desiccation resistance and how these components can determine differences in desiccation resistance. In this study, we used machine learning algorithms, correlation analyses, and synthetic CHCs to investigate how different CHC components affect desiccation resistance in 50 Drosophila and related species. We showed that desiccation resistance differences across these species can be largely explained by variation in CHC composition. In particular, length variation in a subset of CHCs, the methyl-branched CHCs (mbCHCs), is a key determinant of desiccation resistance. There is also a significant correlation between the evolution of longer mbCHCs and higher desiccation resistance in these species. Given that CHCs are almost ubiquitous in insects, we suggest that evolutionary changes in insect CHC components can be a general mechanism for the evolution of desiccation resistance and adaptation to diverse and changing environments.
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