MiSurv: an Integrative Web Cloud Platform for User-Friendly Microbiome Data Analysis with Survival Responses.

Investigators have studied the treatment effects on human health or disease, the treatment effects on human microbiome, and the roles of the microbiome on human health or disease. Especially, in a clinical trial, investigators commonly trace disease status over a lengthy period to survey the sequential disease progression for different treatment groups (e.g., treatment versus placebo, new treatment versus old treatment). Hence, disease responses are often available in the form of survival (i.e., time-to-event) responses stratified by treatment groups. While the recent web cloud platforms have enabled user-friendly microbiome data processing and analytics, there is currently no web cloud platform to analyze microbiome data with survival responses. Therefore, we introduce here an integrative web cloud platform, called MiSurv, for comprehensive microbiome data analysis with survival responses. IMPORTANCE MiSurv consists of a data processing module and its following four data analytic modules: (i) Module 1: Comparative survival analysis between treatment groups, (ii) Module 2: Comparative analysis in microbial composition between treatment groups, (iii) Module 3: Association testing between microbial composition and survival responses, (iv) Module 4: Prediction modeling using microbial taxa on survival responses. We demonstrate its use through an example trial on the effects of antibiotic use on the survival rate against type 1 diabetes (T1D) onset and gut microbiome composition, respectively, and the effects of the gut microbiome on the survival rate against T1D onset. MiSurv is freely available on our web server (http://misurv.micloud.kr) or can alternatively run on the user's local computer (https://github.com/wg99526/MiSurvGit).

Integrative web cloud computing and analytics using MiPair for design-based comparative analysis with paired microbiome data.

Pairing (or blocking) is a design technique that is widely used in comparative microbiome studies to efficiently control for the effects of potential confounders (e.g., genetic, environmental, or behavioral factors). Some typical paired (block) designs for human microbiome studies are repeated measures designs that profile each subject's microbiome twice (or more than twice) (1) for pre and post treatments to see the effects of a treatment on microbiome, or (2) for different organs of the body (e.g., gut, mouth, skin) to see the disparity in microbiome between (or across) body sites. Researchers have developed a sheer number of web-based tools for user-friendly microbiome data processing and analytics, though there is no web-based tool currently available for such paired microbiome studies. In this paper, we thus introduce an integrative web-based tool, named MiPair, for design-based comparative analysis with paired microbiome data. MiPair is a user-friendly web cloud service that is built with step-by-step data processing and analytic procedures for comparative analysis between (or across) groups or between baseline and other groups. MiPair employs parametric and non-parametric tests for complete or incomplete block designs to perform comparative analyses with respect to microbial ecology (alpha- and beta-diversity) and taxonomy (e.g., phylum, class, order, family, genus, species). We demonstrate its usage through an example clinical trial on the effects of antibiotics on gut microbiome. MiPair is an open-source software that can be run on our web server ( http://mipair.micloud.kr ) or on user's computer ( https://github.com/yj7599/mipairgit ).

MiCloud: A unified web platform for comprehensive microbiome data analysis.

The recent advance in massively parallel sequencing has enabled accurate microbiome profiling at a dramatically lowered cost. Then, the human microbiome has been the subject of intensive investigation in public health and medicine. In the meanwhile, researchers have developed lots of microbiome data analysis methods, protocols, and/or tools. Among those, especially, the web platforms can be highlighted because of the user-friendly interfaces and streamlined protocols for a long sequence of analytic procedures. However, existing web platforms can handle only a categorical trait of interest, cross-sectional study design, and the analysis with no covariate adjustment. We therefore introduce here a unified web platform, named MiCloud, for a binary or continuous trait of interest, cross-sectional or longitudinal/family-based study design, and with or without covariate adjustment. MiCloud handles all such types of analyses for both ecological measures (i.e., alpha and beta diversity indices) and microbial taxa in relative abundance on different taxonomic levels (i.e., phylum, class, order, family, genus and species). Importantly, MiCloud also provides a unified analytic protocol that streamlines data inputs, quality controls, data transformations, statistical methods and visualizations with vastly extended utility and flexibility that are suited to microbiome data analysis. We illustrate the use of MiCloud through the United Kingdom twin study on the association between gut microbiome and body mass index adjusting for age. MiCloud can be implemented on either the web server (http://micloud.kr) or the user's computer (https://github.com/wg99526/micloudgit).

Deep-learning-based automated terminology mapping in OMOP-CDM.

OBJECTIVE: Accessing medical data from multiple institutions is difficult owing to the interinstitutional diversity of vocabularies. Standardization schemes, such as the common data model, have been proposed as solutions to this problem, but such schemes require expensive human supervision. This study aims to construct a trainable system that can automate the process of semantic interinstitutional code mapping. MATERIALS AND METHODS: To automate mapping between source and target codes, we compute the embedding-based semantic similarity between corresponding descriptive sentences. We also implement a systematic approach for preparing training data for similarity computation. Experimental results are compared to traditional word-based mappings. RESULTS: The proposed model is compared against the state-of-the-art automated matching system, which is called Usagi, of the Observational Medical Outcomes Partnership common data model. By incorporating multiple negative training samples per positive sample, our semantic matching method significantly outperforms Usagi. Its matching accuracy is at least 10% greater than that of Usagi, and this trend is consistent across various top-k measurements. DISCUSSION: The proposed deep learning-based mapping approach outperforms previous simple word-level matching algorithms because it can account for contextual and semantic information. Additionally, we demonstrate that the manner in which negative training samples are selected significantly affects the overall performance of the system. CONCLUSION: Incorporating the semantics of code descriptions more significantly increases matching accuracy compared to traditional text co-occurrence-based approaches. The negative training sample collection methodology is also an important component of the proposed trainable system that can be adopted in both present and future related systems.

MildInt: Deep Learning-Based Multimodal Longitudinal Data Integration Framework.

As large amounts of heterogeneous biomedical data become available, numerous methods for integrating such datasets have been developed to extract complementary knowledge from multiple domains of sources. Recently, a deep learning approach has shown promising results in a variety of research areas. However, applying the deep learning approach requires expertise for constructing a deep architecture that can take multimodal longitudinal data. Thus, in this paper, a deep learning-based python package for data integration is developed. The python package deep learning-based multimodal longitudinal data integration framework (MildInt) provides the preconstructed deep learning architecture for a classification task. MildInt contains two learning phases: learning feature representation from each modality of data and training a classifier for the final decision. Adopting deep architecture in the first phase leads to learning more task-relevant feature representation than a linear model. In the second phase, linear regression classifier is used for detecting and investigating biomarkers from multimodal data. Thus, by combining the linear model and the deep learning model, higher accuracy and better interpretability can be achieved. We validated the performance of our package using simulation data and real data. For the real data, as a pilot study, we used clinical and multimodal neuroimaging datasets in Alzheimer's disease to predict the disease progression. MildInt is capable of integrating multiple forms of numerical data including time series and non-time series data for extracting complementary features from the multimodal dataset.

Predicting Alzheimer's disease progression using multi-modal deep learning approach.

Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by a decline in cognitive functions with no validated disease modifying treatment. It is critical for timely treatment to detect AD in its earlier stage before clinical manifestation. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal older adults and AD. To predict conversion from MCI to probable AD, we applied a deep learning approach, multimodal recurrent neural network. We developed an integrative framework that combines not only cross-sectional neuroimaging biomarkers at baseline but also longitudinal cerebrospinal fluid (CSF) and cognitive performance biomarkers obtained from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI). The proposed framework integrated longitudinal multi-domain data. Our results showed that 1) our prediction model for MCI conversion to AD yielded up to 75% accuracy (area under the curve (AUC) = 0.83) when using only single modality of data separately; and 2) our prediction model achieved the best performance with 81% accuracy (AUC = 0.86) when incorporating longitudinal multi-domain data. A multi-modal deep learning approach has potential to identify persons at risk of developing AD who might benefit most from a clinical trial or as a stratification approach within clinical trials.

Biological Brain Age Prediction Using Cortical Thickness Data: A Large Scale Cohort Study.

Brain age estimation from anatomical features has been attracting more attention in recent years. This interest in brain age estimation is motivated by the importance of biological age prediction in health informatics, with an application to early prediction of neurocognitive disorders. It is well-known that normal brain aging follows a specific pattern, which enables researchers and practitioners to predict the age of a human's brain from its degeneration. In this paper, we model brain age predicted by cortical thickness data gathered from large cohort brain images. We collected 2,911 cognitively normal subjects (age 45-91 years) at a single medical center and acquired their brain magnetic resonance (MR) images. All images were acquired using the same scanner with the same protocol. We propose to first apply Sparse Group Lasso (SGL) for feature selection by utilizing the brain's anatomical grouping. Once the features are selected, a non-parametric non-linear regression using the Gaussian Process Regression (GPR) algorithm is applied to fit the final age prediction model. Experimental results demonstrate that the proposed method achieves the mean absolute error of 4.05 years, which is comparable with or superior to several recent methods. Our method can also be a critical tool for clinicians to differentiate patients with neurodegenerative brain disease by extracting a cortical thinning pattern associated with normal aging.