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Convolutional Neural Networks (CNN) are often unsuitable for predictive modeling involving nonimage based biological features. Here, the authors present a mapping termed REFINED to represent high dimensional vectors as compact images with spatial correlation that makes it compatible with CNN based learning.

Abstract Background Clinical studies often track dose-response curves of subjects over time. One can easily model the dose-response curve at each time point with Hill equation, but such a model fails to capture the temporal evolution of the curves. On the other hand, one can use Gompertz equation to model the temporal behaviors at each dose without capturing the evolution of time curves across dosage. Results In this article, we propose a parametric model for dose-time responses that follows Gompertz law in time and Hill equation across dose approximately. We derive a recursion relation for dose-response curves over time capturing the temporal evolution and then specify a regression model connecting the parameters controlling the dose-time responses with individual level proteomic data. The resultant joint model allows us to predict the dose-response curves over time for new individuals. Conclusion We have compared the efficacy of our proposed Recursive Hybrid model with individual dose-response predictive models at desired time points. We note that our proposed model exhibits a superior performance compared to the individual ones for both synthetic data and actual pharmacological data. For the desired dose-time varying genetic characterization and drug response values, we have used the HMS-LINCS database and demonstrated the effectiveness of our model for all available anticancer compounds.

Abstract Background In precision medicine, scarcity of suitable biological data often hinders the design of an appropriate predictive model. In this regard, large scale pharmacogenomics studies, like CCLE and GDSC hold the promise to mitigate the issue. However, one cannot directly employ data from multiple sources together due to the existing distribution shift in data. One way to solve this problem is to utilize the transfer learning methodologies tailored to fit in this specific context. Results In this paper, we present two novel approaches for incorporating information from a secondary database for improving the prediction in a target database. The first approach is based on latent variable cost optimization and the second approach considers polynomial mapping between the two databases. Utilizing CCLE and GDSC databases, we illustrate that the proposed approaches accomplish a better prediction of drug sensitivities for different scenarios as compared to the existing approaches. Conclusion We have compared the performance of the proposed predictive models with database-specific individual models as well as existing transfer learning approaches. We note that our proposed approaches exhibit superior performance compared to the abovementioned alternative techniques for predicting sensitivity for different anti-cancer compounds, particularly the nonlinear mapping model shows the best overall performance.

Abstract Background A significant problem in precision medicine is the prediction of drug sensitivity for individual cancer cell lines. Predictive models such as Random Forests have shown promising performance while predicting from individual genomic features such as gene expressions. However, accessibility of various other forms of data types including information on multiple tested drugs necessitates the examination of designing predictive models incorporating the various data types. Results We explore the predictive performance of model stacking and the effect of stacking on the predictive bias and squared error. In addition we discuss the analytical underpinnings supporting the advantages of stacking in reducing squared error and inherent bias of random forests in prediction of outliers. The framework is tested on a setup including gene expression, drug target, physical properties and drug response information for a set of drugs and cell lines. Conclusion The performance of individual and stacked models are compared. We note that stacking models built on two heterogeneous datasets provide superior performance to stacking different models built on the same dataset. It is also noted that stacking provides a noticeable reduction in the bias of our predictors when the dominant eigenvalue of the principle axis of variation in the residuals is significantly higher than the remaining eigenvalues.

Modeling sensitivity to drugs based on genetic characterizations is a significant challenge in the area of systems medicine. Ensemble based approaches such as Random Forests have been shown to perform well in both individual sensitivity prediction studies and team science based prediction challenges. However, Random Forests generate a deterministic predictive model for each drug based on the genetic characterization of the cell lines and ignores the relationship between different drug sensitivities during model generation. This application motivates the need for generation of multivariate ensemble learning techniques that can increase prediction accuracy and improve variable importance ranking by incorporating the relationships between different output responses. In this article, we propose a novel cost criterion that captures the dissimilarity in the output response structure between the training data and node samples as the difference in the two empirical copulas. We illustrate that copulas are suitable for capturing the multivariate structure of output responses independent of the marginal distributions and the copula based multivariate random forest framework can provide higher accuracy prediction and improved variable selection. The proposed framework has been validated on genomics of drug sensitivity for cancer and cancer cell line encyclopedia database.

Random forests consisting of an ensemble of regression trees with equal weights are frequently used for design of predictive models. In this article, we consider an extension of the methodology by representing the regression trees in the form of probabilistic trees and analyzing the nature of heteroscedasticity. The probabilistic tree representation allows for analytical computation of confidence intervals (CIs), and the tree weight optimization is expected to provide stricter CIs with comparable performance in mean error. We approached the ensemble of probabilistic trees’ prediction from the perspectives of a mixture distribution and as a weighted sum of correlated random variables. We applied our methodology to the drug sensitivity prediction problem on synthetic and cancer cell line encyclopedia dataset and illustrated that tree weights can be selected to reduce the average length of the CI without increase in mean error.

Precision medicine entails the design of therapies that are matched for each individual patient. Thus, predictive modeling of drug responses for specific patients constitutes a significant challenge for personalized therapy. In this article, we consider a review of approaches that have been proposed to tackle the drug sensitivity prediction problem especially with respect to personalized cancer therapy. We first discuss modeling approaches that are based on genomic characterizations alone and further the discussion by including modeling techniques that integrate both genomic and functional information. A comparative analysis of the prediction performance of four representative algorithms, elastic net, random forest, kernelized Bayesian multi-task learning and deep learning, reflecting the broad classes of regularized linear, ensemble, kernelized and neural network-based models, respectively, has been included in the paper. The review also considers the challenges that need to be addressed for successful implementation of the algorithms in clinical practice.

A total of 209 species were documented where 181 species were used against 379 diseases/ailments from a village common forest of Rangamati, Bangladesh. Leaves were reported as most utilized plant part while herbs were dominant. Diversity indices revealed that the study area was rich in diverse medicinal plants. Collected voucher specimens were deposited in the Chittagong university Herbarium with an accession number. [ABSTRACT FROM AUTHOR]

Abstract Background Daqu, the saccharification, fermentation, and aroma-producing agents for Baijiu brewing, is prepared using a complex process. Aging is important for improving the quality of Daqu, but its impact has rarely been studied. This study investigated changes in the physicochemical properties, flavor compounds, and microbial communities during aging of Daqu with a roasted sesame-like flavor. Results The physicochemical properties changed continuously during aging to provide a high esterifying activity. Aging removed unpleasant flavor compounds and helped to stabilize the flavor compounds in mature Daqu. A high-throughput sequencing approach was used to analyze the changing composition of the microbial communities during aging. Aging helped to modify the microbial population to produce better Baijiu by eliminating low-abundance microbial communities and optimizing the proportion of predominant microbial communities. Nine genera of prokaryotic microbes formed the core microbiota in Daqu after aging. Regarding eukaryotic microbes, Zygomycota, the predominant community, increased in the first 2 months, then decreased in the third month of aging, while Ascomycota, the subdominant community, showed the opposite behavior. Absidia, Trichocomaceae_norank and Rhizopus were the predominant genera in the mature Daqu. Conclusions Significant correlations between microbiota and physicochemical properties or flavor compounds were observed, indicating that optimizing microbial communities is essential for aging Daqu. This study provides detailed information on aging during Daqu preparation.

A middle aged woman presenting with fatigue, pruritus, xanthelesma and hepatomegaly remains the typical presentation of primary biliary cirrhosis. Here, we present a case of primary biliary cirrhosis occurring in a male patient, who presented with fatigue and pruritus, had hepato-splenomegaly, raised serum alkaline phosphatase, positive anti-mitrochondrial antibody and negative antinuclear antibody. [ABSTRACT FROM AUTHOR]