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Robust probabilistic classification applicable to irregularly sampled functional data.

ABSTRACT: A robust probabilistic classifier for functional data is developed to predict class membership based on functional input measurements and to provide a reliable probability estimates for class membership. The method combines a Bayes classifier and semi-parametric mixed effects model with robust tuning parameter to make the method robust to outlying curves, and to improve the accuracy of the risk or uncertainty estimates, which is crucial in medical diagnostic applications. The approach applies to functional data with varying ranges and irregular sampling without making parametric assumptions on the within-curve covariance. Simulation studies evaluate the proposed method and competitors in terms of sensitivity to heavy tailed functional distributions and outlying curves. Classification performance is evaluated by both error rate and logloss, the latter of which imposes heavier penalties on highly confident errors than on less confident errors. Runtime experiments on the R implementation indicate that the proposed method scales well computationally. Illustrative applications include data from quantitative ultrasound analysis and phoneme recognition.

SUBMITTER: Park Y

PROVIDER: S-EPMC6510497 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Robust probabilistic classification applicable to irregularly sampled functional data.

Park Yeonjoo Y Simpson Douglas G DG

Computational statistics & data analysis 20180811

A robust probabilistic classifier for functional data is developed to predict class membership based on functional input measurements and to provide a reliable probability estimates for class membership. The method combines a Bayes classifier and semi-parametric mixed effects model with robust tuning parameter to make the method robust to outlying curves, and to improve the accuracy of the risk or uncertainty estimates, which is crucial in medical diagnostic applications. The approach applies to ...[more]

PMID: 31086427

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Project description:MotivationIdentification of system-wide causal relationships can contribute to our understanding of long-distance, intercellular signaling in biological organisms. Dynamic transcriptome analysis holds great potential to uncover coordinated biological processes between organs. However, many existing dynamic transcriptome studies are characterized by sparse and often unevenly spaced time points that make the identification of causal relationships across organs analytically challenging. Application of existing statistical models, designed for regular time series with abundant time points, to sparse data may fail to reveal biologically significant, causal relationships. With increasing research interest in biological time series data, there is a need for new statistical methods that are able to determine causality within and between time series data sets. Here, a statistical framework was developed to identify (Granger) causal gene-gene relationships of unevenly spaced, multivariate time series data from two different tissues of Arabidopsis thaliana in response to a nitrogen signal.ResultsThis work delivers a statistical approach for modelling irregularly sampled bivariate signals which embeds functions from the domain of engineering that allow to adapt the model's dependence structure to the specific sampling time. Using Maximum-Likelihood to estimate the parameters of this model for each bivariate time series, it is then possible to use bootstrap procedures for small samples (or asymptotics for large samples) in order to test for Granger-Causality. When applied to the Arabidopsis thaliana data, the proposed approach produced 3,078 significant interactions, in which 2,012 interactions have root causal genes and 1,066 interactions have shoot causal genes. Many of the predicted causal and target genes are known players in local and long-distance nitrogen signaling, including genes encoding transcription factors, hormones, and signaling peptides. Of the 1,007 total causal genes (either organ), 384 are either known or predicted mobile transcripts, suggesting that the identified causal genes may be directly involved in long-distance nitrogen signaling through intercellular interactions. The model predictions and subsequent network analysis identified nitrogen-responsive genes that can be further tested for their specific roles in long-distance nitrogen signaling.AvailabilityThe method was developed with the R statistical software and is made available through the R package "irg" hosted on the GitHub repository https://github.com/SMAC-Group/irg where also a running example vignette can be found (https://smac-group.github.io/irg/articles/vignette.html). A few signals from the original data set are made available in the package as an example to apply the method and the complete Arabidopsis thaliana data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE97500.Supplementary informationSupplementary data are available at Bioinformatics online.

Project description:Development of robust and efficient methods for analyzing and interpreting high dimension gene expression profiles continues to be a focus in computational biology. The accumulated experiment evidence supports the assumption that genes express and perform their functions in modular fashions in cells. Therefore, there is an open space for development of the timely and relevant computational algorithms that use robust functional expression profiles towards precise classification of complex human diseases at the modular level.Inspired by the insight that genes act as a module to carry out a highly integrated cellular function, we thus define a low dimension functional expression profile for data reduction. After annotating each individual gene to functional categories defined in a proper gene function classification system such as Gene Ontology applied in this study, we identify those functional categories enriched with differentially expressed genes. For each functional category or functional module, we compute a summary measure (s) for the raw expression values of the annotated genes to capture the overall activity level of the module. In this way, we can treat the gene expressions within a functional module as an integrative data point to replace the multiple values of individual genes. We compare the classification performance of decision trees based on functional expression profiles with the conventional gene expression profiles using four publicly available datasets, which indicates that precise classification of tumour types and improved interpretation can be achieved with the reduced functional expression profiles.This modular approach is demonstrated to be a powerful alternative approach to analyzing high dimension microarray data and is robust to high measurement noise and intrinsic biological variance inherent in microarray data. Furthermore, efficient integration with current biological knowledge has facilitated the interpretation of the underlying molecular mechanisms for complex human diseases at the modular level.

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Robust probabilistic classification applicable to irregularly sampled functional data.

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Robust probabilistic classification applicable to irregularly sampled functional data.

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