2,021 research outputs found

    Computational Models for Transplant Biomarker Discovery.

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    Translational medicine offers a rich promise for improved diagnostics and drug discovery for biomedical research in the field of transplantation, where continued unmet diagnostic and therapeutic needs persist. Current advent of genomics and proteomics profiling called "omics" provides new resources to develop novel biomarkers for clinical routine. Establishing such a marker system heavily depends on appropriate applications of computational algorithms and software, which are basically based on mathematical theories and models. Understanding these theories would help to apply appropriate algorithms to ensure biomarker systems successful. Here, we review the key advances in theories and mathematical models relevant to transplant biomarker developments. Advantages and limitations inherent inside these models are discussed. The principles of key -computational approaches for selecting efficiently the best subset of biomarkers from high--dimensional omics data are highlighted. Prediction models are also introduced, and the integration of multi-microarray data is also discussed. Appreciating these key advances would help to accelerate the development of clinically reliable biomarker systems

    Hemodynamic Deconvolution Demystified: Sparsity-Driven Regularization at Work

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    Deconvolution of the hemodynamic response is an important step to access short timescales of brain activity recorded by functional magnetic resonance imaging (fMRI). Albeit conventional deconvolution algorithms have been around for a long time (e.g., Wiener deconvolution), recent state-of-the-art methods based on sparsity-pursuing regularization are attracting increasing interest to investigate brain dynamics and connectivity with fMRI. This technical note revisits the main concepts underlying two main methods, Paradigm Free Mapping and Total Activation, in the most accessible way. Despite their apparent differences in the formulation, these methods are theoretically equivalent as they represent the synthesis and analysis sides of the same problem, respectively. We demonstrate this equivalence in practice with their best-available implementations using both simulations, with different signal-to-noise ratios, and experimental fMRI data acquired during a motor task and resting-state. We evaluate the parameter settings that lead to equivalent results, and showcase the potential of these algorithms compared to other common approaches. This note is useful for practitioners interested in gaining a better understanding of state-of-the-art hemodynamic deconvolution, and aims to answer questions that practitioners often have regarding the differences between the two methods.Comment: 18 pages, 6 figures, submitted to Apertur

    Information Transfer in Linear Multivariate Processes Assessed through Penalized Regression Techniques: Validation and Application to Physiological Networks

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    The framework of information dynamics allows the dissection of the information processed in a network of multiple interacting dynamical systems into meaningful elements of computation that quantify the information generated in a target system, stored in it, transferred to it from one or more source systems, and modified in a synergistic or redundant way. The concepts of information transfer and modification have been recently formulated in the context of linear parametric modeling of vector stochastic processes, linking them to the notion of Granger causality and providing efficient tools for their computation based on the state–space (SS) representation of vector autoregressive (VAR) models. Despite their high computational reliability these tools still suffer from estimation problems which emerge, in the case of low ratio between data points available and the number of time series, when VAR identification is performed via the standard ordinary least squares (OLS). In this work we propose to replace the OLS with penalized regression performed through the Least Absolute Shrinkage and Selection Operator (LASSO), prior to computation of the measures of information transfer and information modification. First, simulating networks of several coupled Gaussian systems with complex interactions, we show that the LASSO regression allows, also in conditions of data paucity, to accurately reconstruct both the underlying network topology and the expected patterns of information transfer. Then we apply the proposed VAR-SS-LASSO approach to a challenging application context, i.e., the study of the physiological network of brain and peripheral interactions probed in humans under different conditions of rest and mental stress. Our results, which document the possibility to extract physiologically plausible patterns of interaction between the cardiovascular, respiratory and brain wave amplitudes, open the way to the use of our new analysis tools to explore the emerging field of Network Physiology in several practical applications
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