191 research outputs found

    Outcome prediction based on microarray analysis: a critical perspective on methods

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    <p>Abstract</p> <p>Background</p> <p>Information extraction from microarrays has not yet been widely used in diagnostic or prognostic decision-support systems, due to the diversity of results produced by the available techniques, their instability on different data sets and the inability to relate statistical significance with biological relevance. Thus, there is an urgent need to address the statistical framework of microarray analysis and identify its drawbacks and limitations, which will enable us to thoroughly compare methodologies under the same experimental set-up and associate results with confidence intervals meaningful to clinicians. In this study we consider gene-selection algorithms with the aim to reveal inefficiencies in performance evaluation and address aspects that can reduce uncertainty in algorithmic validation.</p> <p>Results</p> <p>A computational study is performed related to the performance of several gene selection methodologies on publicly available microarray data. Three basic types of experimental scenarios are evaluated, i.e. the independent test-set and the 10-fold cross-validation (CV) using maximum and average performance measures. Feature selection methods behave differently under different validation strategies. The performance results from CV do not mach well those from the independent test-set, except for the support vector machines (SVM) and the least squares SVM methods. However, these wrapper methods achieve variable (often low) performance, whereas the hybrid methods attain consistently higher accuracies. The use of an independent test-set within CV is important for the evaluation of the predictive power of algorithms. The optimal size of the selected gene-set also appears to be dependent on the evaluation scheme. The consistency of selected genes over variation of the training-set is another aspect important in reducing uncertainty in the evaluation of the derived gene signature. In all cases the presence of outlier samples can seriously affect algorithmic performance.</p> <p>Conclusion</p> <p>Multiple parameters can influence the selection of a gene-signature and its predictive power, thus possible biases in validation methods must always be accounted for. This paper illustrates that independent test-set evaluation reduces the bias of CV, and case-specific measures reveal stability characteristics of the gene-signature over changes of the training set. Moreover, frequency measures on gene selection address the algorithmic consistency in selecting the same gene signature under different training conditions. These issues contribute to the development of an objective evaluation framework and aid the derivation of statistically consistent gene signatures that could eventually be correlated with biological relevance. The benefits of the proposed framework are supported by the evaluation results and methodological comparisons performed for several gene-selection algorithms on three publicly available datasets.</p

    Reconfiguration of dominant coupling modes in mild traumatic brain injury mediated by δ-band activity: a resting state MEG study

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    During the last few years, rich-club (RC) organization has been studied as a possible brain-connectivity organization model for large-scale brain networks. At the same time, empirical and simulated data of neurophysiological models have demonstrated the significant role of intra-frequency and inter-frequency coupling among distinct brain areas. The current study investigates further the importance of these couplings using recordings of resting-state magnetoencephalographic activity obtained from 30 mild traumatic brain injury (mTBI) subjects and 50 healthy controls. Intra-frequency and inter-frequency coupling modes are incorporated in a single graph to detect group differences within individual rich-club subnetworks (type I networks) and networks connecting RC nodes with the rest of the nodes (type II networks). Our results show a higher probability of inter-frequency coupling for (δ–γ1), (δ–γ2), (θ–β), (θ–γ2), (α–γ2), (γ1–γ2) and intra-frequency coupling for (γ1–γ1) and (δ–δ) for both type I and type II networks in the mTBI group. Additionally, mTBI and control subjects can be correctly classified with high accuracy (98.6%), whereas a general linear regression model can effectively predict the subject group using the ratio of type I and type II coupling in the (δ, θ), (δ, β), (δ, γ1), and (δ, γ2) frequency pairs. These findings support the presence of an RC organization simultaneously with dominant frequency interactions within a single functional graph. Our results demonstrate a hyperactivation of intrinsic RC networks in mTBI subjects compared to controls, which can be seen as a plausible compensatory mechanism for alternative frequency-dependent routes of information flow in mTBI subjects

    Improving the detection of mtbi via complexity analysis in resting - state magnetoencephalography

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    Diagnosis of mild Traumatic Brain Injury (mTBI) is difficult due to the variability of obvious brain lesions using imaging scans. A promising tool for exploring potential biomarkers for mTBI is magnetoencephalography which has the advantage of high spatial and temporal resolution. By adopting proper analytic tools from the field of symbolic dynamics like Lempel-Ziv complexity, we can objectively characterize neural network alterations compared to healthy control by enumerating the different patterns of a symbolic sequence. This procedure oversimplifies the rich information of brain activity captured via MEG. For that reason, we adopted neural-gas algorithm which can transform a time series into more than two symbols by learning brain dynamics with a small reconstructed error. The proposed analysis was applied to recordings of 30 mTBI patients and 50 normal controls in δ frequency band. Our results demonstrated that mTBI patients could be separated from normal controls with more than 97% classification accuracy based on high complexity regions corresponding to right frontal areas. In addition, a reverse relation between complexity and transition rate was demonstrated for both groups. These findings indicate that symbolic complexity could have a significant predictive value in the development of reliable biomarkers to help with the early detection of mTBI

    Functional connectivity analysis of cerebellum using spatially constrained spectral clustering

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    The human cerebellum contains almost 50% of the neurons in the brain, although its volume does not exceed 10% of the total brain volume. The goal of this study is to derive the functional network of the cerebellum during the resting-state and then compare the ensuing group networks between males and females. Toward this direction, a spatially constrained version of the classic spectral clustering algorithm is proposed and then compared against conventional spectral graph theory approaches, such as spectral clustering, and N-cut, on synthetic data as well as on resting-state fMRI data obtained from the Human Connectome Project (HCP). The extracted atlas was combined with the anatomical atlas of the cerebellum resulting in a functional atlas with 46 regions of interest. As a final step, a gender-based network analysis of the cerebellum was performed using the data-driven atlas along with the concept of the minimum spanning trees. The simulation analysis results confirm the dominance of the spatially constrained spectral clustering approach in discriminating activation patterns under noisy conditions. The network analysis results reveal statistically significant differences in the optimal tree organization between males and females. In addition, the dominance of the left VI lobule in both genders supports the results reported in a previous study of ours. To our knowledge, the extracted atlas comprises the first resting-state atlas of the cerebellum based on HCP data

    FCLAB:An EEGLAB module for performing functional connectivity analysis on single-subject EEG data

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    Functional connectivity (FC) analysis constitutes a fundamental neuroscientific approach that has been extensively used for the investigation of brain's connectivity and activation patterns. To that end, several software tools have been developed. This paper presents FCLAB, the only EEGLAB-based plugin, which is able to work with EEG signals in order to estimate and visualize brain functional connectivity networks based on a variety of similarity measures as well as run a complete graph analysis procedure followed by a detailed visualization of the ensuing local and global measures distribution. FCLAB entails optimization procedures for the implementation of the connectivity structures and is the result of long-term research in EEG functional connectivity. The computed functional connectivity measures have been carefully selected to reflect the state-of-art in the field. Future work focuses on extending the platform for multi-subject analysis in order to enable the implementation of statistical analysis tools

    Parametric and Nonparametric EEG Analysis for the Evaluation of EEG Activity in Young Children with Controlled Epilepsy

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    There is an important evidence of differences in the EEG frequency spectrum of control subjects as compared to epileptic subjects. In particular, the study of children presents difficulties due to the early stages of brain development and the various forms of epilepsy indications. In this study, we consider children that developed epileptic crises in the past but without any other clinical, psychological, or visible neurophysiological findings. The aim of the paper is to develop reliable techniques for testing if such controlled epilepsy induces related spectral differences in the EEG. Spectral features extracted by using nonparametric, signal representation techniques (Fourier and wavelet transform) and a parametric, signal modeling technique (ARMA) are compared and their effect on the classification of the two groups is analyzed. The subjects performed two different tasks: a control (rest) task and a relatively difficult math task. The results show that spectral features extracted by modeling the EEG signals recorded from individual channels by an ARMA model give a higher discrimination between the two subject groups for the control task, where classification scores of up to 100% were obtained with a linear discriminant classifier

    Review on solving the inverse problem in EEG source analysis

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    In this primer, we give a review of the inverse problem for EEG source localization. This is intended for the researchers new in the field to get insight in the state-of-the-art techniques used to find approximate solutions of the brain sources giving rise to a scalp potential recording. Furthermore, a review of the performance results of the different techniques is provided to compare these different inverse solutions. The authors also include the results of a Monte-Carlo analysis which they performed to compare four non parametric algorithms and hence contribute to what is presently recorded in the literature. An extensive list of references to the work of other researchers is also provided
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