Functional Connectivity Analysis of Mental Fatigue Reveals Different Network Topological Alterations Between Driving and Vigilance Tasks.

Despite the apparent importance of mental fatigue detection, a reliable application is hindered due to the incomprehensive understanding of the neural mechanisms of mental fatigue. In this paper, we investigated the topological alterations of functional brain networks in the theta band (4 - 7 Hz) of electroencephalography (EEG) data from 40 male subjects undergoing two distinct fatigue-inducing tasks: a low-intensity one-hour simulated driving and a high-demanding half-hour sustained attention task [psychomotor vigilance task (PVT)]. Behaviorally, subjects demonstrated a robust mental fatigue effect, as reflected by significantly declined performances in cognitive tasks prior and post these two tasks. Furthermore, characteristic path length presented a positive correlation with task duration, which led to a significant increase between the first and the last five minutes of both tasks, indicating a fatigue-related disruption in information processing efficiency. However, significantly increased clustering coefficient was revealed only in the driving task, suggesting distinct network reorganizations between the two fatigue-inducing tasks. Moreover, high accuracy (92% for driving; 97% for PVT) was achieved for fatigue classification with apparently different discriminative functional connectivity features. These findings augment our understanding of the complex nature of fatigue-related neural mechanisms and demonstrate the feasibility of using functional connectivity as neural biomarkers for applicable fatigue monitoring.

Self-Trained LMT for Semisupervised Learning.

The most important asset of semisupervised classification methods is the use of available unlabeled data combined with a clearly smaller set of labeled examples, so as to increase the classification accuracy compared with the default procedure of supervised methods, which on the other hand use only the labeled data during the training phase. Both the absence of automated mechanisms that produce labeled data and the high cost of needed human effort for completing the procedure of labelization in several scientific domains rise the need for semisupervised methods which counterbalance this phenomenon. In this work, a self-trained Logistic Model Trees (LMT) algorithm is presented, which combines the characteristics of Logistic Trees under the scenario of poor available labeled data. We performed an in depth comparison with other well-known semisupervised classification methods on standard benchmark datasets and we finally reached to the point that the presented technique had better accuracy in most cases.

Identifying disease network perturbations through regression on gene expression and pathway topology analysis.

In Systems Biology, network-based approaches have been extensively used to effectively study complex diseases. An important challenge is the detection of network perturbations which disrupt regular biological functions as a result of a disease. In this regard, we introduce a network based pathway analysis method which isolates casual interactions with significant regulatory roles within diseased-perturbed pathways. Specifically, we use gene expression data with Random Forest regression models to assess the interactivity strengths of genes within disease-perturbed networks, using KEGG pathway maps as a source of prior-knowledge pertaining to pathway topology. We deliver as output a network with imprinted perturbations corresponding to the biological phenomena arising in a disease-oriented experiment. The efficacy of our approach is demonstrated on a serous papillary ovarian cancer experiment and results highlight the functional roles of high impact interactions and key gene regulators which cause strong perturbations on pathway networks, in accordance with experimentally validated knowledge from recent literature.

Joint spatial-spectral feature space clustering for speech activity detection from ECoG signals.

Brain-machine interfaces for speech restoration have been extensively studied for more than two decades. The success of such a system will depend in part on selecting the best brain recording sites and signal features corresponding to speech production. The purpose of this study was to detect speech activity automatically from electrocorticographic signals based on joint spatial-frequency clustering of the ECoG feature space. For this study, the ECoG signals were recorded while a subject performed two different syllable repetition tasks. We found that the optimal frequency resolution to detect speech activity from ECoG signals was 8 Hz, achieving 98.8% accuracy by employing support vector machines as a classifier. We also defined the cortical areas that held the most information about the discrimination of speech and nonspeech time intervals. Additionally, the results shed light on the distinct cortical areas associated with the two syllables repetition tasks and may contribute to the development of portable ECoG-based communication.

Influenza A immunomics and public health omics: the dynamic pathway interplay in host response to H1N1 infection.

Towards unraveling the influenza A (H1N1) immunome, this work aims at constructing the murine host response pathway interactome. To accomplish that, an ensemble of dynamic and time-varying Gene Regulatory Network Inference methodologies was recruited to set a confident interactome based on mouse time series transcriptome data (day 1-day 60). The proposed H1N1 interactome demonstrated significant transformations among activated and suppressed pathways in time. Enhanced interplay was observed at day 1, while the maximal network complexity was reached at day 8 (correlated with viral clearance and iBALT tissue formation) and one interaction was present at day 40. Next, we searched for common interactivity features between the murine-adapted PR8 strain and other influenza A subtypes/strains. For this, two other interactomes, describing the murine host response against H5N1 and H1N1pdm, were constructed, which in turn validated many of the observed interactions (in the period day 1-day 7). The H1N1 interactome revealed the role of cell cycle both in innate and adaptive immunity (day 1-day 14). Also, pathogen sensory pathways (e.g., RIG-I) displayed long-lasting association with cytokine/chemokine signaling (until day 8). Interestingly, the above observations were also supported by the H5N1 and H1N1pdm models. It also elucidated the enhanced coupling of the activated innate pathways with the suppressed PPAR signaling to keep low inflammation until viral clearance (until day 14). Further, it showed that interactions reflecting phagocytosis processes continued long after the viral clearance and the establishment of adaptive immunity (day 8-day 40). Additionally, interactions involving B cell receptor pathway were evident since day 1. These results collectively inform the emerging field of public health omics and future clinical studies aimed at deciphering dynamic host responses to infectious agents.

Tamoxifen integromics and personalized medicine: dynamic modular transformations underpinning response to tamoxifen in breast cancer treatment.

Recent advances in pharmacogenomics technologies allow bold steps to be taken towards personalized medicine, more accurate health planning, and personalized drug development. In this framework, systems pharmacology network-based approaches offer an appealing way for integrating multi-omics data and set the basis for defining systems-level drug response biomarkers. On the road to individualized tamoxifen treatment in estrogen receptor-positive breast cancer patients, we examine the dynamics of the attendant pharmacological response mechanisms. By means of an "integromics" network approach, we assessed the tamoxifen effect through the way the high-order organization of interactome (i.e., the modules) is perturbed. To accomplish that, first we integrated the time series transcriptome data with the human protein interaction data, and second, an efficient module-detecting algorithm was applied onto the composite graphs. Our findings show that tamoxifen induces severe modular transformations on specific areas of the interactome. Our modular biomarkers in response to tamoxifen attest to the immunomodulatory role of tamoxifen, and further reveal that it deregulates cell cycle and apoptosis pathways, while coordinating the proteasome and basal transcription factors. To the best of our knowledge, this is the first report that informs the fields of personalized medicine and clinical pharmacology about the actual dynamic interactome response to tamoxifen administration.

Supervised method for construction of microRNA-mRNA networks: application in cardiac tissue aging dataset.

MicroRNAs play an important role in regulation of gene expression, but still detection of their targets remains a challenge. In this work we present a supervised regulatory network inference method with aim to identify potential target genes (mRNAs) of microRNAs. Briefly, the proposed method exploiting mRNA and microRNA expression trains Random Forests on known interactions and subsequently it is able to predict novel ones. In parallel, we incorporate different available data sources, such as Gene Ontology and ProteinProtein Interactions, to deliver biologically consistent results. Application in both benchmark data and an experiment studying aging showed robust performance.

Multi-scale modeling of gene regulatory networks via integration of temporal and topological biological data.

Regulome is the dynamic network representation of the regulatory interplay among genes, proteins and other cellular components that control cellular processes. Reconstruction of gene regulatory networks (GRN) delineates one of the main objectives of Systems Biology towards understanding the organization of regulome. Significant progress has been reported the last years regarding GRN reconstruction methods, but the majority of them either consider information originating solely from gene expression data or/and are applied on a small fraction of the experimental dataset. In this paper, we will describe an integrative method, utilizing both temporal information arriving from time-series gene expression profiles, as well as topological properties of protein networks. The proposed methodology detects relations among either groups of genes or specific genes depending on the level of abstraction or resolution requested. Application on real data proved the ability of the method to extract relations in accordance with current biological knowledge as well as discriminate between different experimental conditions.

Revealing the dynamic modularity of composite biological networks in breast cancer treatment.

A major challenge in modern breast cancer treatment is to unravel the effect of drug activity through the systematic rewiring of cellular networks over time. Here, we illustrate the efficacy and discriminative power of our integrative approach in detecting modules that represent the regulatory effect of tamoxifen, widely used in anti-estrogen treatment, on transcriptome and proteome and serve as dynamic sub-network signatures. Initially, composite networks, after integrating protein interaction and time series gene expression data between two conditions (estradiol and estradiol plus tamoxifen), were constructed. Further, the Detect Module from Seed Protein (DMSP) algorithm elaborated on the graphs and constructed modules, with specific 'seed' proteins used as starting points. Our findings provide evidence about the way drugs perturb and rewire the high-order organization of interactome in time.

Dynamic gene network reconstruction from gene expression data in mice after influenza A (H1N1) infection.

BACKGROUND: The immune response to viral infection is a temporal process, represented by a dynamic and complex network of gene and protein interactions. Here, we present a reverse engineering strategy aimed at capturing the temporal evolution of the underlying Gene Regulatory Networks (GRN). The proposed approach will be an enabling step towards comprehending the dynamic behavior of gene regulation circuitry and mapping the network structure transitions in response to pathogen stimuli. RESULTS: We applied the Time Varying Dynamic Bayesian Network (TV-DBN) method for reconstructing the gene regulatory interactions based on time series gene expression data for the mouse C57BL/6J inbred strain after infection with influenza A H1N1 (PR8) virus. Initially, 3500 differentially expressed genes were clustered with the use of k-means algorithm. Next, the successive in time GRNs were built over the expression profiles of cluster centroids. Finally, the identified GRNs were examined with several topological metrics and available protein-protein and protein-DNA interaction data, transcription factor and KEGG pathway data. CONCLUSIONS: Our results elucidate the potential of TV-DBN approach in providing valuable insights into the temporal rewiring of the lung transcriptome in response to H1N1 virus.

A contextual data mining approach toward assisting the treatment of anxiety disorders.

Anxiety disorders are considered the most prevalent of mental disorders. Nevertheless, the exact reasons that provoke them to patients remain yet not clearly specified, while the literature concerning the environment for monitoring and treatment support is rather scarce warranting further investigation. Toward this direction, in this study a context-aware approach is proposed, aiming to provide medical supervisors with a series of applications and personalized services targeted to exploit the multiparameter contextual data collected through a long-term monitoring procedure. More specifically, an application that assists the archiving and retrieving of the patients' health records was developed, and four treatment supportive services were considered. The three of them focus on the discovery of possible associations between the patient's contextual data; the last service aims at predicting the stress level a patient might suffer from, in a given context. The proposed approach was experimentally evaluated quantitatively (in terms of computational efficiency and time requirements) and qualitatively by experts on the field of mental health domain. The feedback received was very encouraging and the proposed approach seems quite useful to the anxiety disorders' treatment.

Leveraging dynamic user profiles for the assistance of anxiety disorders' treatment using inferential rules.

While anxiety disorders exhibit an impressive spread especially in western societies, context-awareness seems a promising technology to provide assistance to physicians in psychotherapy sessions. In the present paper an approach addressing the assistance of the anxiety disorders' treatment is proposed. The suggested method employs the a priori association rule mining algorithm in order to achieve dynamic update of patient profiles according to generated rules describing the underlying relations between patients' main context conditions and their stress level. This method was evaluated by therapists specializing in the mental health domain and the feedback received was very encouraging with respect to the assistance dynamic patient profiles offer, during CBT sessions.