Project description:Existing software tools for topology-based pathway enrichment analysis are either computationally inefficient, have undesirable statistical power, or require expert knowledge to leverage the methods' capabilities. To address these limitations, we have overhauled NetGSA, an existing topology-based method, to provide a computationally-efficient user-friendly tool that offers interactive visualization. Pathway enrichment analysis for thousands of genes can be performed in minutes on a personal computer without sacrificing statistical power. The new software also removes the need for expert knowledge by directly curating gene-gene interaction information from multiple external databases. Lastly, by utilizing the capabilities of Cytoscape, the new software also offers interactive and intuitive network visualization.
Project description:We here used the technology of RNA interference or selective treatment of the ESR1 and cDNA microarrays to reconstruct a network between genes known to be disregulated in ER-positive breast cancer diseases. Therefor single genes of high importance were silenced and the effect of this pertubation was measured with cDNA microarrays. Keywords: Network Reconstruction, RNAi, siRNA, Interaction Network human ER-positive breast cancer cell line was cultivated as described and transfection with chemically synthesized siRNAs was performed according to standard HiPerFect transfection protocol by Qiagen (Hilden, Germany) At least 4 cDNA-microarrays were hybridized in dye-swap method for the silencing of every gene of interest. To minimize off-target effects we used at least two different siRNAs per gene.
Project description:An essential step in the analysis of agent-based simulation is sensitivity analysis, which namely examines the dependency of parameter values on simulation results. Although a number of approaches have been proposed for sensitivity analysis, they still have limitations in exhaustivity and interpretability. In this study, we propose a novel methodology for sensitivity analysis of agent-based simulation, MASSIVE (Massively parallel Agent-based Simulations and Subsequent Interactive Visualization-based Exploration). MASSIVE takes a unique paradigm, which is completely different from those of sensitivity analysis methods developed so far, By combining massively parallel computation and interactive data visualization, MASSIVE enables us to inspect a broad parameter space intuitively. We demonstrated the utility of MASSIVE by its application to cancer evolution simulation, which successfully identified conditions that generate heterogeneous tumors. We believe that our approach would be a de facto standard for sensitivity analysis of agent-based simulation in an era of evergrowing computational technology. All the results form our MASSIVE analysis are available at https://www.hgc.jp/~niiyan/massive.
Project description:The rapid accumulation of biological networks poses new challenges and calls for powerful integrative analysis tools. Most existing methods capable of simultaneously analyzing a large number of networks were primarily designed for unweighted networks, and cannot easily be extended to weighted networks. However, it is known that transforming weighted into unweighted networks by dichotomizing the edges of weighted networks with a threshold generally leads to information loss. We have developed a novel, tensor-based computational framework for mining recurrent heavy subgraphs in a large set of massive weighted networks. Specifically, we formulate the recurrent heavy subgraph identification problem as a heavy 3D subtensor discovery problem with sparse constraints. We describe an effective approach to solving this problem by designing a multi-stage, convex relaxation protocol, and a non-uniform edge sampling technique. We applied our method to 130 co-expression networks, and identified 11,394 recurrent heavy subgraphs, grouped into 2,810 families. We demonstrated that the identified subgraphs represent meaningful biological modules by validating against a large set of compiled biological knowledge bases. We also showed that the likelihood for a heavy subgraph to be meaningful increases significantly with its recurrence in multiple networks, highlighting the importance of the integrative approach to biological network analysis. Moreover, our approach based on weighted graphs detects many patterns that would be overlooked using unweighted graphs. In addition, we identified a large number of modules that occur predominately under specific phenotypes. This analysis resulted in a genome-wide mapping of gene network modules onto the phenome. Finally, by comparing module activities across many datasets, we discovered high-order dynamic cooperativeness in protein complex networks and transcriptional regulatory networks.
Project description:BACKGROUND:Structural data from crystallographic analyses contain a vast amount of information on protein-protein contacts. Knowledge on protein-protein interactions is essential for understanding many processes in living cells. The methods to investigate these interactions range from genetics to biophysics, crystallography, bioinformatics and computer modeling. Also crystal contact information can be useful to understand biologically relevant protein oligomerisation as they rely in principle on the same physico-chemical interaction forces. Visualization of crystal and biological contact data including different surface properties can help to analyse protein-protein interactions. RESULTS:VASCo is a program package for the calculation of protein surface properties and the visualization of annotated surfaces. Special emphasis is laid on protein-protein interactions, which are calculated based on surface point distances. The same approach is used to compare surfaces of two aligned molecules. Molecular properties such as electrostatic potential or hydrophobicity are mapped onto these surface points. Molecular surfaces and the corresponding properties are calculated using well established programs integrated into the package, as well as using custom developed programs. The modular package can easily be extended to include new properties for annotation. The output of the program is most conveniently displayed in PyMOL using a custom-made plug-in. CONCLUSION:VASCo supplements other available protein contact visualisation tools and provides additional information on biological interactions as well as on crystal contacts. The tool provides a unique feature to compare surfaces of two aligned molecules based on point distances and thereby facilitates the visualization and analysis of surface differences.
Project description:Proxima is a molecular perception library designed with a double purpose: to be used with immersive molecular viewers (thus providing any required feature not supported by third party libraries) and to be integrated in workflow managers thus providing the functionalities needed for the first steps of molecular modeling studies. It thus stands at the boundary between visualization and computation. The purpose of the present article is to provide a general introduction to the first release of Proxima, describe its most significant features, and highlight its performance by means of some case studies. The current version of Proxima is available for evaluation purposes at https://bitbucket.org/sns-smartlab/proxima/src/master/.
Project description:Supervised neural networks have been applied as a machine learning technique to identify and predict emergent patterns among multiple variables. A common criticism of these methods is the inability to characterize relationships among variables from a fitted model. Although several techniques have been proposed to "illuminate the black box", they have not been made available in an open-source programming environment. This article describes the NeuralNetTools package that can be used for the interpretation of supervised neural network models created in R. Functions in the package can be used to visualize a model using a neural network interpretation diagram, evaluate variable importance by disaggregating the model weights, and perform a sensitivity analysis of the response variables to changes in the input variables. Methods are provided for objects from many of the common neural network packages in R, including caret, neuralnet, nnet, and RSNNS. The article provides a brief overview of the theoretical foundation of neural networks, a description of the package structure and functions, and an applied example to provide a context for model development with NeuralNetTools. Overall, the package provides a toolset for neural networks that complements existing quantitative techniques for data-intensive exploration.
Project description:Unlabelled: The ability to experimentally determine molecular interactions on an almost proteome-wide scale under different conditions is enabling researchers to move from static to dynamic network analysis, uncovering new insights into how interaction networks are physically rewired in response to different stimuli and in disease. Dynamic interaction data presents a special challenge in network biology. Here, we present DyNet, a Cytoscape application that provides a range of functionalities for the visualization, real-time synchronization and analysis of large multi-state dynamic molecular interaction networks enabling users to quickly identify and analyze the most 'rewired' nodes across many network states.Availability and implementationDyNet is available at the Cytoscape (3.2+) App Store (http://apps.cytoscape.org/apps/dynet).Contactdavid.lynn@sahmri.comSupplementary informationSupplementary data are available at Bioinformatics online.
Project description:Artificial Neural Networks (ANNs) are bio-inspired models of neural computation that have proven highly effective. Still, ANNs lack a natural notion of time, and neural units in ANNs exchange analog values in a frame-based manner, a computationally and energetically inefficient form of communication. This contrasts sharply with biological neurons that communicate sparingly and efficiently using isomorphic binary spikes. While Spiking Neural Networks (SNNs) can be constructed by replacing the units of an ANN with spiking neurons (Cao et al., 2015; Diehl et al., 2015) to obtain reasonable performance, these SNNs use Poisson spiking mechanisms with exceedingly high firing rates compared to their biological counterparts. Here we show how spiking neurons that employ a form of neural coding can be used to construct SNNs that match high-performance ANNs and match or exceed state-of-the-art in SNNs on important benchmarks, while requiring firing rates compatible with biological findings. For this, we use spike-based coding based on the firing rate limiting adaptation phenomenon observed in biological spiking neurons. This phenomenon can be captured in fast adapting spiking neuron models, for which we derive the effective transfer function. Neural units in ANNs trained with this transfer function can be substituted directly with adaptive spiking neurons, and the resulting Adaptive SNNs (AdSNNs) can carry out competitive classification in deep neural networks without further modifications. Adaptive spike-based coding additionally allows for the dynamic control of neural coding precision: we show empirically how a simple model of arousal in AdSNNs further halves the average required firing rate and this notion naturally extends to other forms of attention as studied in neuroscience. AdSNNs thus hold promise as a novel and sparsely active model for neural computation that naturally fits to temporally continuous and asynchronous applications.
Project description:Deep brain stimulation (DBS) is an established treatment for movement disorders such as Parkinson's disease or essential tremor. Currently, the selection of optimal stimulation settings is performed by iteratively adjusting the stimulation parameters and is a time consuming procedure that requires multiple clinic visits of several hours. Recently, computational models to predict and visualize the effect of DBS have been developed with the goal to simplify and accelerate this procedure by providing visual guidance and such models have been made available also on mobile devices. However, currently available visualization software still either lacks mobility, i.e., it is running on desktop computers and not easily available in clinical praxis, or flexibility, as the simulations that are visualized on mobile devices have to be precomputed. The goal of the pipeline presented in this paper is to close this gap: Using Duality, a newly developed software for the interactive visualization of simulation results, we implemented a pipeline that allows to compute DBS simulations in near-real time and instantaneously visualize the result on a tablet computer. Therefore, a client-server setup is used, so that the visualization and user interaction occur on the tablet computer, while the computations are carried out on a remote server. We present two examples for the use of Duality, one for postoperative programming and one for the planning of DBS surgery in a pre- or intraoperative setting. We carry out a performance analysis and present the results of a case study in which the pipeline for postoperative programming was applied.