Bioinformatic Approach to Identify Chaperone Pathway Relationship from Large-Scale Interaction Networks

Author(s):  
Yunchen Gong ◽  
Zhaolei Zhang ◽  
Walid A. Houry
2017 ◽  
Author(s):  
Vladimir Gligorijević ◽  
Meet Barot ◽  
Richard Bonneau

AbstractThe prevalence of high-throughput experimental methods has resulted in an abundance of large-scale molecular and functional interaction networks. The connectivity of these networks provide a rich source of information for inferring functional annotations for genes and proteins. An important challenge has been to develop methods for combining these heterogeneous networks to extract useful protein feature representations for function prediction. Most of the existing approaches for network integration use shallow models that cannot capture complex and highly-nonlinear network structures. Thus, we propose deepNF, a network fusion method based on Multimodal Deep Autoencoders to extract high-level features of proteins from multiple heterogeneous interaction networks. We apply this method to combine STRING networks to construct a common low-dimensional representation containing high-level protein features. We use separate layers for different network types in the early stages of the multimodal autoencoder, later connecting all the layers into a single bottleneck layer from which we extract features to predict protein function. We compare the cross-validation and temporal holdout predictive performance of our method with state-of-the-art methods, including the recently proposed method Mashup. Our results show that our method outperforms previous methods for both human and yeast STRING networks. We also show substantial improvement in the performance of our method in predicting GO terms of varying type and specificity.AvailabilitydeepNF is freely available at: https://github.com/VGligorijevic/deepNF


2020 ◽  
Author(s):  
Diogo Borges Lima ◽  
Ying Zhu ◽  
Fan Liu

ABSTRACTSoftware tools that allow visualization and analysis of protein interaction networks are essential for studies in systems biology. One of the most popular network visualization tools in biology is Cytoscape, which offers a large selection of plugins for interpretation of protein interaction data. Chemical cross-linking coupled to mass spectrometry (XL-MS) is an increasingly important source for such interaction data, but there are currently no Cytoscape tools to analyze XL-MS results. In light of the suitability of Cytoscape platform but also to expand its toolbox, here we introduce XlinkCyNET, an open-source Cytoscape Java plugin for exploring large-scale XL-MS-based protein interaction networks. XlinkCyNET offers rapid and easy visualization of intra and intermolecular cross-links and the locations of protein domains in a rectangular bar style, allowing subdomain-level interrogation of the interaction network. XlinkCyNET is freely available from the Cytoscape app store: http://apps.cytoscape.org/apps/xlinkcynet and at https://www.theliulab.com/software/xlinkcynet.


2018 ◽  
Author(s):  
Marcus A. M. de Aguiar ◽  
Erica A. Newman ◽  
Mathias M. Pires ◽  
Justin D. Yeakel ◽  
David H. Hembry ◽  
...  

AbstractThe structure of ecological interactions is commonly understood through analyses of interaction networks. However, these analyses may be sensitive to sampling biases in both the interactors (the nodes of the network) and interactions (the links between nodes), because the detectability of species and their interactions is highly heterogeneous. These issues may affect the accuracy of empirically constructed ecological networks. Yet statistical biases introduced by sampling error are difficult to quantify in the absence of full knowledge of the underlying ecological network’s structure. To explore properties of large-scale modular networks, we developed EcoNetGen, which constructs and samples networks with predetermined topologies. These networks may represent a wide variety of communities that vary in size and types of ecological interactions. We sampled these networks with different sampling designs that may be employed in field observations. The observed networks generated by each sampling process were then analyzed with respect to the number of components, size of components and other network metrics. We show that the sampling effort needed to estimate underlying network properties accurately depends both on the sampling design and on the underlying network topology. In particular, networks with random or scale-free modules require more complete sampling to reveal their structure, compared to networks whose modules are nested or bipartite. Overall, the modules with nested structure were the easiest to detect, regardless of sampling design. Sampling according to species degree (number of interactions) was consistently found to be the most accurate strategy to estimate network structure. Conversely, sampling according to module (representing different interaction types or taxa) results in a rather complete view of certain modules, but fails to provide a complete picture of the underlying network. We recommend that these findings be incorporated into field sampling design of projects aiming to characterize large species interactions networks to reduce sampling biases.Author SummaryEcological interactions are commonly modeled as interaction networks. Analyses of such networks may be sensitive to sampling biases and detection issues in both the interactors and interactions (nodes and links). Yet, statistical biases introduced by sampling error are difficult to quantify in the absence of full knowledge of the underlying network’s structure. For insight into ecological networks, we developed software EcoNetGen (available in R and Python). These allow the generation and sampling of several types of large-scale modular networks with predetermined topologies, representing a wide variety of communities and types of ecological interactions. Networks can be sampled according to designs employed in field observations. We demonstrate, through first uses of this software, that underlying network topology interacts strongly with empirical sampling design, and that constructing empirical networks by starting with highly connected species may be the give the best representation of the underlying network.


2013 ◽  
Vol 42 (D1) ◽  
pp. D92-D97 ◽  
Author(s):  
Jun-Hao Li ◽  
Shun Liu ◽  
Hui Zhou ◽  
Liang-Hu Qu ◽  
Jian-Hua Yang

Author(s):  
Paul Giguere ◽  
Scott W. Formica ◽  
Wayne M. Harding ◽  
Michele R. Cummins

Designing online trainings or courses for large numbers of participants can prove to be challenging for instructors and facilitators. Online learning environments need to be structured in a way that preserves actual or perceived levels of interaction, participant perceptions of value and utility, and achievement of the learning objectives. This chapter describes five Large-Scale Interaction Strategies that offer guidance for addressing some of these online instructional design issues. Evaluation data are presented in support of two of the strategies, and recommendations are provided about how future research in this area might be conducted.


2019 ◽  
Vol 20 (S24) ◽  
Author(s):  
Jon P. Klein ◽  
Zhifu Sun ◽  
Nathan P. Staff

Abstract Background Emerging evidence suggests retroviruses play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). Specifically, activation of ancient viral genes embedded in the human genome is theorized to lead to motor neuron degeneration. We explore whether connections exist between ALS and retroviruses through protein interaction networks (PIN) and pathway analysis, and consider the potential roles in drug target discovery. Protein database and pathway/network analytical software including Ingenuity Pathway BioProfiler, STRING, and CytoScape were utilized to identify overlapping protein interaction networks and extract core cluster (s) of retroviruses and ALS. Results Topological and statistical analysis of the ALS-PIN and retrovirus-PIN identified a shared, essential protein network and a core cluster with significant connections with both networks. The identified core cluster has three interleukin molecules IL10, Il-6 and IL-1B, a central apoptosis regulator TP53, and several major transcription regulators including MAPK1, ANXA5, SQSTM1, SREBF2, and FADD. Pathway enrichment analysis showed that this core cluster is associated with the glucocorticoid receptor singling and neuroinflammation signaling pathways. For confirmation purposes, we applied the same methodology to the West Nile and Polio virus, which demonstrated trivial connectivity with ALS, supporting the unique connection between ALS and retroviruses. Conclusions Bioinformatics analysis provides evidence to support pathological links between ALS and retroviral activation. The neuroinflammation and apoptotic regulation pathways are specifically implicated. The continuation and further analysis of large scale genome studies may prove useful in exploring genes important in retroviral activation and ALS, which may help discover new drug targets.


2014 ◽  
Vol 111 (7) ◽  
pp. 2542-2547 ◽  
Author(s):  
Y. Ivarsson ◽  
R. Arnold ◽  
M. McLaughlin ◽  
S. Nim ◽  
R. Joshi ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Gaston K. Mazandu ◽  
Nicola J. Mulder

Technological developments in large-scale biological experiments, coupled with bioinformatics tools, have opened the doors to computational approaches for the global analysis of whole genomes. This has provided the opportunity to look at genes within their context in the cell. The integration of vast amounts of data generated by these technologies provides a strategy for identifying potential drug targets within microbial pathogens, the causative agents of infectious diseases. As proteins are druggable targets, functional interaction networks between proteins are used to identify proteins essential to the survival, growth, and virulence of these microbial pathogens. Here we have integrated functional genomics data to generate functional interaction networks between Mycobacterium tuberculosis proteins and carried out computational analyses to dissect the functional interaction network produced for identifying drug targets using network topological properties. This study has provided the opportunity to expand the range of potential drug targets and to move towards optimal target-based strategies.


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