Hubba: hub objects analyzer—a framework of interactome hubs identification for network biology

Lin, Chung Yen; Chin, Chia Hao; Wu, Hsin Hung; Chen, Shu Hwa; Ho, Chin Wen; Ko, Ming-Tat

doi:10.1093/nar/gkn257

Cited by 230 publications

(194 citation statements)

References 29 publications

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“…Network graphs were visualized using the software plugin Cerebral (29) to appreciate network directionality within the cell. Hub degree (the number of protein-level interactions with other members of the network) was determined for each gene "node" in the network using the software plugin cytoHubba for Cytoscape (30).…”

Section: Gene-expression Microarray Data Processing and Network Analysismentioning

confidence: 99%

Functional Genetic Variation inNFKBIAand Susceptibility to Childhood Asthma, Bronchiolitis, and Bronchopulmonary Dysplasia

Ali

Hirschfeld

Mayer

et al. 2013

The Journal of Immunology

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Respiratory diseases are the most frequent chronic illnesses in babies and children. Although a vigorous innate immune system is critical for maintaining lung health, a balanced response is essential to minimize damaging inflammation. We investigated the functional and clinical impact of human genetic variants in the promoter of NFKBIA, which encodes IκBα, the major negative regulator of NF-κB. In this study, we quantified the functional impact of NFKBIA promoter polymorphisms (rs3138053, rs2233406, and rs2233409) on promoter-driven protein expression, allele-specific and total NFKBIA mRNA expression, IκBα protein expression, and TLR responsiveness; mapped innate immune regulatory networks active during respiratory syncytial virus infection, asthma, and bronchopulmonary dysplasia; and genotyped and analyzed independent cohorts of children with respiratory syncytial virus infection, asthma, and bronchopulmonary dysplasia. Genetic variants in the promoter of NFKBIA influenced NFKBIA gene expression, IκBα protein expression, and TLR-mediated inflammatory responses. Using a systems biology approach, we demonstrated that NFKBIA/IκBα is a central hub in transcriptional responses of prevalent childhood lung diseases, including respiratory syncytial virus infection, asthma, and bronchopulmonary dysplasia. Finally, by examining independent pediatric lung disease cohorts, we established that this immunologically relevant genetic variation in the promoter of NFKBIA is associated with differential susceptibility to severe bronchiolitis following infection with respiratory syncytial virus, airway hyperresponsiveness, and severe bronchopulmonary dysplasia. These data highlight the importance of negative innate immune regulators, such as NFKBIA, in pediatric lung disease and begin to unravel common aspects in the genetic predisposition to bronchopulmonary dysplasia, bronchiolitis, and childhood asthma.

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Section: Gene-expression Microarray Data Processing and Network Analysismentioning

confidence: 99%

Functional Genetic Variation inNFKBIAand Susceptibility to Childhood Asthma, Bronchiolitis, and Bronchopulmonary Dysplasia

Ali

Hirschfeld

Mayer

et al. 2013

The Journal of Immunology

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“…The subgraph centrality has been previously applied to the identification of essential proteins in proteomic maps (Estrada, 2006a;2006b;Zotenko et al, 2008;Lin et al, 2008;Gursoy et al, 2008) and the characterization of malignant tissues (Platzer et al, 2007). It has also been applied to the study of weighted graphs to account for the degree of folding of protein chains (see for instance Estrada, 2002;2004) as well as to describe the molecular structure of drug-like and environmentally relevant organic compounds (for a review see Estrada and Uriarte, 2001).…”

Section: Study Of Protein-protein Interaction Networkmentioning

confidence: 99%

Generalized walks-based centrality measures for complex biological networks

Estrada

2010

Journal of Theoretical Biology

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A strategy for zooming in and out the topological environment of a node in a complex network is developed. This approach is applied here to generalize the subgraph centrality of nodes in complex networks. In this case the zooming in strategy is based on the use of some known matrix functions which allow focusing locally on the environment of a node. When a zooming out strategy is applied new matrix functions are introduced, which give a more global picture of the topological surrounds of a node. These indices permit a modulation of the scales at which the environment of a node influences its centrality. We apply them to the study of 10 protein-protein interaction (PPI) networks. We illustrate the similarities and differences between the generalized subgraph centrality indices as well as among them and some classical centrality measures. We show here that the use of centrality indices based on the zooming in strategy identifies a larger number of essential proteins in the yeast PPI network than any of the other centrality measures studied.

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“…72,73 We performed network properties assessment using the Cytoscape plugin "CytoHubba" (http://www.jsbi.org/pdfs/journal1/GIW09/ Poster/GIW09S003.pdf) to provide a topological analysis and allow the definition of a range of network properties which could be further used to evaluate the "essentiality" of the network nodes. The top 10 of the gene regulation network nodes ranked for their MCC (Maximal Clique Centrality) scores were used to generate a minimal essential network (MEN).…”

Section: Minimal Essential Networkmentioning

confidence: 99%

The oncogenic FIP1L1-PDGFRαfusion protein displays skewed signaling properties compared to its wild-type PDGFRαcounterpart

et al. 2015

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ABSTRACT. Aberrant activation of oncogenic kinases is frequently observed in human cancers, but the underlying mechanism and resulting effects on global signaling are incompletely understood. Here, we demonstrate that the oncogenic FIP1L1-PDGFRa kinase exhibits a significantly different signaling pattern compared to its PDGFRa wild type counterpart. Interestingly, the activation of primarily membrane-based signal transduction processes (such as PI3-kinase-and MAP-kinase-pathways) is remarkably shifted toward a prominent activation of STAT factors. This diverging signaling pattern compared to classical PDGF-receptor signaling is partially coupled to the aberrant cytoplasmic localization of the oncogene, since membrane targeting of FIP1L1-PDGFRa restores activation of MAPK-and PI3K-pathways. In stark contrast to the classical cytokine-induced STAT activation process, STAT activation by FIP1L1-PDGFRa does neither require Janus kinase activity nor Src kinase activity. Furthermore, we investigated the mechanism of STAT5 activation via FIP1L1-PDGFRa in more detail and found that STAT5 activation does not involve an SH2-domain-mediated binding mechanism. We thus demonstrate that STAT5 activation occurs via a non-canonical activation mechanism in which STAT5 may be subject to a direct phosphorylation by FIP1L1-PDGFRa.

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Hubba: hub objects analyzer—a framework of interactome hubs identification for network biology

Cited by 230 publications

References 29 publications

Functional Genetic Variation inNFKBIAand Susceptibility to Childhood Asthma, Bronchiolitis, and Bronchopulmonary Dysplasia

Functional Genetic Variation inNFKBIAand Susceptibility to Childhood Asthma, Bronchiolitis, and Bronchopulmonary Dysplasia

Generalized walks-based centrality measures for complex biological networks

The oncogenic FIP1L1-PDGFRαfusion protein displays skewed signaling properties compared to its wild-type PDGFRαcounterpart

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