Community Landscapes: An Integrative Approach to Determine Overlapping Network Module Hierarchy, Identify Key Nodes and Predict Network Dynamics

Kovács, I.; Palotai, Robin; Szalay, Máté; Csermely, Péter

doi:10.1371/journal.pone.0012528

Cited by 180 publications

(195 citation statements)

References 297 publications

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“…Yet another technique for assessing overlapping communities, ModuLand, determines community structure by assessing node influence where nodes are considered to share a module if they mutually have large influence (Kovács et al, 2010). Module centers are determined by nodes with higher levels of mutual influence (i.e., more highly interconnected nodes influence each other more) with nodes with less influence forming the periphery.…”

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confidence: 99%

The Brain as a Complex System: Using Network Science as a Tool for Understanding the Brain

et al. 2011

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Although graph theory has been around since the 18th century, the field of network science is more recent and continues to gain popularity, particularly in the field of neuroimaging. The field was propelled forward when Watts and Strogatz introduced their small-world network model, which described a network that provided regional specialization with efficient global information transfer. This model is appealing to the study of brain connectivity, as the brain can be viewed as a system with various interacting regions that produce complex behaviors. In practice, graph metrics such as clustering coefficient, path length, and efficiency measures are often used to characterize system properties. Centrality metrics such as degree, betweenness, closeness, and eigenvector centrality determine critical areas within the network. Community structure is also essential for understanding network organization and topology. Network science has led to a paradigm shift in the neuroscientific community, but it should be viewed as more than a simple ''tool du jour.'' To fully appreciate the utility of network science, a greater understanding of how network models apply to the brain is needed. An integrated appraisal of multiple network analyses should be performed to better understand network structure rather than focusing on univariate comparisons to find significant group differences; indeed, such comparisons, popular with traditional functional magnetic resonance imaging analyses, are arguably no longer relevant with graph-theory based approaches. These methods necessitate a philosophical shift toward complexity science. In this context, when correctly applied and interpreted, network scientific methods have a chance to revolutionize the understanding of brain function.

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confidence: 99%

The Brain as a Complex System: Using Network Science as a Tool for Understanding the Brain

et al. 2011

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“…Understanding the complexity of molecular networks is an important challenge to the post-genomic era. The function of biomolecular function is often dependent on modularization, the network module which is made by a number of nodes in conjunction with each other and has a stable structure which can often reflect a similar nature between nodes (Chen et al, 2010; Kovács et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Construction of a Protein-Protein Interaction Network for Chronic Myelocytic Leukemia and Pathway Prediction of Molecular Complexes

Zhou

Teng²,

Yang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Asian Pac J Cancer Prev, 15 (13), [5325][5326][5327][5328][5329][5330] IntroductionChronic myelogenous leukemia (CML) is a kind of chronic myeloproliferative disorders of primitive pluripotent hematopoietic stem cells. The special cytogenetic features of Chronic myelogenous leukemia cells is Philadelphia chromosome t (9; 22) (q34; q11). The proto-oncogene c-ABL in the long arm of Chromosome 9 translocates to the breakpoint cluster pool (BCR) of the long arm of chromosome 22 , formating fusion gene BCR-ABL. Which encodes a protein having a strong activity of tyrosinase. The tyrosine kinase pathway can be phosphorylated by a variety of genes such as RAS, myc, c-CBL, phthalocyanine inositol phospholipid 3 'kinase, and NF-kB. Downstream of tyrosinase stimulation is the expression of oncogenes including c-fos, c-jun, etc. which stimulate cell non-growth factor-dependent proliferation and block apoptosis eventually leading to uncontrolled cell proliferation. BCR-ABL gene is considered as the molecular basis of the pathogenesis of CML and as an effective indicator diagnosis, efficacy, prognosis.

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“…Network generation and processing was performed using Cytoscape 2.8.3 (Smoot, Ono, Ruscheinski, Wang, & Ideker, 2011). A hierarchy of interacting network modules within the interactome models was constructed using the ModuLand plugin for Cytoscape 2.8.3 (Kovacs, Palotai, Szalay, & Csermely, 2010; Szalay‐Bekő et al, 2012). The central core unit of each network module (metanode) was defined as the 10 most central genes.…”

Section: Methodsmentioning

confidence: 99%

NF‐Y‐dependent regulation of glutamate receptor 4 expression and cell survival in cells of the oligodendrocyte lineage

Begum

Otsu

Ahmed

et al. 2018

Glia

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Glutamate receptor subunit 4 (GluA4) is highly expressed by neural cells sensitive to excitotoxicity, and is the predominant subunit expressed by oligodendrocyte precursor cells (OPC) during a key period of vulnerability to hypoxic‐ischemic injury. Therefore, transcriptional networks downstream of excitotoxic GluA4 activation represent a promising area for therapeutic intervention. In this work, we identify the CCAAT binding transcription factor NF‐Yb as a novel transcriptional regulator of Gria4 (GluA4 gene), and a controller of excitotoxic death in the oligodendroglial lineage. We describe a novel regulatory region within Gria4 containing CCAAT sequences whose binding by NF‐Yb is regulated by excitotoxicity. Excitotoxicity‐induced alterations in NF‐Yb binding are associated with changes in Gria4 transcription, while knockdown of NF‐Yb alters the transcription of reporter constructs containing this regulatory region. Data from immortalized and primary OPC reveal that RNAi and pharmacological disruption of NF‐Yb alter Gria4 transcription, with the latter inducing apoptosis and influencing a set of apoptotic genes similarly regulated during excitotoxicity. These data provide the first definition of a trans‐acting mechanism regulating Gria4, and identify the NF‐Y network as a potential source of pharmacological targets for promoting OPC survival.

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Community Landscapes: An Integrative Approach to Determine Overlapping Network Module Hierarchy, Identify Key Nodes and Predict Network Dynamics

Cited by 180 publications

References 297 publications

The Brain as a Complex System: Using Network Science as a Tool for Understanding the Brain

The Brain as a Complex System: Using Network Science as a Tool for Understanding the Brain

Construction of a Protein-Protein Interaction Network for Chronic Myelocytic Leukemia and Pathway Prediction of Molecular Complexes

NF‐Y‐dependent regulation of glutamate receptor 4 expression and cell survival in cells of the oligodendrocyte lineage

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