Network Analysis Reveals Functional Cross-links between Disease and Inflammation Genes

Zhang, Yunpeng; Fan, Huihui; Xu, Juan; Xiao, Yun; Xu, Yanjun; Li, Yixue; Li, Xia

doi:10.1038/srep03426

Cited by 23 publications

(14 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition to those directly overlapping nodes and edges serving as versatile players underlying the link between inflammation and cancer, we also explored other alternative approaches that inflammation might contribute to cancer in esophagus. Significant crosstalk module pairs of inflammation and cancer were thus determined based on permutation test, via randomizing PPI network with degree distribution of nodes keeping unchanged 1000 times 24 25 . With a p value cutoff of 0.05, we identified 402 significant crosstalk pairs in total ( Supplementary Table 4 ).…”

Section: Resultsmentioning

confidence: 99%

A functional module-based exploration between inflammation and cancer in esophagus

Liu

Huang

et al. 2015

Sci Rep

Self Cite

View full text Add to dashboard Cite

Inflammation contributing to the underlying progression of diverse human cancers has been generally appreciated, however, explorations into the molecular links between inflammation and cancer in esophagus are still at its early stage. In our study, we presented a functional module-based approach, in combination with multiple data resource (gene expression, protein-protein interactions (PPI), transcriptional and post-transcriptional regulations) to decipher the underlying links. Via mapping differentially expressed disease genes, functional disease modules were identified. As indicated, those common genes and interactions tended to play important roles in linking inflammation and cancer. Based on crosstalk analysis, we demonstrated that, although most disease genes were not shared by both kinds of modules, they might act through participating in the same or similar functions to complete the molecular links. Additionally, we applied pivot analysis to extract significant regulators for per significant crosstalk module pair. As shown, pivot regulators might manipulate vital parts of the module subnetworks, and then work together to bridge inflammation and cancer in esophagus. Collectively, based on our functional module analysis, we demonstrated that shared genes or interactions, significant crosstalk modules, and those significant pivot regulators were served as different functional parts underlying the molecular links between inflammation and cancer in esophagus.

show abstract

Section: Resultsmentioning

confidence: 99%

A functional module-based exploration between inflammation and cancer in esophagus

Liu

Huang

et al. 2015

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…III and Stage IV COAD. Based on the assumption that the crosstalk between the stage III and stage IV COAD-related modules is significant (when the number of their interactions is significantly more than random distribution), 1000 random PPI networks were constructed (with the degree distribution of nodes in the original network remaining unchanged) [30,31]. For each pair of stage III and stage IV COAD-related modules, the real number of interactions between the module pair and the random distribution extracted from 1000 random PPI networks was compared.…”

Section: Determining Significant Crosstalk Module Pairs Of Stagementioning

confidence: 99%

Contributions of Gene Modules Regulated by Essential Noncoding RNA in Colon Adenocarcinoma Progression

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Noncoding RNAs (ncRNAs), especially microRNA (miRNA) and long noncoding RNA (lncRNA), have an impact on a variety of important biological processes during colon adenocarcinoma (COAD) progression. This includes chromatin organization, transcriptional and posttranscriptional regulation, and cell-cell signaling. The aim of this study is to identify the ncRNA-regulated modules that accompany the progression of COAD and to analyze their mechanisms, in order to screen the potential prognostic biomarkers for COAD. An integrative molecular analysis was carried out to identify the crosstalks of gene modules between different COAD stages, as well as the essential ncRNAs in the posttranscriptional regulation of these modules. 31 ncRNA regulatory modules were found to be significantly associated with overall survival in COAD patients. 17 out of the 31 modules (in which ncRNAs played essential roles) had improved the predictive ability for COAD patient survival compared to only the mRNAs of those modules, which were enriched in the core cancer hallmark pathways with closer interactions. These suggest that the ncRNAs’ regulatory modules not only exhibit close relation to COAD progression but also reflect the dynamic significant crosstalk of genes in the modules to the different malignant extent of COAD.

show abstract

“…The hypergeometric calculation, which is based on certain assumptions, has been used in systems biological analyses for determining the probability of a result occurring just by chance (73)(74)(75). The hypergeometric test can be used as a measure of over-representation and takes into account the overall population size, the number of successes within this population, the sample size, and the number of successes within the sample population.…”

Section: Specificity Filter Through Pharmacophore Model Building and mentioning

confidence: 99%

An Organic Anion Transporter 1 (OAT1)-centered Metabolic Network

Liu

Jamshidi

Chen³

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

There has been a recent interest in the broader physiological importance of multispecific "drug" transporters of the SLC and ABC transporter families. Here, a novel multi-tiered systems biology approach was used to predict metabolites and signaling molecules potentially affected by the in vivo deletion of organic anion transporter 1 (Oat1, Slc22a6, originally NKT), a major kidney-expressed drug transporter. Validation of some predictions in wetlab assays, together with re-evaluation of existing transport and knock-out metabolomics data, generated an experimentally validated, confidence ranked set of OAT1-interacting endogenous compounds enabling construction of an "OAT1-centered metabolic interaction network." Pathway and enrichment analysis indicated an important role for OAT1 in metabolism involving: the TCA cycle, tryptophan and other amino acids, fatty acids, prostaglandins, cyclic nucleotides, odorants, polyamines, and vitamins. The partly validated reconstructed network is also consistent with a major role for OAT1 in modulating metabolic and signaling pathways involving uric acid, gut microbiome products, and socalled uremic toxins accumulating in chronic kidney disease. Together, the findings are compatible with the hypothesized role of drug transporters in remote inter-organ and inter-organismal communication: The Remote Sensing and Signaling Hypothesis (Nigam, S. K. (2015) Nat. Rev. Drug Disc. 14, 29). The fact that OAT1 can affect many systemic biological pathways suggests that drug-metabolite interactions need to be considered beyond simple competition for the drug transporter itself and may explain aspects of drug-induced metabolic syndrome. Our approach should provide novel mechanistic insights into the role of OAT1 and other drug transporters implicated in metabolic diseases like gout, diabetes, and chronic kidney disease.A great deal of recent evidence suggests that solute carriers (SLC) 2 play a much broader role in physiology, including signaling and metabolism, than has been previously appreciated (1, 2). Indeed, there has been a recent call for more systematic analysis of the roles of SLCs in metabolism and signaling (1). Perhaps due to heavy emphasis on their key role in pharmacokinetics, members of the SLC (and ABC as well) "drug" transporter families are not generally depicted in biochemical pathways involving the endogenous metabolites they transport (2). Such an omission could have clinical consequences, because drugs directly or indirectly affect pathways normally involved in the movement of key metabolites, pathway intermediates, and signaling molecules, thereby fundamentally affecting cell and organ physiology in normal, pathophysiological, and developmental situations (1, 2). According to the remote sensing and signaling hypothesis, SLC and ABC drug transporters are important in regulating the movement of small endogenous molecules such as key metabolites (e.g. ␣-ketoglutarate, tryptophan metabolites), signaling molecules (e.g. cAMP, prostaglandins, polyamines), vitamins, antioxidant...

show abstract

Network Analysis Reveals Functional Cross-links between Disease and Inflammation Genes

Cited by 23 publications

References 56 publications

A functional module-based exploration between inflammation and cancer in esophagus

A functional module-based exploration between inflammation and cancer in esophagus

Contributions of Gene Modules Regulated by Essential Noncoding RNA in Colon Adenocarcinoma Progression

An Organic Anion Transporter 1 (OAT1)-centered Metabolic Network

Contact Info

Product

Resources

About