A Multiscale Graph Theoretical Approach to Gene Regulation Networks: A Case Study in Atrial Fibrillation

Censi, Federica; Giuliani, Alessandro; Bartolini, Pietro; Calcagnini, Giovanni

doi:10.1109/tbme.2011.2150747

Cited by 37 publications

(55 citation statements)

References 11 publications

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“…This threshold also holds for super- and near-critical states; thus, as shown in Fig 2C, even a smaller ensemble of mRNAs from each critical state shows the scaling (unimodal-flattened-bimodal) to the whole expression (Fig 1). Interestingly, the same value of 50 genes as the threshold for the onset of coherent ensemble behavior was previously recognized in a completely different context and by different analytical techniques [28,29,34]. …”

Section: Resultsmentioning

confidence: 73%

Emergent Self-Organized Criticality in Gene Expression Dynamics: Temporal Development of Global Phase Transition Revealed in a Cancer Cell Line

et al. 2015

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BackgroundThe underlying mechanism of dynamic control of the genome-wide expression is a fundamental issue in bioscience. We addressed it in terms of phase transition by a systemic approach based on both density analysis and characteristics of temporal fluctuation for the time-course mRNA expression in differentiating MCF-7 breast cancer cells.MethodologyIn a recent work, we suggested criticality as an essential aspect of dynamic control of genome-wide gene expression. Criticality was evident by a unimodal-bimodal transition through flattened unimodal expression profile. The flatness on the transition suggests the existence of a critical transition at which up- and down-regulated expression is balanced. Mean field (averaging) behavior of mRNAs based on the temporal expression changes reveals a sandpile type of transition in the flattened profile. Furthermore, around the transition, a self-similar unimodal-bimodal transition of the whole expression occurs in the density profile of an ensemble of mRNA expression. These singular and scaling behaviors identify the transition as the expression phase transition driven by self-organized criticality (SOC).Principal FindingsEmergent properties of SOC through a mean field approach are revealed: i) SOC, as a form of genomic phase transition, consolidates distinct critical states of expression, ii) Coupling of coherent stochastic oscillations between critical states on different time-scales gives rise to SOC, and iii) Specific gene clusters (barcode genes) ranging in size from kbp to Mbp reveal similar SOC to genome-wide mRNA expression and ON-OFF synchronization to critical states. This suggests that the cooperative gene regulation of topological genome sub-units is mediated by the coherent phase transitions of megadomain-scaled conformations between compact and swollen chromatin states.Conclusion and SignificanceIn summary, our study provides not only a systemic method to demonstrate SOC in whole-genome expression, but also introduces novel, physically grounded concepts for a breakthrough in the study of biological regulation.

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Section: Resultsmentioning

confidence: 73%

Emergent Self-Organized Criticality in Gene Expression Dynamics: Temporal Development of Global Phase Transition Revealed in a Cancer Cell Line

et al. 2015

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“…Recently, Censi and colleagues [61] observed a significant increase in the number and strength of genes correlation under stress conditions, such as disease and environmental or physiological changes. To evaluate whether the stress induced by MMG increases the amount of correlation of the system with respect to 1 g control condition, we integrated mRNAs and miRNAs data separately for MMG and 1 g using MAGIA 2 .…”

Section: Resultsmentioning

confidence: 99%

Integration Analysis of MicroRNA and mRNA Expression Profiles in Human Peripheral Blood Lymphocytes Cultured in Modeled Microgravity

Girardi

Pittà

Casara

et al. 2014

BioMed Research International

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We analyzed miRNA and mRNA expression profiles in human peripheral blood lymphocytes (PBLs) incubated in microgravity condition, simulated by a ground-based rotating wall vessel (RWV) bioreactor. Our results show that 42 miRNAs were differentially expressed in MMG-incubated PBLs compared with 1 g incubated ones. Among these, miR-9-5p, miR-9-3p, miR-155-5p, miR-150-3p, and miR-378-3p were the most dysregulated. To improve the detection of functional miRNA-mRNA pairs, we performed gene expression profiles on the same samples assayed for miRNA profiling and we integrated miRNA and mRNA expression data. The functional classification of miRNA-correlated genes evidenced significant enrichment in the biological processes of immune/inflammatory response, signal transduction, regulation of response to stress, regulation of programmed cell death, and regulation of cell proliferation. We identified the correlation of miR-9-3p, miR-155-5p, miR-150-3p, and miR-378-3p expression with that of genes involved in immune/inflammatory response (e.g., IFNG and IL17F), apoptosis (e.g., PDCD4 and PTEN), and cell proliferation (e.g., NKX3-1 and GADD45A). Experimental assays of cell viability and apoptosis induction validated the results obtained by bioinformatics analyses demonstrating that in human PBLs the exposure to reduced gravitational force increases the frequency of apoptosis and decreases cell proliferation.

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“…The gene selection method and the thresholding approach were previously used on a different case [19]. The genes with highest absolute scores on the discriminant component are the ones whose relative concentration is mostly influenced by the "regulation pattern" correspondent to the component itself, consequently the study of the mutual correlations among these genes carried out separately in control and patient data set is expected to give important hints on the pathological mechanisms of the studied disease [20].…”

Section: Discussionmentioning

confidence: 99%

Gene Regulation Networks in Early Phase of Duchenne Muscular Dystrophy

Bernardini

Censi

Lattanzi

et al. 2013

IEEE/ACM Trans. Comput. Biol. and Bioinf.

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The aim of this study was to analyze previously published gene expression data of skeletal muscle biopsies of Duchenne muscular dystrophy (DMD) patients and controls (gene expression omnibus database, accession #GSE6011) using systems biology approaches. We applied an unsupervised method to discriminate patient and control populations, based on principal component analysis, using the gene expressions as units and patients as variables. The genes having the highest absolute scores in the discrimination between the groups, were then analyzed in terms of gene expression networks, on the basis of their mutual correlation in the two groups. The correlation network structures suggest two different modes of gene regulation in the two groups, reminiscent of important aspects of DMD pathogenesis.

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A Multiscale Graph Theoretical Approach to Gene Regulation Networks: A Case Study in Atrial Fibrillation

Cited by 37 publications

References 11 publications

Emergent Self-Organized Criticality in Gene Expression Dynamics: Temporal Development of Global Phase Transition Revealed in a Cancer Cell Line

Emergent Self-Organized Criticality in Gene Expression Dynamics: Temporal Development of Global Phase Transition Revealed in a Cancer Cell Line

Integration Analysis of MicroRNA and mRNA Expression Profiles in Human Peripheral Blood Lymphocytes Cultured in Modeled Microgravity

Gene Regulation Networks in Early Phase of Duchenne Muscular Dystrophy

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