1. Introduction1.1. RNA-based ovarian cancer research1.1.1. RNA expression profiling in ovarian cancer1.1.2. Expression profiling of microRNAs1.1.3. Ovarian cancer associated signaling pathways1.1.4. Integrative approaches in ovarian cancer research1.2. Ovarian cancer research should meet integrative multi-omics science1.2.1. Human transcriptional regulatory network1.2.2. Integration of transcriptome data with biological networks1.2.3. Differential co-expression network in ovarian cancer1.2.4. Differential interactome in ovarian cancer1.3. Ovarian diseases including polycystic ovarian syndrome (PCOS), ovarian endometriosis and ovarian cancer1.4. Aim of the Study2. Materials and Methods2.1. Reconstruction of transcriptional regulatory network of H. sapiens2.2. Topological analysis of transcriptional regulatory networks2.3. Selection of gene expression datasets2.4. Identification of differentially expressed genes2.5. Reconstruction of ovarian cancer specific subnetwork2.6. Analysis of network performance2.7. Robustness analysis2.8. Identification of reporter receptors, membrane proteins, transcription factors and miRNAs2.9. Determination of reporter metabolites2.10. Enrichment analyses of DEGs and reporter metabolites2.11. Comprehensive networks in CEPI, stroma and tumor tissues2.12. Construction of co-expression networks in diseased and healthy states2.13. Determination of network modules and their differential co-expression2.14. Prognostic power analysis of module genes2.15. Identification of transcriptional regulatory network including module genes2.16. Screening the differential expression of the module in different tumor types2.17. Differential Protein Interactome Analysis2.17.1. Protein interaction data2.17.2. Determination of entropies corresponding to each interaction3. Results and Discussion3.1. A generic transcriptional regulatory network of H. sapiens was reconstructed3.1.1. The network motifs provide a deeper investigation into the topological architecture3.1.2. Core network topology endorses the previous findings on miRNA and gene interactions3.1.3. Target genes may be regulated in cooperation of regulators3.1.4. A target gene may be regulated by multiple upstream effectors in a hierarchical operation3.1.5. Process-specific subnetworks were also dominated by hierarchical operation of regulators3.1.6. Ovarian cancer specific transcriptional regulatory network3.2. Reporter biomolecules of ovarian cancer were identified through network medicine perspective3.2.1. Transcriptomic signatures of ovarian CEPI, stroma and tumor tissues3.2.2. Signaling receivers: reporter receptors and membrane proteins3.2.3. Regulatory signatures: reporter transcription factors and microRNAs3.2.4. Metabolomic signatures: reporter metabolites3.2.5. Biological insights of transcriptomic signatures and reporter metabolites3.2.6. Tissue specific comprehensive networks with enriched reporter biomolecules3.3. Differential co-expression analysis reveals a novel prognostic gene module in ovarian cancer3.3.1. Differential gene expression in ovarian cancer3.3.2. Co-expression profiles in ovarian cancer3.3.3. Co-expressed gene modules in diseased and healthy states3.3.4. The module was differentially co-expressed in ovarian cancer3.3.5. Prognostic performance of the gene module3.3.6. Transcriptional regulators of the module genes3.3.7. Differential expression of the module genes in different tumor types3.4. Ovarian cancer differential interactome and network entropy analysis reveal new candidate biomarkers3.4.1. DNA repair responses3.4.2. Alternative splicing mechanisms and abnormal protein expression in tumor cells3.4.3. Separation of sister chromatids through ESPL13.4.4. Suppression of EGFR-associated proliferation via EGFR endocytosis and retinoids3.4.5. Nucleocytoplasmic translocation of estrogen receptor in ovarian cancer3.4.6. Cellular response to malignancies3.5. Integrative and comperative analysis of ovarian diseases point out molecular signatures3.5.1. Transcriptomic signatures: Differentially expressed genes3.5.2. Metabolic signatures: Reporter metabolites3.5.3. Regulatory signatures: Reporter TFs and miRNAs4. Conclusion5. References
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