title: Multiple Differential Networks Strategy Reveals Carboplatin and Melphalan-Induced Dynamic Module Changes in Retinoblastoma.
abstract: BACKGROUND Retinoblastoma (RB) is the most common malignant tumor of the eye in childhood. The objective of this paper was to investigate carboplatin (CAR)- and melphalan (MEL)-induced dynamic module changes in RB based on multiple (M) differential networks, and to generate systems-level insights into RB progression. MATERIAL AND METHODS To achieve this goal, we constructed M-differential co-expression networks (DCNs), assigned a weight to each edge, and identified seed genes in M DCNs by ranking genes based on their topological features. Starting with seed genes, a module search was performed to explore candidate modules in CAR and MEL condition. M-DMs were detected according to significance evaluations of M-modules, which originated from refinement of candidate modules. Further, we revealed dynamic changes in M-DM activity and connectivity on the basis of significance of Module Connectivity Dynamic Score (MCDS). RESULTS In the present study, M=2, a total of 21 seed genes were obtained. By assessing module search, refinement, and evaluation, we gained 18 2-DMs. Moreover, 3 significant 2-DMs (Module 1, Module 2, and Module 3) with dynamic changes across CAR and MEL condition were determined, and we denoted them as dynamic modules. Module 1 had 27 nodes of which 6 were seed genes and 56 edges. Module 2 was composed of 28 nodes and 54 edges. A total of 28 nodes interacted with 45 edges presented in Module 3. CONCLUSIONS We have identified 3 dynamic modules with changes induced by CAR and MEL in RB, which might give insights in revealing molecular mechanism for RB therapy.
authors.affiliation: Department of Ophthalmology, Yidu Central Hospital of Weifang, Qingzhou, Shandong, China (mainland).
authors.forename: Cui
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Yidu Central Hospital of Weifang, Qingzhou, Shandong, China (mainland).
authors.forename: Feng-Wei
authors.initials: FW
authors.lastname: Ma
authors.affiliation: Department of Ophthalmology, Yidu Central Hospital of Weifang, Qingzhou, Shandong, China (mainland).
authors.forename: Cui-Yun
authors.initials: CY
authors.lastname: Du
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China (mainland).
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D016190:Carboplatin / Q000494:pharmacology / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D008558:Melphalan / Q000494:pharmacology / Q000627:therapeutic use*; D012175:Retinoblastoma / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D016190:Carboplatin; D008558:Melphalan