Preclinical exploration of the DNA damage response pathway using the interactive neuroblastoma cell line explorer CLEAN.

IF 3.4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY NAR cancer Pub Date : 2024-01-11 eCollection Date: 2024-03-01 DOI:10.1093/narcan/zcad062
Jonatan L Gabre, Peter Merseburger, Arne Claeys, Joachim Siaw, Sarah-Lee Bekaert, Frank Speleman, Bengt Hallberg, Ruth H Palmer, Jimmy Van den Eynden
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Abstract

Neuroblastoma (NB) is the most common cancer in infancy with an urgent need for more efficient targeted therapies. The development of novel (combinatorial) treatment strategies relies on extensive explorations of signaling perturbations in neuroblastoma cell lines, using RNA-Seq or other high throughput technologies (e.g. phosphoproteomics). This typically requires dedicated bioinformatics support, which is not always available. Additionally, while data from published studies are highly valuable and raw data (e.g. fastq files) are nowadays released in public repositories, data processing is time-consuming and again difficult without bioinformatics support. To facilitate NB research, more user-friendly and immediately accessible platforms are needed to explore newly generated as well as existing high throughput data. To make this possible, we developed an interactive data centralization and visualization web application, called CLEAN (the Cell Line Explorer web Application of Neuroblastoma data; https://ccgg.ugent.be/shiny/clean/). By focusing on the regulation of the DNA damage response, a therapeutic target of major interest in neuroblastoma, we demonstrate how CLEAN can be used to gain novel mechanistic insights and identify putative drug targets in neuroblastoma.

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利用交互式神经母细胞瘤细胞系探索器 CLEAN 对 DNA 损伤反应途径进行临床前探索。
神经母细胞瘤(NB)是婴儿期最常见的癌症,迫切需要更有效的靶向疗法。新型(组合)治疗策略的开发有赖于利用 RNA-Seq 或其他高通量技术(如磷蛋白组学)对神经母细胞瘤细胞系中的信号扰动进行广泛探索。这通常需要专门的生物信息学支持,但并非总能获得。此外,虽然已发表的研究数据非常有价值,而且原始数据(如 fastq 文件)如今已在公共资料库中发布,但数据处理非常耗时,而且没有生物信息学支持也很困难。为了促进 NB 研究,需要有更多用户友好、可立即访问的平台来探索新生成的和现有的高通量数据。为此,我们开发了一个交互式数据集中和可视化网络应用程序,名为 CLEAN(神经母细胞瘤数据的细胞系资源管理器网络应用程序;https://ccgg.ugent.be/shiny/clean/)。DNA 损伤反应是神经母细胞瘤的主要治疗靶点,通过重点研究 DNA 损伤反应的调控,我们展示了如何利用 CLEAN 获得新的机理认识并确定神经母细胞瘤的潜在药物靶点。
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