一个适用于整合基因组尺度代谢模型以提高洞察力的反应性物种反应模块：癌症应用研究。
A reactive species reactions module for integration into genome-scale metabolic models for improved insights: Application to cancer.
发表日期：2023 Sep 07
作者：
Subasree Sridhar, Prerna Bhalla, Justin Kullu, Sriya Veerapaneni, Swagatika Sahoo, Nirav Bhatt, G K Suraishkumar
来源：
Disease Models & Mechanisms
摘要：
反应性物质（RS）在许多疾病背景下起到重要作用。尽管RS在包括癌症在内的疾病中发挥关键作用，但在基因组规模代谢（GSM）模型中对其进行的建模不足，而这些模型用于理解疾病背景下的细胞代谢。我们开发了可扩展的RS反应模块，可以与任何Recon 3D导出的人类代谢模型集成，或经过细调后，与任何代谢模型集成。通过RS集成，从Recon 3D构建的三种癌症（基底样三阴性乳腺癌（TNBC）、高级别浆液性卵巢癌（HGSOC）和结直肠癌（CRC））的GSM模型明确突出了这些癌症重要途径中的通量（失衡）的增加/减少。在没有RS模块的标准癌症模型中，这些失调并不明显。此外，这些RS集成癌症GSM模型的结果表明，治疗这些癌症靶向铁死亡的易受性从高到低依次为：TNBC > HGSOC > CRC。版权所有 © 2023. Elsevier Inc.出版。
Reactive species (RS) play significant roles in many disease contexts. Despite their crucial roles in diseases including cancer, the RS are not adequately modeled in the genome-scale metabolic (GSM) models, which are used to understand cell metabolism in disease contexts. We have developed a scalable RS reactions module that can be integrated with any Recon 3D-derived human metabolic model, or after fine-tuning, with any metabolic model. With RS-integration, the GSM models of three cancers (basal-like triple negative breast cancer (TNBC), high grade serous ovarian carcinoma (HGSOC) and colorectal cancer (CRC)) built from Recon 3D, precisely highlighted the increases/decreases in fluxes (dysregulation) occurring in important pathways of these cancers. These dysregulations were not prominent in the standard cancer models without the RS module. Further, the results from these RS-integrated cancer GSM models suggest the following decreasing order in the ease of ferroptosis-targeting to treat the cancers: TNBC > HGSOC > CRC.Copyright © 2023. Published by Elsevier Inc.