Scripps Clinic Bio-Repository and Bio-Informatics Core.
Scripps Center for Organ Transplantation, La Jolla.
Curr Opin Organ Transplant. 2021 Feb 1;26(1):37-42. doi: 10.1097/MOT.0000000000000837.
Organ transplantation research has led to the discovery of several interesting individual mechanistic pathways, molecules and potential drug targets but there are still no comprehensive studies that have addressed how these varied mechanisms work in unison to regulate the posttransplant immune response that drives kidney rejection and dysfunction.
Systems biology is a rapidly expanding field that aims to integrate existing knowledge of molecular concepts and large-scale genomic and clinical datasets into networks that can be used in cutting edge computational models to define disease mechanisms in a holistic manner. Systems biology approaches have brought a paradigm shift from a reductionist view of biology to a wider agnostic assessment of disease from several lines of evidence. Although the complex nature of the posttransplant immune response makes it difficult to pinpoint mechanisms, systems biology is enabling discovery of unknown biological interactions using the cumulative power of genomic data sets, clinical data and endpoints, and improved computational methods for the systematic deconvolution of this response.
An integrative systems biology approach that leverages genomic data from varied technologies, such as DNA sequencing, copy number variation, RNA sequencing, and methylation profiles along with long-term clinical follow-up data has the potential to define a framework that can be mined to provide novel insights for developing therapeutic interventions in organ transplantation.
器官移植研究发现了一些有趣的个体机制途径、分子和潜在的药物靶点,但仍没有全面的研究来解决这些不同的机制如何协同作用,调节导致肾移植排斥和功能障碍的移植后免疫反应。
系统生物学是一个快速发展的领域,旨在将分子概念的现有知识和大规模基因组及临床数据集整合到网络中,这些网络可用于前沿的计算模型,全面定义疾病机制。系统生物学方法带来了从生物学还原论观点到从多个证据来源对疾病进行更广泛的不可知评估的范式转变。尽管移植后免疫反应的复杂性使得难以确定机制,但系统生物学正在利用基因组数据集、临床数据和终点的累积力量,以及用于系统解析该反应的改进计算方法,发现未知的生物学相互作用。
利用来自多种技术的基因组数据(如 DNA 测序、拷贝数变异、RNA 测序和甲基化谱)以及长期临床随访数据的综合系统生物学方法,有可能定义一个可以挖掘的框架,为开发器官移植治疗干预措施提供新的见解。