Biostatistics and Systems Medicine Core Unit (Z2-Project)

生物统计学和系统医学核心单元（Z2项目）

• 批准号: 279215450
• 负责人: Professor Dr. Hauke Busch
• 金额: --
• 依托单位: Klinik für Dermatologie, Allergologie und Venerologie (Hautklinik)
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/279215450?language=en
• 关键词: Biostatistics; Systems; Medicine; Core; Unit

State-of-the-art biostatistics and systems medicine has revolutionized the research on most complex and heterogeneous diseases. Thus, the in-depth biomathematical analysis of individual datasets and the integration of multi-dimensional datasets has enabled defining molecular networks and their significance for the pathogenesis of disease in an unbiased manner and to a degree not achievable by classical biomedical research approaches. While these approaches are now frequently applied on common diseases, such as cardiovascular disorders, and have become the driver to evolve patient care towards the precision medicine level, their application in less common diseases, including pemphigoid diseases (PDs), is still in its infancy. However, especially in these diseases with a naturally low sample size, sophisticated biomathematical/systems medicine approaches exploiting, extrapolating, and integrating all datasets available on individual patients are key to further illuminate these diseases in a cost-effective manner. To exploit these new possibilities for PDs and to ensure the most comprehensive analysis and scientific exploitation of all datasets generated in the CRU, the core unit Biostatistics & Systems Medicine (Z2-Project) was established in the 1st FP. In the 2nd FP, the Z2-Project will continue these services. Among others, it will conduct basic and mechanistic epidemiological studies and deep phenotyping of PD patients to define patient subgroups, thus uncovering the pathogenesis of PDs and contributing to the development of personalized treatment regimens. It will also identify gene variants and molecular pathways regulating PDs. In addition, it will, e.g., resolve the interactions between both the nuclear and mitochondrial genomes with the skin microbiota and their impact on PD. It will also perform a trans-ome-wide association study (transOWAS) integrating the datasets on multiple omics layers generated in the CRU with each other and with the phenomes of BP patients to establish cause-effect relationships between pathway and disease activity. This will be instrumental to identify the most promising therapeutic targets and to develop new multi-variate biomarkers for PDs. The significance of both will be subsequently experimentally/clinically addressed in the CRU projects. Conversely, the Z2-Project will also integrate experimental results from preclinical models into models to identify common subnets of PD in mice and men and their pathogenic role. Thus, collectively, the Z2-Project will be the brain of the CRU. It will be pivotal for the translation of the results of the CRU into the human situation and to elucidate the pathogenesis of PD in the ultimate model system, the patient. It will be key to finally achieve its overall aim, the establishment of a comprehensive model of the molecular processes orchestrating the effector phase of PDs, and the development of therapeutic interventions selectively interfering with these processes.

最先进的生物统计学和系统医学已经彻底改变了大多数复杂和异质性疾病的研究。因此，对单个数据集的深入生物数学分析和多维数据集的整合使得以公正的方式定义分子网络及其对疾病发病机制的意义成为可能，并且在一定程度上是经典生物医学研究方法无法实现的。虽然这些方法现在经常应用于常见疾病，如心血管疾病，并已成为推动患者护理向精准医疗水平发展的动力，但它们在不太常见的疾病，包括类天疱疮疾病（pd）中的应用仍处于起步阶段。然而，特别是在这些自然低样本量的疾病中，复杂的生物数学/系统医学方法利用、外推和整合所有可用的个体患者数据集是以具有成本效益的方式进一步阐明这些疾病的关键。为了开发pd的这些新可能性，并确保对CRU生成的所有数据集进行最全面的分析和科学利用，生物统计学和系统医学（z2项目）的核心单元在第一计划中成立。在第二个FP中，Z2-Project将继续这些服务。其中，开展基础和机制流行病学研究，对PD患者进行深度表型分析，确定患者亚群，从而揭示PD的发病机制，促进个性化治疗方案的制定。它还将确定调节pd的基因变异和分子途径。此外，它还将解决核基因组和线粒体基因组与皮肤微生物群之间的相互作用及其对PD的影响。该研究还将开展跨基因组关联研究（trans-ome-wide association study, transsowas），将CRU中生成的多个组学层的数据集相互整合，并与BP患者的现象相结合，建立通路与疾病活动性之间的因果关系。这将有助于确定最有希望的治疗靶点，并为pd开发新的多变量生物标志物。这两者的重要性将随后在CRU项目中进行实验/临床研究。相反，Z2-Project还将把临床前模型的实验结果整合到模型中，以确定小鼠和男性PD的常见子网及其致病作用。因此，总的来说，z2项目将是CRU的大脑。这对于将CRU的结果转化为人类情况以及阐明PD在最终模型系统（患者）中的发病机制至关重要。这将是最终实现其总体目标的关键，建立一个协调pd效应阶段的分子过程的综合模型，并开发有选择地干扰这些过程的治疗干预措施。