Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
BMC Gastroenterol. 2021 Sep 25;21(1):353. doi: 10.1186/s12876-021-01930-2.
Primary sclerosing cholangitis (PSC) is a rare, chronic cholestatic liver disease that often progresses to end-stage liver disease and/or the development of hepatobiliary neoplasia. Lack of prognostic tools and treatment options for PSC is driven in part by our poor understanding of its pathogenesis, which is thought to be complex, the interaction of genetic variants, environmental influences and biological response throughout the course of disease. The PSC Scientific Community Resource (PSC-SCR) seeks to overcome previous shortcomings by facilitating novel research in PSC with the ultimate goals of individualizing patient care and improving patient outcomes.
PSC patients who receive their health care at Mayo Clinic or a collaborating site are identified by chart review and invited in person or by mail to participate. Non-Mayo patients are offered enrollment if they provide sufficient access to their medical records to evaluate inclusion/exclusion criteria. Controls without liver disease are identified with assistance of the Mayo Clinic Biobank. Participant consent is obtained at the beginning of the recruitment process by mail-in, electronic or face-to-face protocols. Clinical data is extracted from the medical record by qualified physicians and entered in a custom designed database. Participants fill out a custom-designed, comprehensive questionnaire, which collects scientifically relevant demographic and clinical information. Biospecimens are collected using mail-in kits thar are returned via overnight carrier service and processed by the biospecimen accessioning and processing facility at Mayo Clinic, which coordinates sample transfers and provides required sample preparation services. The resource is currently being utilized to perform omics-scale projects investigating the exposome, metabolome, methylome, immunome and microbiome in PSC. Datasets and residual biospecimens will be shared with researchers proposing scientifically sound PSC-focused research with approval of the appropriate review boards.
Patient-based studies leveraging the latest technologies for targeted and wide-scale interrogation of multiple omics layers offer promise to accelerate PSC research through discovery of unappreciated aspects of disease pathogenesis. However, the rarity of PSC severely limits such studies. Here we describe our effort to overcome this limitation, the PSC-SCR, a repository of patient biospecimens coupled with clinical and omics data for use by the broader PSC research community.
原发性硬化性胆管炎（PSC）是一种罕见的慢性胆汁淤积性肝病，常进展为终末期肝病和/或肝胆肿瘤的发生。缺乏针对 PSC 的预后工具和治疗选择部分归因于我们对其发病机制的理解不足，该机制被认为是复杂的，涉及遗传变异、环境影响和疾病过程中的生物反应的相互作用。PSC 科学社区资源（PSC-SCR）旨在通过促进 PSC 的新研究来克服以前的不足，最终目标是实现患者护理的个体化和改善患者的预后。
通过病历审查确定在梅奥诊所或合作机构接受治疗的 PSC 患者，并通过亲自或邮寄邀请他们参与。如果非梅奥诊所患者能够提供足够的访问其病历的权限来评估纳入/排除标准，则为他们提供入组机会。通过梅奥诊所生物库确定无肝脏疾病的对照者。在招募过程开始时，通过邮寄、电子或面对面的协议获得参与者的同意。合格的医生从病历中提取临床数据并输入到定制的数据库中。参与者填写一份定制的综合问卷，收集与科学相关的人口统计学和临床信息。使用邮寄试剂盒收集生物样本，这些试剂盒通过隔夜快递服务退回，并由梅奥诊所的生物样本采集和处理设施处理，该设施协调样本转移并提供所需的样本制备服务。该资源目前正被用于进行基于组学的项目，以研究 PSC 中的外显子组、代谢组、甲基组、免疫组和微生物组。数据集和剩余的生物样本将与提出具有科学依据的、以 PSC 为重点的研究的研究人员共享，前提是获得适当的审查委员会的批准。
利用最新技术针对多个组学层面进行靶向和广泛检测的基于患者的研究有望通过发现疾病发病机制中未被认识到的方面来加速 PSC 研究。然而，PSC 的罕见性严重限制了此类研究。在这里，我们描述了我们克服这一限制的努力，PSC-SCR，这是一个患者生物样本库，与临床和组学数据相结合，供更广泛的 PSC 研究社区使用。
