UDN@CHOP/UPENN: transition to sustainability

UDN@CHOP/UPENN：向可持续发展过渡

基本信息

批准号：
10905924
负责人：
Daniel James Rader
金额：
$ 35.6万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-20 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10905924
关键词：
Acceleration Address Affect Age Attention Automation Bioinformatics Caring Catchment Area Center for Translational Science Activities Classification Clinical Research Collaborations Communication Communities Computing Methodologies Data Data Analyses Data Collection Developmental Delay Disorders Diagnosis Diagnostic Diagnostic Services Diagnostics Research Dimensions Disease Education Education and Outreach Educational Status Enrollment Equity Evaluation Frustration Funding Future Genes Genomics Geographic Locations Geographic state Geography Goals Human Immunological Diagnosis Immunologics Immunology Infrastructure Institution Knowledge Manuscripts Medical Metabolic Modeling Names Pathway interactions Patients Persons Phenotype Philadelphia Physical Examination Physicians Positioning Attribute Preparation Process Program Sustainability Rare Diseases Research Sampling Science Site Socioeconomic Status Standardization System Technology Telemedicine Testing Time Training U-Series Cooperative Agreements Underserved Population Validation Variant Visit analytical method bioinformatics pipeline clinical research site collaborative approach diagnostic strategy empowerment exome sequencing expectation experience genetic disorder diagnosis genome sequencing improved innovation member metabolomics multiple omics next generation sequencing novel diagnostics outreach patient outreach patient population phenomics programs research clinical testing sample collection skills success timeline transcriptome sequencing underserved community whole genome

项目摘要

Undiagnosed diseases and rare diseases occur without respect to age, geography, socioeconomic status or level of education. They are frustratingly hard to define scientifically and to classify, yet rare diseases affect 30 million people in the USA and the undiagnosed are as yet uncounted. Referrals to the CHOP/UPENN UDN reflect a larger catchment area than just the four-state geographical region and reflect the inherent dichotomy of the undiagnosed and rare disease patient populations. Our UDN program has a mature collaborative approach to address the needs of the undiagnosed patient population and we are poised to grow through improved workflows and computational approaches. This application proposes three Aims to serve additional patients beyond the expectation of our original allocation. Aim 1 describes our overall diagnostic approach and changes we will implement in enrollment and evaluation workflows. In Aim 2, we describe new diagnostic strategies, focusing on improved bioinformatics. In Aim 3, we describe our long term sustainability plans and transition to this new model. We have been seeing patients in the Clinical and Translational Research Center, named Center for Human Phenomic Science (CHPS), which facilitates a standardized approach and we have developed a template for a narrow data capture to more easily define the key phenotypes. The newly envisioned workflow incorporates a tiered approach to diagnostics. Patients will have next generation sequencing, metabolomics, and/or immunology testing prior to being seen, reasoning that some diagnoses can be easily made in this way and thus streamlining the patient experience. Those that remain unsolved will have deep phenotyping and a multi-omics approach to diagnosis. Our Clinical Site has valuable expertise and has been successful in achieving diagnosis for nearly a quarter of the patients. Our future model is informed heavily by our current UDN practices and will additionally incorporate opportunities to streamline genomic analytic methods, interfacing with ongoing efforts at our institutions to incorporate the “omics” mindset more fully into the diagnostic journey. Our sustainability model will also improve diversity, sharing technology infrastructure and computational methods, accelerating outreach and dissemination approaches, and interfacing more widely with the research community for variant and gene validation. We have the promise of institutional funds and are poised to grow our program to accommodate more patients, improve the demographic diversity, improve the patient diagnostic diversity, and use the UDN model to improve clinician proficiancy with technologic approaches to diagnosis.

未确诊的疾病和罕见疾病的发生与年龄、地理位置、社会经济地位或教育水平无关，令人沮丧的是，罕见疾病影响着美国 3000 万人，而未确诊的疾病尚未被统计。 CHOP/UPENN UDN 反映了比四个州地理区域更大的服务范围，并反映了未确诊和罕见疾病患者群体的固有二分性。我们的 UDN 计划拥有成熟的计划。该应用程序提出了三个目标，以服务超出我们最初分配预期的更多患者。目标 1 描述了我们的总体诊断方法和变化。我们将在目标 2 中实施新的诊断策略，重点关注改进的生物信息学。在目标 3 中，我们描述了我们的长期可持续发展计划以及向这种新模式的过渡。临床和转化研究中心，名为人类表型科学中心（CHPS），它促进了标准化方法，我们开发了一个用于窄数据捕获的模板，以更轻松地定义关键表型。新设想的工作流程采用了分层方法。患者在就诊之前将进行下一代测序、代谢组学和/或免疫学测试，认为通过这种方式可以轻松做出一些诊断，从而简化患者的体验。我们的临床站点拥有宝贵的专业知识，并已成功地为近四分之一的患者实现了诊断。我们未来的模型在很大程度上借鉴了我们当前的 UDN 实践，并将另外纳入简化基因组的机会。分析方法，与我们机构正在进行的努力相结合，将“组学”思维更充分地融入到诊断过程中，我们的可持续发展模型也将提高多样性，共享技术基础设施和计算方法，加速外展和传播方法，并与更广泛的领域进行联系。研究团体我们有机构资金的承诺，并准备扩大我们的计划以容纳更多患者，改善人口多样性，改善患者诊断多样性，并使用 UDN 模型提高临床医生诊断技术方法的熟练程度。