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.

未诊断的疾病和罕见疾病不尊重年龄，地理，社会经济地位或教育水平。他们很难科学地定义并进行分类，但罕见的疾病影响了美国的3000万人，而未诊断的疾病尚未达到尚未受到影响。转介到Chop/Upenn UDN不仅反映了一个更大的集水区域，而不仅仅是四州地理区域，而且反映了未诊断和罕见疾病患者人群的固有二分法。我们的UDN计划采用了一种成熟的协作方法来满足未持居民的人群的需求，我们被毒死通过改进的工作流程和计算方法而中毒。该申请提出三个旨在为我们的原始分配期望以外的其他患者提供服务。 AIM 1描述了我们将在入学和评估工作流程中实施的整体诊断方法和更改。在AIM 2中，我们描述了新的诊断策略，重点是改善生物信息学。在AIM 3中，我们描述了我们的长期可持续性计划，并过渡到这一新模型。我们一直在临床和转化研究中心看到患者，该中心被称为人类现象科学中心（CHP），该中心拥有标准化方法，我们开发了一个模板以更狭窄的数据捕获，以更轻松地定义关键表型。新设想的工作流程结合了一种分层的诊断方法。患者将进行下一代测序，代谢组学和/或免疫学测试，并认为可以轻松地以这种方式进行某些诊断，从而简化患者体验。那些尚未解决的人将具有深层的表型和多摩学的诊断方法。我们的临床站点具有宝贵的专业知识，并在近四分之一的患者中成功实现了诊断。我们当前的UDN实践为我们的未来模型提供了很大的了解，并将结合简化基因组分析方法的机会，并与我们机构的持续努力接触，以将“ OMICS”的心态更全面地纳入诊断之旅。我们的可持续性模型还将改善多样性，共享技术基础架构和计算方法，加速外展和传播方法，并与研究界的变体和基因验证更广泛地接口。我们拥有机构资金的希望，并有毒以发展我们的计划，以适应更多的患者，改善人口多样性，改善患者的诊断多样性，并使用UDN模型来提高诊断技术方法的临床水平。