New York Regional Inborn Errors of Immunity Resource Initiative League (NY-ROYAL)

纽约地区先天性缺陷免疫资源倡议联盟 (NY-ROYAL)

基本信息

批准号：
10554965
负责人：
Dusan Bogunovic
金额：
$ 87.29万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10554965
关键词：
Affect Artificial Intelligence Back Bioinformatics Biological Biological Assay Blood specimen Bone Marrow Involvement Bone Marrow Transplantation Candidate Disease Gene Caring Classification Clinical Collaborations Consent DNA Data Databases Defect Diagnosis Diagnostic Disease Educational process of instructing Evaluation Future Genes Genetic Genetic Counseling Genetic Databases Genetic Diseases Genetic Variation Genomics Genotype Hereditary Disease High-Throughput Nucleotide Sequencing Immune System Diseases Immunity Immunologics Immunology Individual Insurance Laboratory Research Machine Learning Medicine New York Patients Phenotype Physicians Population Prevalence Price Process Production Provider Publications Recommendation Reporting Research Resources Review Committee Scientist Time Tissue Sample Triage Validation Variant Work causal variant central database clinical care clinically relevant clinically significant cohort data submission feeding functional outcomes gene discovery gene therapy genetic analysis genetic disorder diagnosis genetic variant genome sequencing multidisciplinary novel precision medicine provider portal systematic review variant of unknown significance web portal

项目摘要

Project Summary Inborn errors of immunity (IEI) are disorders of the immune system which are individually rare but collectively affect 1 in 10,000 individuals. Definitive genetic diagnosis is of essence for timely genetic counseling and clinical care. Such care may involve bone marrow transplantation, gene therapy or precision pharmacotherapeutics, all of which can be curative. The recent advancement of genome sequencing in quality and price has led to an increased rate of discovery of what are now over 400 causal genes underlying IEIs. However, about three quarters of IEI sequencing yields either variants of unknown significance (VUSs) in one of the 400+ genes or require discovery of novel causes. This leads to delays in diagnosis and treatment, especially since most of these VUSs cannot be validated using clinically available assays. As sequencing panels are increasingly utilized and being covered by insurance, the rate of genetic data production outpaces indiividuals’ capacity to interpret it. The primary purpose of this proposal is to build a regional resource which would formalize case review process, match providers and their patients carrying VUSs with research laboratories capable of targeted functional evaluation and/or bioinformatic assessment, thereby leading to VUS reclassification, diagnosis and treatment. It also will infuse research enterprises with clinically significant biological questions. We propose to streamline this process in the NY region by building a 1) patient referral platform and database where providers will be able to input deidentified patient clinical information alongside the associated genetic data (IEI gene panels, WES, and WGS sequencing), 2) a multidisciplinary review process where submitted data will be evaluated by an expert review panel at the forefront of IEI gene discovery and functional validation on a regular basis who will work to disposition relevant VUSs for 3) functional characterization by a collaborating expert team followed by 4) result reporting, VUS reclassification and its inclusion in the national clinically relevant genetic variation database. This multidisciplinary diagnostic NY regional immunology resource is key to supporting the discovery and functional characterization of novel IEI associated genetic variants. This resource will serve future, more broadly applied integration of genomics, artificial intelligence/machine learning, rapid functional assessment and precision medicine.

项目概要先天性免疫缺陷 (IEI) 是一种免疫系统疾病，个别情况很少见，但总体来说很常见影响万分之一的人，明确的基因诊断对于及时的遗传咨询和临床至关重要。此类护理可能涉及骨髓移植、基因治疗或精准药物治疗等。最近基因组测序在质量和价格方面的进步导致了治疗。目前 400 多个因果潜在基因 IEI 的发现率有所提高，但大约只有 3 个。四分之一的 IEI 测序在 400 多个基因之一中产生未知意义的变异 (VUS)，或者需要发现新的病因，这会导致诊断和治疗的延误，特别是因为大多数情况下。随着测序面板的使用越来越多，这些 VUS 无法使用临床可用的检测方法进行验证。并且在保险的覆盖下，基因数据的产生速度超过了个人的解释能力该提案的主要目的是建立一个区域资源，使案件审查正规化。流程，将携带 VUS 的提供者及其患者与能够有针对性的研究实验室相匹配功能评估和/或生物信息评估，从而导致 VUS 重新分类、诊断和我们建议，它还将给研究企业带来具有临床意义的生物学问题。通过建立 1) 患者转诊平台和数据库来简化纽约地区的这一流程提供者将能够输入未识别的患者临床信息以及相关的遗传数据（IEI 基因组、WES 和 WGS 测序），2）多学科审查过程，其中提交的数据将由 IEI 基因发现和功能验证最前沿的专家评审小组进行评估定期由合作者负责处理相关 VUS，以进行 3) 功能表征专家小组随后进行 4) 结果报告、VUS 重新分类及其纳入国家临床相关遗传变异数据库。这个多学科诊断纽约地区免疫学资源是关键支持新型 IEI 相关遗传变异的发现和功能表征。将服务于未来更广泛应用的基因组学、人工智能/机器学习、快速功能评估和精准医学。