Local and Systemic Multi-Omics of TMJ Disorders

颞下颌关节疾病的局部和系统多组学

• 批准号: 10524689
• 负责人: Sharon Aronovich
• 金额: $ 42.02万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-09 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10524689
• 关键词: Age; Arthralgia; Biological; Biological Assay; Biological Markers; Biology; Blood specimen; Calibration; Categories; Cells; Classification; Clinical; Clinical Research; Collection; Complex; Computational Biology; Country; DNA Methylation; Data; Degenerative Disorder; Degenerative polyarthritis; Diagnostic; Disease; Disease Progression; Dissection; Fibromyalgia; Foundations; Functional disorder; Goals; Headache; Health Care Costs; Image; Individual; Joints; Knowledge; Machine Learning; Manuals; Methods; Molecular; Molecular Profiling; Multiomic Data; Musculoskeletal Diseases; Operative Surgical Procedures; Pain; Pathologic; Pathway interactions; Patient Recruitments; Patients; Phase; Phenotype; Pilot Projects; Population; Precision therapeutics; Prevention; Procedures; Productivity; Protocols documentation; Quality of life; RNA methylation; Reproducibility; Research Design; Research Personnel; Retrieval; Saliva; Salivary; Sampling; Services; Severities; Severity of illness; Site; Standardization; Symptoms; Synovial Cell; Synovial Fluid; System; Temporomandibular Joint; Temporomandibular Joint Disorders; Testing; Therapeutic; Tissues; Translational Research; Woman; Work; base; case control; clinical phenotype; cohort; comorbidity; data integration; data management; data standards; design; disease phenotype; disorder subtype; epigenomics; healthy volunteer; indexing; insight; multiple omics; novel; palliative; patient stratification; precision medicine; prognostic; proteomic signature; quality assurance; recruit; reproductive; response; sample collection; sound; success; transcriptomics

Project Summary/Abstract Temporomandibular Disorders (TMD) represent a spectrum of painful disorders that afflicts approximately 5 to 10% of the US population with approximate annual healthcare costs of $4 billion. Degenerative disorders, internal derangements including disc displacement and hypo/hyper-mobility, and arthralgia of the temporomandibular joint (TMJ), which together are referred to as TMJ disorders (TMJDs), are common in many subjects with TMD. No definitive etio-pathologic diagnostics are currently available, and treatments are non-specific and largely palliative. While a subset of TMJDs occur in isolation, a substantial proportion are associated with comorbidities such as headaches and/or fibromyalgia. These two distinct patient cohorts together with the peculiar predilection of TMJDs for women of reproductive age as opposed to the late onset of similar disorders in other joints, point to unique and complex interactions of systemic and local factors. As such, multi-omic signatures and cell networks at the local and systemic levels will facilitate specific diagnostics and clinically meaningful stratification of patients between and within each of these cohorts. Currently there is a substantial void in connecting the molecular multi-omic signatures and cellular networks / interactions with clinical disease subtypes, etiopathogenesis, progression and severity. Our long-term goal is to identify local and systemic single cell and biofluid multi-omic molecular profiles from a spectrum of TMJD subtypes and severities to delineate relationships between clinical phenotypes with deep omic signatures and cell networks that will nucleate new directions for rational and precision therapies, prognostics and prevention. We expect that such multi-omic analyses combined with case control and longitudinal clinical and imaging data will provide critical insights on novel molecular signatures and networks associated with specific disease subtypes / severity and the interactions between cell subpopulations in perpetuating or mitigating disease progression. These goals will be achieved through two milestones-based phases involving (1) a UH2 feasibility phase to develop and implement protocols and quality assurance; recruitment of subjects and clinical disease categorization; sample collection to pilot sample handling and omic assays; data standardization, management and access; and developing a robust statistical plan; and (2) a UH3 implementation and discovery phase to identify distinct cell networks and molecular signatures towards a new rational classification of TMJDs and comorbidities; and to validate salivary omics biomarkers of these endotypes. Given the assembled expertise and plans, we expect that these studies will provide strong foundations and depth of knowledge needed to more rationally stratify patients into TMJD and comorbidity subtypes and severity categories; provide the basis for new directions of translational science in diagnostics, prognostics and therapeutics based on multi-omics of individual disease subtypes and the implementation of precision medicine for these patients; and define homeostatic and disease signatures that are specific to the TMJ as opposed to appendicular joints.

项目摘要/摘要 颞下颌关节紊乱症(TMD)代表一系列痛苦的疾病，大约5到5岁 占美国人口的10%，每年的医疗费用约为40亿美元。退行性疾病， 关节盘内紊乱，包括关节盘移位和低/高活动度，以及关节痛 颞下颌关节(TMJ)，统称为TMJ障碍(TMJD)，在 许多受试者患有TMD。目前还没有明确的病因病理诊断方法，治疗方法是 不明确，基本上是姑息治疗。虽然TMJD的子集单独出现，但相当大的比例是 与头痛和/或纤维肌痛等合并症有关。这两组截然不同的患者 再加上TMJDS对育龄妇女的特殊偏好，而不是晚发性 其他关节的类似疾病，表明全身和局部因素的独特和复杂的相互作用。AS 这种在局部和系统层面上的多组特征和细胞网络将有助于特定的诊断 在这些队列之间和队列内对患者进行有临床意义的分层。目前有一个 在连接分子多组体签名和细胞网络/相互作用方面存在实质性空白 临床疾病亚型、病因、进展和严重程度。我们的长期目标是确定当地的 以及来自TMJD亚型和TMJD亚型谱的系统性单细胞和生物体液多组分子图谱 描述具有深层基因组特征的临床表型和细胞网络之间关系的严肃性 这将为合理和精确的治疗、预测和预防提供新的方向。我们预计 这种多组学分析结合病例对照和纵向临床和影像数据将 提供有关与特定疾病亚型相关的新分子特征和网络的重要见解 /严重性和细胞亚群之间在持久或减缓疾病进展中的相互作用。 这些目标将通过两个基于里程碑的阶段来实现，其中包括(1)UH2可行性阶段，以 制定和实施方案和质量保证；招募受试者和临床疾病 分类.用于试行样品处理和基因组分析的样品采集.数据标准化和管理 以及(2)UH3实施和发现阶段，以 识别不同的细胞网络和分子特征，以实现对TMJD和TMJD的新的合理分类 并验证这些内型的唾液组学生物标志物。考虑到集合的专业知识 和计划，我们期望这些研究将提供所需的坚实基础和知识深度 更合理地将患者分成TMJD和共病亚型和严重程度类别；提供依据 关于基于多组学的诊断、预后和治疗学的翻译科学的新方向 个别疾病亚型和对这些患者实施精准医学的情况；以及界定 动态平衡和疾病征象是TMJ特有的，而不是附件关节。