Precision diagnostics in transplanted organs using microarray-assessed gene expression: concepts and technical methods of the Molecular Microscope® Diagnostic System (MMDx).

IF 6.7 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Katelynn S Madill-Thomsen, Philip F Halloran
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引用次数: 0

Abstract

There is a major unmet need for improved accuracy and precision in the assessment of transplant rejection and tissue injury. Diagnoses relying on histologic and visual assessments demonstrate significant variation between expert observers (as represented by low kappa values) and have limited ability to assess many biological processes that produce little histologic changes, for example, acute injury. Consensus rules and guidelines for histologic diagnosis are useful but may have errors. Risks of over- or under-treatment can be serious: many therapies for transplant rejection or primary diseases are expensive and carry risk for significant adverse effects. Improved diagnostic methods could alleviate healthcare costs by reducing treatment errors, increase treatment efficacy, and serve as useful endpoints for clinical trials of new agents that can improve outcomes. Molecular diagnostic assessments using microarrays combined with machine learning algorithms for interpretation have shown promise for increasing diagnostic precision via probabilistic assessments, recalibrating standard of care diagnostic methods, clarifying ambiguous cases, and identifying potentially missed cases of rejection. This review describes the development and application of the Molecular Microscope® Diagnostic System (MMDx), and discusses the history and reasoning behind many common methods, statistical practices, and computational decisions employed to ensure that MMDx scores are as accurate and precise as possible. MMDx provides insights on disease processes and highly reproducible results from a comparatively small amount of tissue and constitutes a general approach that is useful in many areas of medicine, including kidney, heart, lung, and liver transplants, with the possibility of extrapolating lessons for understanding native organ disease states.

利用芯片评估基因表达对移植器官进行精确诊断:分子显微镜®诊断系统(MMDx)的概念和技术方法。
在评估移植排斥反应和组织损伤方面,提高准确性和精确度是一项尚未得到满足的重大需求。依赖组织学和肉眼评估的诊断结果显示,专家观察者之间的差异很大(表现为较低的卡帕值),而且对许多几乎不产生组织学变化的生物过程(如急性损伤)的评估能力有限。组织学诊断的共识规则和指南很有用,但也可能存在误差。过度治疗或治疗不足的风险可能很严重:许多治疗移植排斥或原发性疾病的疗法都很昂贵,而且有可能产生严重的不良反应。改进诊断方法可以减少治疗误差,提高疗效,并作为新药临床试验的有用终点,从而改善治疗效果,从而降低医疗成本。使用微阵列进行分子诊断评估,结合机器学习算法进行解释,有望通过概率评估提高诊断精确度,重新校准标准护理诊断方法,澄清模糊病例,并识别可能遗漏的排斥病例。本综述介绍了分子显微镜® 诊断系统(MMDx)的开发和应用,并讨论了许多常用方法、统计实践和计算决策背后的历史和推理,以确保 MMDx 评分尽可能准确和精确。MMDx 可从相对少量的组织中深入了解疾病过程和高度可重复的结果,是一种通用方法,可用于医学的许多领域,包括肾脏、心脏、肺和肝脏移植,并有可能为了解原生器官疾病状态提供借鉴。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical science
Clinical science 医学-医学:研究与实验
CiteScore
11.40
自引率
0.00%
发文量
189
审稿时长
4-8 weeks
期刊介绍: Translating molecular bioscience and experimental research into medical insights, Clinical Science offers multi-disciplinary coverage and clinical perspectives to advance human health. Its international Editorial Board is charged with selecting peer-reviewed original papers of the highest scientific merit covering the broad spectrum of biomedical specialities including, although not exclusively: Cardiovascular system Cerebrovascular system Gastrointestinal tract and liver Genomic medicine Infection and immunity Inflammation Oncology Metabolism Endocrinology and nutrition Nephrology Circulation Respiratory system Vascular biology Molecular pathology.
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