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使用 4 维免疫数据评估疾病发病机制的动态和复杂性。

Assessing the Dynamics and Complexity of Disease Pathogenicity Using 4-Dimensional Immunological Data.

机构信息

School of Medicine, Center for Global Health-Division of Infectious Diseases, University of New Mexico, Albuquerque, NM, United States.

Human Ecology, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Mérida, Mexico.

出版信息

Front Immunol. 2019 Jun 12;10:1258. doi: 10.3389/fimmu.2019.01258. eCollection 2019.

DOI:10.3389/fimmu.2019.01258
PMID:31249569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6582751/
Abstract

Investigating disease pathogenesis and personalized prognostics are major biomedical needs. Because patients sharing the same diagnosis can experience different outcomes, such as survival or death, physicians need new personalized tools, including those that rapidly differentiate several inflammatory phases. To address these topics, a pattern recognition-based method (PRM) that follows an inverse problem approach was designed to assess, in <10 min, eight concepts, and explanatory (pathogenesis). By creating thousands of secondary combinations derived from blood leukocyte data, the PRM measures synergic, pleiotropic, complex and dynamic data interactions, which provide personalized prognostics while some undesirable features-such as false results and the ambiguity associated with data circularity-are prevented. Here, this method is compared to Principal Component Analysis (PCA) and evaluated with data collected from hantavirus-infected humans and birds that appeared to be healthy. When human data were examined, the PRM predicted 96.9 % of all surviving patients while PCA did not distinguish outcomes. Demonstrating applications in personalized prognosis, eight PRM data structures sufficed to identify all but one of the survivors. Dynamic data patterns also distinguished survivors from non-survivors, as well as one subset of non-survivors, which exhibited chronic inflammation. When the PRM explored avian data, it differentiated immune profiles consistent with no, early, or late inflammation. Yet, PCA did not recognize patterns in avian data. Findings support the notion that immune responses, while variable, are rather deterministic: a low number of complex and dynamic data combinations may be enough to, rapidly, unmask conditions that are neither directly observable nor reliably forecasted.

摘要

研究疾病发病机制和个性化预后是主要的生物医学需求。由于具有相同诊断的患者可能会经历不同的结果,例如存活或死亡,因此医生需要新的个性化工具,包括能够快速区分几个炎症阶段的工具。为了解决这些问题,设计了一种基于模式识别的方法 (PRM),该方法采用逆问题方法来评估<10 分钟内的八个概念和解释性(发病机制)。通过创建源自血液白细胞数据的数千个次要组合,PRM 测量协同,多效,复杂和动态的数据相互作用,从而提供个性化的预后,同时防止了一些不理想的特征,例如假结果和与数据循环相关的歧义。在这里,将该方法与主成分分析(PCA)进行了比较,并使用从感染汉坦病毒的人类和鸟类中收集的数据进行了评估,这些人类和鸟类似乎健康。当检查人类数据时,PRM 预测了所有幸存患者的 96.9%,而 PCA 无法区分结果。通过个性化预后应用证明,八个 PRM 数据结构足以识别所有幸存者,而仅漏掉一个幸存者。动态数据模式还区分了幸存者和非幸存者,以及表现出慢性炎症的非幸存者的一个子集。当 PRM 探索鸟类数据时,它区分了与无炎症,早期炎症或晚期炎症一致的免疫谱。然而,PCA 无法识别鸟类数据中的模式。研究结果支持这样一种观点,即免疫反应虽然可变,但具有很强的确定性:少量复杂而动态的数据组合可能足以快速揭示既无法直接观察也无法可靠预测的条件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cdd/6582751/e74f4a4f91c9/fimmu-10-01258-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cdd/6582751/995ab97619a4/fimmu-10-01258-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cdd/6582751/e74f4a4f91c9/fimmu-10-01258-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cdd/6582751/995ab97619a4/fimmu-10-01258-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cdd/6582751/e74f4a4f91c9/fimmu-10-01258-g0003.jpg

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