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Lung Disease Diagnosis From Gene Expression Profiles

机译:从基因表达谱诊断肺部疾病

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Lung diseases include some of the most widespread and deadly conditions known toaffect people in the US today. One of the main challenges in treating lung disease is thedifficulty of diagnosis. Clinical diagnosis remains largely dependent upon symptomatic-baseddiagnoses; many cases can be either misdiagnosed or undiagnosed until disease hasprogressed to a more severe stage. Most studies aimed at finding molecular-based diagnosticshave focused on one or two diseases at a time, yielding limited success. Instead, we searchedfor biomarkers reflective of the global health state of the lung by studying data taken from abroad range of lung diseases. We used gene expression microarray data from five differentlung diseases—lung adenocarcinoma, lung squamous cell carcinoma, malignant pleuralmesothelioma, chronic obstructive pulmonary disease, and asthma—as well as a nondiseasedphenotype, to train a classification tree scheme based on the Top Scoring Pair (TSP)algorithm (Geman et al., Stat Appl Genet Mol Biol. 2004; 3: Article 19). The algorithm identified27 gene pair classifiers that classify the three cancers explicitly, and several of the markershave been previously cited in literature as linked to these cancers. Ten-fold cross validationyielded a classification accuracy of approximately 88%. Thus, a TSP-based classification treescheme accurately identifies lung diseases from the relative expression of a few number ofdiagnostic gene pairs.
机译:肺部疾病包括一些已知的最广泛和致命的疾病 影响今天的美国人民。治疗肺部疾病的主要挑战之一是 诊断困难。临床诊断在很大程度上仍取决于对症 诊断;在疾病发作之前,许多情况可能被误诊或未被诊断 进入了更严重的阶段。大多数研究旨在寻找基于分子的诊断方法 一次只关注一种或两种疾病,但收效有限。相反,我们搜索了 通过研究从肺部获取的数据来反映肺部整体健康状况的生物标志物 广泛的肺部疾病。我们使用了来自五个不同领域的基因表达微阵列数据 肺部疾病-肺腺癌,肺鳞状细胞癌,恶性胸膜 间皮瘤,慢性阻塞性肺疾病和哮喘-以及非病 表型,以训练基于最高得分对(TSP)的分类树方案 算法(Geman等人,Stat Appl Genet Mol Biol。2004; 3:第19条)。确定的算法 27个基因对分类器,对三种癌症进行了明确分类,其中一些标记 先前已在文献中被引用为与这些癌症有关。十倍交叉验证 产生大约88%的分类精度。因此,基于TSP的分类树 该方案从几个 诊断基因对。

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