arXiv 1803.044872018-03-08q-bio.MN

异常生物标志物富集的集成机器学习管道（i-mAB）：表征系统性红斑狼疮患者纲要中的分化簇

Integrated machine learning pipeline for aberrant biomarker enrichment (i-mAB): characterizing clusters of differentiation within a compendium of systemic lupus erythematosus patients

Trang T. Le, Nigel O. Blackwood, Jaclyn N. Taroni, Weixuan Fu, Matthew K. Breitenstein

备注：: 18 pages, 6 figures, 4 tables. Submitted on March 8, 2018 for consideration within the Proceedings of the American Medical Informatics Association 2018 Annual Symposium

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摘要：

分化簇（CD）是细胞表面生物标志物，表示细胞类型和疾病状态之间的关键生物学差异。CD靶向治疗性单克隆抗体（mAB）提供了丰富的跨疾病重新定位机会。在系统性红斑狼疮（SLE）患者的概要中，我们应用异常生物标志物富集的集成机器学习管道（i-mAB）来分析影响CD 20、CD 22和CD 30基因异常的从头基因表达特征。首先，一种新的基于缓解的算法确定了预测初治SLE患者的相互依赖特征（p=681）（平衡准确度=0.822）。然后，我们使用正则化逻辑回归和途径富集分析编译CD相关表达谱。在一个独立的通用细胞系模型系统数据上，我们复制关联（计算机模拟）BCL 7A（padj=1.69e-9）和STRBP（padj=4.63e-8）与CD 22; NCOA 2（padj=7.00e-4），ATN1（padj=1.71e-2）和HOXC 4（padj=3.34e-2）与CD 30;和PHOSPHO 1，一种与骨矿化相关的磷酸酶，具有CD 22（padj=4.37e-2）和CD 30（padj=7.40e-3）。利用仔细汇总的二级数据并利用先验假设，i-mAB在相互依赖的生物特征中促进了稳健的生物标志物分析。

英文摘要：

Clusters of differentiation (CD) are cell surface biomarkers that denote key biological differences between cell types and disease state. CD-targeting therapeutic monoclonal antibodies (mAB) afford rich trans-disease repositioning opportunities. Within a compendium of systemic lupus erythematous (SLE) patients, we applied the Integrated machine learning pipeline for aberrant biomarker enrichment (i-mAB) to profile de novo gene expression features affecting CD20, CD22 and CD30 gene aberrance. First, a novel relief-based algorithm identified interdependent features(p=681) predicting treatment-naïve SLE patients (balanced accuracy=0.822). We then compiled CD-associated expression profiles using regularized logistic regression and pathway enrichment analyses. On an independent general cell line model system data, we replicated associations (in silico) of BCL7A(padj=1.69e-9) and STRBP(padj=4.63e-8) with CD22; NCOA2(padj=7.00e-4), ATN1(padj=1.71e-2), and HOXC4(padj=3.34e-2) with CD30; and PHOSPHO1, a phosphatase linked to bone mineralization, with both CD22(padj=4.37e-2) and CD30(padj=7.40e-3). Utilizing carefully aggregated secondary data and leveraging a priori hypotheses, i-mAB fostered robust biomarker profiling among interdependent biological features.

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