Learning biomarkers of pluripotent stem cells in mouse.

Learning biomarkers of pluripotent stem cells in mouse.
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DOI:
10.1093/dnares/dsr016
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发表时间:
2011-08
期刊:
DNA research : an international journal for rapid publication of reports on genes and genomes
影响因子:
--
通讯作者:
Fuellen G
Fuellen G
中科院分区:
其他
文献类型:
--
作者:
Scheubert L;Schmidt R;Repsilber D;Lustrek M;Fuellen G

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多能干细胞能够自我更新,并分化为所有类型的成体细胞。许多研究报告了描述这些细胞的数据,并从分子角度对它们进行了表征。机器学习可以产生能够准确识别多能干细胞的分类器,但缺乏产生最好的生物标记物(基因/特征)的最小集合的研究。我们收集了小鼠多能干细胞和非多能细胞的基因表达数据。经过归一化和过滤后,我们应用了机器学习,将样本分为多个样本和非多个样本,具有较高的交叉验证准确率。此外,为了识别最佳生物标志物的最小集合,我们使用了三种方法:信息增益、随机森林和遗传算法和支持向量机的包装器(GA/支持向量机)。我们证明遗传算法/支持向量机生物标记物相互结合的效果最好;途径分析和富集化分析表明,它们涵盖了与多能性有关的最广泛的各种过程。无论使用哪种分类方法,GA/支持向量机包装器都会产生最好的生物标志物。基于这三种方法一致认为最好的生物标记物是Tet1,最近才被发现与多能性有关。仅基于遗传算法/支持向量机包装方法的最佳生物标记是Fam134b,这可能是多能性与高尔基仪器处理的一些未知功能的标准表面标记之间缺失的一环。
Pluripotent stem cells are able to self-renew, and to differentiate into all adult cell types. Many studies report data describing these cells, and characterize them in molecular terms. Machine learning yields classifiers that can accurately identify pluripotent stem cells, but there is a lack of studies yielding minimal sets of best biomarkers (genes/features). We assembled gene expression data of pluripotent stem cells and non-pluripotent cells from the mouse. After normalization and filtering, we applied machine learning, classifying samples into pluripotent and non-pluripotent with high cross-validated accuracy. Furthermore, to identify minimal sets of best biomarkers, we used three methods: information gain, random forests and a wrapper of genetic algorithm and support vector machine (GA/SVM). We demonstrate that the GA/SVM biomarkers work best in combination with each other; pathway and enrichment analyses show that they cover the widest variety of processes implicated in pluripotency. The GA/SVM wrapper yields best biomarkers, no matter which classification method is used. The consensus best biomarker based on the three methods is Tet1, implicated in pluripotency just recently. The best biomarker based on the GA/SVM wrapper approach alone is Fam134b, possibly a missing link between pluripotency and some standard surface markers of unknown function processed by the Golgi apparatus.
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