Evaluation and integration of cancer gene classifiers: identification and ranking of plausible drivers.
Evaluation and integration of cancer gene classifiers: identification and ranking of plausible drivers.
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DOI：
10.1038/srep10204
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发表时间：
2015-05-11
影响因子：
4.6
通讯作者：
DeLisi C
中科院分区：
文献类型：
--
作者：
Liu Y;Tian F;Hu Z;DeLisi C
癌细胞中突变基因的数量远远大于驱动癌症的突变数量。这为识别相关变化带来了困难，刺激了各种计算方法的发展，以区分驾驶员和旁观者。我们开发并应用了一种集成分类器（EC）机器学习方法，该方法集成了10个公开可用的分类器，并将其应用于乳腺癌和卵巢癌。特别是，我们发现以下内容：(1)使用标准和非标准指标，EC几乎总是优于单一方法分类器，通常是很大的差距。(2)在OMIM、CGC或NCG数据库中排名最高的50个乳腺癌（卵巢癌）基因中，34（30）个与其他癌症相关（P < 10−22）。(3)另外10种治疗乳腺癌和卵巢癌的药物已被GWAS研究发现。(4)剩余的几个基因——包括调节fr -1转录因子的蛋白激酶，该因子在ER阴性乳腺癌细胞中过度表达；以及Fyn（在胰腺癌和前列腺癌中过度表达）在生物学上是合理的。简要讨论了生物学意义。源代码和详细的结果可在http://www.visantnet.org/misi/driver_integration.zip。
The number of mutated genes in cancer cells is far larger than the number of mutations that drive cancer. The difficulty this creates for identifying relevant alterations has stimulated the development of various computational approaches to distinguishing drivers from bystanders. We develop and apply an ensemble classifier (EC) machine learning method, which integrates 10 classifiers that are publically available, and apply it to breast and ovarian cancer. In particular we find the following: (1) Using both standard and non-standard metrics, EC almost always outperforms single method classifiers, often by wide margins. (2) Of the 50 highest ranked genes for breast (ovarian) cancer, 34 (30) are associated with other cancers in either the OMIM, CGC or NCG database (P < 10−22). (3) Another 10, for both breast and ovarian cancer, have been identified by GWAS studies. (4) Several of the remaining genes--including a protein kinase that regulates the Fra-1 transcription factor which is overexpressed in ER negative breast cancer cells; and Fyn, which is overexpressed in pancreatic and prostate cancer, among others--are biologically plausible. Biological implications are briefly discussed. Source codes and detailed results are available at http://www.visantnet.org/misi/driver_integration.zip.