Kato Tsuyoshi, Murata Yukio, Miura Koh, Asai Kiyoshi, Horton Paul B, Koji Tsuda, Fujibuchi Wataru
Graduate School of Frontier Sciences, University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, 277 - 8562, Japan.
BMC Bioinformatics. 2006 Mar 20;7 Suppl 1(Suppl 1):S4. doi: 10.1186/1471-2105-7-S1-S4.
Prediction of human cell response to anti-cancer drugs (compounds) from microarray data is a challenging problem, due to the noise properties of microarrays as well as the high variance of living cell responses to drugs. Hence there is a strong need for more practical and robust methods than standard methods for real-value prediction.
We devised an extended version of the off-subspace noise-reduction (de-noising) method to incorporate heterogeneous network data such as sequence similarity or protein-protein interactions into a single framework. Using that method, we first de-noise the gene expression data for training and test data and also the drug-response data for training data. Then we predict the unknown responses of each drug from the de-noised input data. For ascertaining whether de-noising improves prediction or not, we carry out 12-fold cross-validation for assessment of the prediction performance. We use the Pearson's correlation coefficient between the true and predicted response values as the prediction performance. De-noising improves the prediction performance for 65% of drugs. Furthermore, we found that this noise reduction method is robust and effective even when a large amount of artificial noise is added to the input data.
We found that our extended off-subspace noise-reduction method combining heterogeneous biological data is successful and quite useful to improve prediction of human cell cancer drug responses from microarray data.
由于微阵列的噪声特性以及活细胞对药物反应的高度变异性,从微阵列数据预测人类细胞对抗癌药物(化合物)的反应是一个具有挑战性的问题。因此,与用于实值预测的标准方法相比,迫切需要更实用、更强大的方法。
我们设计了一种扩展版的子空间外降噪方法,将序列相似性或蛋白质 - 蛋白质相互作用等异质网络数据纳入单一框架。使用该方法,我们首先对训练数据和测试数据的基因表达数据以及训练数据的药物反应数据进行降噪处理。然后,我们从降噪后的输入数据中预测每种药物的未知反应。为了确定降噪是否能提高预测效果,我们进行了12折交叉验证以评估预测性能。我们将真实反应值与预测反应值之间的皮尔逊相关系数用作预测性能指标。降噪提高了65%药物的预测性能。此外,我们发现即使在输入数据中添加大量人工噪声,这种降噪方法依然稳健且有效。
我们发现,我们扩展的结合异质生物数据的子空间外降噪方法对于改善基于微阵列数据的人类细胞癌药物反应预测是成功且非常有用的。