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Transfer String Kernel for Cross-Context DNA-Protein Binding Prediction

机译:转换字符串内核用于跨语境DNa-蛋白质结合预测

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摘要

Through sequence-based classification, this paper tries to accurately predictthe DNA binding sites of transcription factors (TFs) in an unannotated cellularcontext. Related methods in the literature fail to perform such predictionsaccurately, since they do not consider sample distribution shift of sequencesegments from an annotated (source) context to an unannotated (target) context.We, therefore, propose a method called "Transfer String Kernel" (TSK) thatachieves improved prediction of transcription factor binding site (TFBS) usingknowledge transfer via cross-context sample adaptation. TSK maps sequencesegments to a high-dimensional feature space using a discriminative mismatchstring kernel framework. In this high-dimensional space, labeled examples ofthe source context are re-weighted so that the revised sample distributionmatches the target context more closely. We have experimentally verified TSKfor TFBS identifications on fourteen different TFs under a cross-organismsetting. We find that TSK consistently outperforms the state-of the-art TFBStools, especially when working with TFs whose binding sequences are notconserved across contexts. We also demonstrate the generalizability of TSK byshowing its cutting-edge performance on a different set of cross-context tasksfor the MHC peptide binding predictions.
机译:通过基于序列的分类,本文试图准确预测无注释细胞背景下转录因子(TF)的DNA结合位点。文献中的相关方法无法准确地执行此类预测,因为它们没有考虑序列段从带注释的(源)上下文到未带注释的(目标)上下文的样本分布偏移。因此,我们提出了一种称为“传输字符串内核”的方法( TSK)通过跨上下文样本自适应的知识转移实现了对转录因子结合位点(TFBS)的改进预测。 TSK使用区分性的不匹配字符串内核框架将序列片段映射到高维特征空间。在此高维空间中,对源上下文的标记示例进行了重新加权,以使修订后的样本分布更紧密地匹配目标上下文。我们已经在跨生物环境下对14种不同TF的TSKfor TFBS标识进行了实验验证。我们发现,TSK始终优于最新的TFBS工具,尤其是在处理绑定序列在上下文中不保守的TF时。我们还通过显示TSK在MHC肽结合预测的一组不同的跨上下文任务上的尖端性能来证明其可推广性。

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