PEAK: Integrating Curated and Noisy Prior Knowledge in Gene Regulatory Network Inference

Lenwood Heath

Abstract

With abundance of biological data, computational prediction of gene regulatory networks (GRNs) from gene expression data has become more feasible. Although incorporating other prior knowledge (PK), along with gene expression data, greatly improves prediction accuracy, the overall accuracy is still low. PK in GRN inference can be categorized into noisy and curated. In noisy PK, relations between genes do not necessarily correspond to regulatory relations and are thus considered inaccurate by inference algorithms such as transcription factor binding and protein–protein interactions. In contrast, curated PK is experimentally verified regulatory interactions in pathway databases. An issue in real data is that gene expression can poorly support the curated PK and thus most existing prediction algorithms cannot use these curated PK. Although several algorithms were proposed to incorporate noisy PK, none address curated PK with poor gene expression support. We present PEAK, a system to integrate both curated and noisy PK in GRN inference, especially with poor gene expression support. We introduce a novel method for GRN inference, CurInf, to effectively integrate curated PK, even when the gene expression data poorly support the PK. PEAK also uses the previously proposed method Modified Elastic Net to incorporate noisy PK, and we call it NoisInf. In our experiment, CurInf significantly incorporates curated PK, which was regarded as noise by previous methods. Using 100% curated PK, CurInf improves the area under precision-recall curve accuracy score over NoisInf by 27.3% in synthetic data, 86.5% in Escherichia coli data, and 31.1% in Saccharomyces cerevisiae data. Moreover, even when the noise in PK is 10 times more than true PK, PEAK performs better than inference without any PK. Better integration of curated PK helps biologists benefit from verified experimental data to predict more reliable GRN.