School of Computer Science, University of Birmingham, Birmingham B15 2TT, UK.
School of Computing and Information Systems, University of Melbourne, Melbourne, VIC 3052, Australia.
Bioinformatics. 2021 Jan 29;36(21):5187-5193. doi: 10.1093/bioinformatics/btaa651.
MOTIVATION: Inferring gene regulatory networks (GRNs) from expression data is a significant systems biology problem. A useful inference algorithm should not only unveil the global structure of the regulatory mechanisms but also the details of regulatory interactions such as edge direction (from regulator to target) and sign (activation/inhibition). Many popular GRN inference algorithms cannot infer edge signs, and those that can infer signed GRNs cannot simultaneously infer edge directions or network cycles. RESULTS: To address these limitations of existing algorithms, we propose Polynomial Lasso Bagging (PoLoBag) for signed GRN inference with both edge directions and network cycles. PoLoBag is an ensemble regression algorithm in a bagging framework where Lasso weights estimated on bootstrap samples are averaged. These bootstrap samples incorporate polynomial features to capture higher-order interactions. Results demonstrate that PoLoBag is consistently more accurate for signed inference than state-of-the-art algorithms on simulated and real-world expression datasets. AVAILABILITY AND IMPLEMENTATION: Algorithm and data are freely available at https://github.com/gourabghoshroy/PoLoBag. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
动机:从表达数据推断基因调控网络(GRN)是一个重要的系统生物学问题。一个有用的推断算法不仅应该揭示调控机制的全局结构,还应该揭示调控相互作用的细节,如边缘方向(从调节剂到靶标)和符号(激活/抑制)。许多流行的 GRN 推断算法无法推断边缘符号,而那些能够推断有符号 GRN 的算法则无法同时推断边缘方向或网络循环。
结果:为了解决现有算法的这些局限性,我们提出了 Polynomial Lasso Bagging(PoLoBag)用于有符号 GRN 推断,同时推断边缘方向和网络循环。PoLoBag 是一种集成回归算法,在袋装框架中,对 bootstrap 样本估计的 Lasso 权重进行平均。这些 bootstrap 样本包含多项式特征,以捕获更高阶的相互作用。结果表明,PoLoBag 在模拟和真实表达数据集上的有符号推断比最先进的算法更准确。
可用性和实现:算法和数据可在 https://github.com/gourabghoshroy/PoLoBag 上免费获得。
补充信息:补充数据可在 Bioinformatics 在线获得。
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