Lam Kari Y, Westrick Zachary M, Müller Christian L, Christiaen Lionel, Bonneau Richard
New York University, New York, New York, United States of America.
Simons Foundation, New York, New York, United States of America.
PLoS Comput Biol. 2016 Dec 6;12(12):e1005157. doi: 10.1371/journal.pcbi.1005157. eCollection 2016 Dec.
Understanding gene regulatory networks is critical to understanding cellular differentiation and response to external stimuli. Methods for global network inference have been developed and applied to a variety of species. Most approaches consider the problem of network inference independently in each species, despite evidence that gene regulation can be conserved even in distantly related species. Further, network inference is often confined to single data-types (single platforms) and single cell types. We introduce a method for multi-source network inference that allows simultaneous estimation of gene regulatory networks in multiple species or biological processes through the introduction of priors based on known gene relationships such as orthology incorporated using fused regression. This approach improves network inference performance even when orthology mapping and conservation are incomplete. We refine this method by presenting an algorithm that extracts the true conserved subnetwork from a larger set of potentially conserved interactions and demonstrate the utility of our method in cross species network inference. Last, we demonstrate our method's utility in learning from data collected on different experimental platforms.
理解基因调控网络对于理解细胞分化和对外部刺激的反应至关重要。全球网络推理方法已经得到发展并应用于多种物种。大多数方法在每个物种中独立考虑网络推理问题,尽管有证据表明即使在远缘物种中基因调控也可能是保守的。此外,网络推理通常局限于单一数据类型(单一平台)和单一细胞类型。我们引入了一种多源网络推理方法,通过基于已知基因关系(如使用融合回归纳入的直系同源关系)引入先验,允许同时估计多个物种或生物过程中的基因调控网络。即使直系同源映射和保守性不完整,这种方法也能提高网络推理性能。我们通过提出一种算法来改进此方法,该算法从一组更大的潜在保守相互作用中提取真正的保守子网,并展示我们的方法在跨物种网络推理中的效用。最后,我们展示了我们的方法在从不同实验平台收集的数据中学习的效用。