论文标题
在基因调节网络中应用的有效推断具有空间变化的高斯马尔可夫随机场
Efficient Inference of Spatially-varying Gaussian Markov Random Fields with Applications in Gene Regulatory Networks
论文作者
论文摘要
在本文中,我们研究了推断空间变化的高斯马尔可夫随机场(SV-GMRF)的问题,其中目标是学习代表基因之间网络关系的稀疏,特定于上下文的GMRF网络。 SV-GMRF的一个重要应用是推断来自空间分辨转录组学数据集的基因调节网络。当前有关SV-GMRF推断的工作基于正则最大似然估计(MLE),并且由于其高度非线性的性质而遭受了极高的计算成本。为了减轻这一挑战,我们提出了一个简单有效的优化问题,代替了配备强大的统计和计算保证的MLE。我们提出的优化问题在实践中非常有效:我们可以在不到2分钟的时间内解决具有超过200万变量的SV-GMRF的实例。我们将开发的框架应用于研究胶质母细胞瘤中的基因调节网络如何在组织中空间重新连接,并确定转录因子HES4和核糖体蛋白的显着活性,以表征肿瘤血管周围的血管周期梯形中基因表达网络,这是携带耐药性干细胞的众所周知的。
In this paper, we study the problem of inferring spatially-varying Gaussian Markov random fields (SV-GMRF) where the goal is to learn a network of sparse, context-specific GMRFs representing network relationships between genes. An important application of SV-GMRFs is in inference of gene regulatory networks from spatially-resolved transcriptomics datasets. The current work on inference of SV-GMRFs are based on the regularized maximum likelihood estimation (MLE) and suffer from overwhelmingly high computational cost due to their highly nonlinear nature. To alleviate this challenge, we propose a simple and efficient optimization problem in lieu of MLE that comes equipped with strong statistical and computational guarantees. Our proposed optimization problem is extremely efficient in practice: we can solve instances of SV-GMRFs with more than 2 million variables in less than 2 minutes. We apply the developed framework to study how gene regulatory networks in Glioblastoma are spatially rewired within tissue, and identify prominent activity of the transcription factor HES4 and ribosomal proteins as characterizing the gene expression network in the tumor peri-vascular niche that is known to harbor treatment resistant stem cells.