Jin Xiaoxiao, Ma Xia, Zhu Ying
Department of Gynecology and Obstetrics, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China.
Department of Gynecology and Obstetrics, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China
Ann Clin Lab Sci. 2019 Sep;49(5):598-607.
This study aimed to investigate dysregulated sub-pathways for preeclampsia (PE) infants based on lncRNA-mRNA expression profiles and pathway network.
The inference of dysregulated sub-pathways consisted of four steps: extracting candidate lncRNA-mRNA interactions from validated lncRNA-miRNA and miRNA-mRNA interactions; capturing seed lncRNA-mRNA pairs from candidate lncRNA-mRNA interactions; embedding lncRNAs of seed lncRNA-mRNA pairs into significant pathways, and constructing a network for lncRNAs competing regulated pathways (LCRPs), followed by hub nodes identification; and exploring candidate sub-pathways based on the shortest path and estimating their significance by the Wallenius approximation method to select dysregulated sub-pathways for PE.
1,473 seed lncRNA-mRNA pairs involved 105 seed lncRNAs and 742 seed mRNAs were obtained. Based on them, we investigated 35 LCRPs for PE infants. The network for LCRPs was consisted of 532 nodes and 1,840 edges, of which 62 hub lncRNAs were identified. Further, a total of 38 dysregulated sub-pathways were determined from candidate sub-pathways under the condition of <1.00E-05. values for dysregulated sub-pathways were nearly zero, which indicated their great significance between PE infants and controls.
Identifying competitively dysregulated sub-pathways could provide better understanding into the origin and development of PE, as well as assist in clarifying the functions of important lncRNAs.
本研究旨在基于lncRNA-mRNA表达谱和通路网络,探究子痫前期(PE)患儿失调的子通路。
失调子通路的推断包括四个步骤:从已验证的lncRNA-miRNA和miRNA-mRNA相互作用中提取候选lncRNA-mRNA相互作用;从候选lncRNA-mRNA相互作用中捕获种子lncRNA-mRNA对;将种子lncRNA-mRNA对中的lncRNAs嵌入重要通路,并构建lncRNAs竞争调控通路(LCRPs)网络,随后识别枢纽节点;基于最短路径探索候选子通路,并通过瓦伦纽斯近似法估计其显著性,以选择PE的失调子通路。
获得了涉及105个种子lncRNAs和742个种子mRNAs的1473个种子lncRNA-mRNA对。基于这些,我们研究了PE患儿的35条LCRPs。LCRPs网络由532个节点和1840条边组成,其中识别出62个枢纽lncRNAs。此外,在<1.00E-05的条件下,从候选子通路中确定了总共38条失调子通路。失调子通路的 值几乎为零,这表明它们在PE患儿和对照组之间具有重要意义。
识别竞争性失调的子通路可以更好地理解PE的起源和发展,并有助于阐明重要lncRNAs的功能。