Tracing the regulatory atlas of non-coding RNA in human labour

The early onset of labour increases mortality and developmental risks for a human newborn. Key genes in human labour have been investigated using multiple modalities, but their regulation by non-coding RNA (e.g. lncRNA and miRNA) remains incomplete. This study explores the three-way relationship between labour-associated transcription factors (TFs), miRNA and lncRNA suggested by the competing endogenous RNA (ceRNA) hypothesis, to understand the underlying regulatory framework. Experimentally validated miRNA-lncRNA interactions are modelled using five distinct machine learning (ML) architectures to predict 20469 labour-linked miRNA-lncRNA interactions. Known mRNA-ncRNA interactions from databases were included to construct a tripartite network, and a subset of 9989 labour-linked network motifs containing TFs were isolated and analysed. Gene enrichment of nodes in TF-lncRNA-miRNA network, as well as validation from public myometrial datasets indicate high significance in contractile pathways including immune signalling. Experimentally unconfirmed tripartite network motifs have been found, and we elaborate on their potential regulation in labour using 8 TF-lncRNA-miRNA network motifs. A unified ncRNA-TF regulatory atlas in labour has been synthesized, and a complete summary of the tripartite network motifs can be accessed and visualised using the user-friendly, public database.