Identification of immune-related lncRNAs in periodontitis reveals regulation network of gene-lncRNA-pathway-immunocyte

Background: Long noncoding RNAs (lncRNAs), which is essential in regulating multiple biological functions, have been found to have pivotal roles in immune regulation. Since immune reaction and immunocytes are the key part in periodontitis progression, we aim to investigate the underlying lncRNA-immunity regulatory network of periodontitis. Methods: A series of bioinformatic algorithms were used to identify immune-related lncRNAs in periodontitis. Infiltrating immunocyte were calculated by MCP-count. Pathway activity were estimated by the GSVA. The relationships between immune-related lncRNA and periodontitis features were investigated including immune gene categories, perturbated lncRNAs, immunocytes and pathways. Immune-related periodontitis subtypes were identified by ConsensusClusterPlus algorithm. Immunocytes related gene-lncRNA modules were identified by WGCNA. Results: An integrated algorithm and pipeline to identify immune-related lncRNAs was developed and 1059 immune-related lncRNAs in 14 immune categories were identified, 291 of them were perturbated in periodontitis. An independent validation set verified the robustness of immune-related lncRNAs. A higher proportion of immune-related lncRNAs are correlated with immunocyte infiltration. Pathways associated with immune-related lncRNAs were also revealed. Two distinct immune-related periodontitis subtypes were identified according to perturbated immune-related lncRNAs with different immune and clinical characteristics, in which subtype-1 has a higher infiltrated immunocytes, higher immune reaction scores and more chronic periodontitis samples. Immunocytes and clinical phenotypes matching their gene-lncRNA modules, and their functions were annotated. Conclusions: Our study systematically investigated periodontitis immune-related lncRNAs and have taken a glimpse of the underlying mechanism of periodontitis from gene-lncRNA-immunocyte networks, which can not only inspire researchers but also help in periodontitis related immune researches.