Bioinformatic Prediction of Leader Genes in Oral Lichen Planus

Objectives: Genes involved in different biological processes form complex interaction networks.

However, only few have a high number of interactions with the other genes in the network and therefore might have an important role. In previous bioinformatics and experimental studies  concerning human T lymphocytes cell cycle, osteogenesis and periodontitis, these genes were identified and termed as "leader genes".

In this theoretical work, genes involved in human oral lichen planus (OLP) are identified and ranked according to their number of interactions, to preliminarily obtain a broader view of molecular mechanisms of OLP and plan targeted experimentations.

Methods: Genes involved or potentially involved in OLP were identified with systematic interrelated queries of several databases until identification of a final set. Interactions among genes were mapped and given a significance score using web-available STRING database. Weighted number of links (i.e. weighed sum of scores for every interactions in which each gene is involved) were calculated for each gene. Genes were clustered according to this parameter. The genes in the highest cluster were termed as leader genes.

Results: In total, 41 genes involved or potentially involved in OLP were identified. Only 7 of them were identified as leader genes. For 5 leader genes there is an already-established strong evidence of involvement in OLP; 2 new genes potentially playing an important role in this disease were identified. Six leader genes are also involved in oral carcinoma, which is a well-known complication of OLP.

Conclusions: A bioinformatic algorithm is applied to increase our knowledge of molecular mechanisms of OLP. Even with the limitations of any ab-initio analysis, this study can suggest targeted experimentation, focused on leader genes and therefore simpler than mass scale molecular genomics. The identification of leader genes might suggest new potential risk factor and therapeutic targets.