Characterizing the circadian connectome of Ocimum tenuiflorum using an integrated network theoretic framework

Across the three domains of life, circadian clock is known to regulate vital physiological processes, like, growth, development, defence etc. by anticipating environmental cues. In this work, we report an integrated network theoretic methodology comprising of random walk with restart and graphlet degree vectors to characterize genome wide core circadian clock and clock associated raw candidate proteins in a plant for which protein interaction information is available. As a case study, we have implemented this framework in Ocimum tenuiflorum (Tulsi); one of the most valuable medicinal plants that has been utilized since ancient times in the management of a large number of diseases. For that, 24 core clock (CC) proteins were mined in 56 template plant genomes to build their hidden Markov models (HMMs). These HMMs were then used to identify 24 core clock proteins in O. tenuiflorum. The local topology of the interologous Tulsi protein interaction network was explored to predict the CC associated raw candidate proteins. Statistical and biological significance of the raw candidates was determined using permutation and enrichment tests. A total of 66 putative CC associated proteins were identified and their functional annotation was performed.