TY - JOUR T1 - Unsupervised Network Analysis of the Plastic Supraoptic Nucleus Transcriptome Predicts Caprin-2 Regulatory Interactions JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0243-17.2017 SP - ENEURO.0243-17.2017 AU - Su-Yi Loh AU - Thomas Jahans-Price AU - Michael P. Greenwood AU - Mingkwan Greenwood AU - See-Ziau Hoe AU - Agnieszka Konopacka AU - Colin Campbell AU - David Murphy AU - Charles C. T. Hindmarch Y1 - 2017/11/30 UR - http://www.eneuro.org/content/early/2017/11/30/ENEURO.0243-17.2017.abstract N2 - The supraoptic nucleus (SON) is a group of neurones in the hypothalamus responsible for the synthesis and secretion of the peptide hormones vasopressin and oxytocin. Following physiological cues, such as dehydration, salt-loading and lactation, the SON undergoes a function related plasticity that we have previously described in the rat at the transcriptome level. Using the unsupervised Graphical Lasso (Glasso) algorithm, we reconstructed a putative network from 500 plastic SON genes in which genes are the nodes and the edges are the inferred interactions. The most active nodal gene identified within the network was RNA binding protein Caprin2. Caprin2 is an RNA binding protein that we have previously shown to be vital for the functioning of osmoregulatory neuroendocrine neurones in the SON of the rat hypothalamus. To test the validity of the Glasso network, we either over-expressed or knocked-down Caprin2 transcripts in differentiated rat pheochromocytoma PC12 cells, and showed that these manipulations had significant opposite effects on the levels of putative target mRNAs. These studies suggest that the predicative power of the Glasso algorithm within an in vivo system is accurate, and identifies biological targets that may be important to the functional plasticity of the SON.Significance Statement The scale and complexity of transcriptome datasets makes the identification of suitable targets for physiologic studies a daunting problem. Using the unsupervised Glasso algorithm, we reconstructed a putative network from 500 plastic genes in the supraoptic nucleus of the hypothalamus. The most active nodal gene identified within the network encodes RNA binding protein Caprin2. We tested the validity of the Glasso network by either over-expressing or knocking-down Caprin-2 transcripts in differentiated rat pheochromocytoma cells, and showed that these manipulations had opposite effects on the levels of putative target mRNAs. Our studies suggest that the predicative power of the Glasso algorithm can identify biological targets that may be important in a Caprin2 gene network mediating functional plasticity in the SON. ER -