Discovering Regulators in Post-Transcriptional Control of the Biological Clock of <inline-formula> <tex-math notation="LaTeX">$Neurospora~crassa$ </tex-math></inline-formula> Using Variable Topology Ensemble Methods on GPUs

Abstract

In the previous paper, we reconstructed the entire transcriptional network for all 2418 clockassociated genes in the model filamentous fungus, Neurospora crassa (N. crassa). Several authors have suggested that there is extensive post-transcriptional control in the genome-wide clock network (IEEE 3: 27, 2015). Here we have successfully reconstructed the entire clock network in N. crassa with a variable topology ensemble method (VTENS), assigning each clock-associated gene to the regulation of one or more of five transcription factors as well as to six RNA operons. The resulting network provides a unifying framework to explore the clock's linkage to metabolism through post-transcriptional regulation, in which ~850 genes are predicted to fall under the regulatory control of an RNA operon. A unique feature of all of the RNA operons inferred is their functional connection to genes connected to the ribosome. We have been successful in distinguishing several hypotheses about regulatory topologies of the clock network through protein profiling of the regulators.

Keywords

• Variable topology ensemble methods
• RNA operon
• has-1%22%2C%22default_operator%22%3A%22AND%22%7D%7D%7D"> <italic xmlns:ali="http://www.niso.org/schemas/ali/1.0/" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">has-1</italic>
• lhp-1%22%2C%22default_operator%22%3A%22AND%22%7D%7D%7D"> <italic xmlns:ali="http://www.niso.org/schemas/ali/1.0/" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">lhp-1</italic>
• ribosome biogenesis
• circadian rhythms