title: Deciphering the Duality of Clock and Growth Metabolism in a Cell Autonomous System Using NMR Profiling of the Secretome.
abstract: Oscillations in circadian metabolism are crucial to the well being of organism. Our understanding of metabolic rhythms has been greatly enhanced by recent advances in high-throughput systems biology experimental techniques and data analysis. In an in vitro setting, metabolite rhythms can be measured by time-dependent sampling over an experimental period spanning one or more days at sufficent resolution to elucidate rhythms. We hypothesized that cellular metabolic effects over such a time course would be influenced by both oscillatory and circadian-independent cell metabolic effects. Here we use nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling of mammalian cell culture media of synchronized U2 OS cells containing an intact transcriptional clock. The experiment was conducted over 48 h, typical for circadian biology studies, and samples collected at 2 h resolution to unravel such non-oscillatory effects. Our data suggest specific metabolic activities exist that change continuously over time in this settting and we demonstrate that the non-oscillatory effects are generally monotonic and possible to model with multivariate regression. Deconvolution of such non-circadian persistent changes are of paramount importance to consider while studying circadian metabolic oscillations.
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. arjunsen@upenn.edu.|Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. arjunsen@upenn.edu.
authors.forename: Arjun
authors.initials: A
authors.lastname: Sengupta
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. yksaikumari@gmail.com.|Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. yksaikumari@gmail.com.
authors.forename: Saikumari Y
authors.initials: SY
authors.lastname: Krishnaiah
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. srhoades@mail.med.upenn.edu.|Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. srhoades@mail.med.upenn.edu.
authors.forename: Seth
authors.initials: S
authors.lastname: Rhoades
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. jgrowe0923@gmail.com.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Growe
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. barry.slaff@gmail.com.|Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. barry.slaff@gmail.com.
authors.forename: Barry
authors.initials: B
authors.lastname: Slaff
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. anandven22@gmail.com.
authors.forename: Anand
authors.initials: A
authors.lastname: Venkataraman
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. olarerin@gmail.com.
authors.forename: Anthony O
authors.initials: AO
authors.lastname: Olarerin-George
authors.affiliation: Abramson Family Cancer Research Institute, Perelman Schol of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. dangvchi@exchange.upenn.edu.
authors.forename: Chi
authors.initials: C
authors.lastname: Van Dang
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. hogenesch@gmail.com.|Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, OH 45267, USA. hogenesch@gmail.com.
authors.forename: John B
authors.initials: JB
authors.lastname: Hogenesch
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. aalim@upenn.edu.|Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. aalim@upenn.edu.
authors.forename: Aalim M
authors.initials: AM
authors.lastname: Weljie
keywords: NMR spectroscopy; U2 OS; circadian oscillations; detrending; metabolomics