detecting regulatory mechanisms in endocrine time series measurements在内分泌时间序列测量检测监管机制.pdfVIP

Detecting Regulatory Mechanisms in Endocrine Time Series Measurements 1,2,3 2,3 2,3 4 Daniel J. Vis *, Johan A. Westerhuis , Huub C. J. Hoefsloot , Ferdinand Roelfsema , Margriet M. W. B. Hendriks1,3., Age K. Smilde2,3. 1 Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands, 2 Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands, 3 Netherlands Metabolomics Centre, Leiden, The Netherlands, 4 Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands Abstract The regulatory mechanisms underlying pulsatile secretion are complex, especially as it is partly controlled by other hormones and the combined action of multiple agents. Regulatory relations between hormones are not directly observable but may be deduced from time series measurements of plasma hormone concentrations. Variation in plasma hormone levels are the resultant of secretion and clearance from the circulation. A strategy is proposed to extract inhibition, activation, thresholds and circadian synchronicity from concentration data, using particular association methods. Time delayed associations between hormone concentrations and/or extracted secretion pulse profiles reveal the information on regulatory mechanisms. The above mentioned regulatory mechanisms are illustrated with simulated data. Additionally, data from a lean cohort of healthy control subjects is used to illustrate activation (ACTH and cortisol) and circadian synchronicity (ACTH and TSH) in real data. The simulation and the real data both consist of 145 equi