Sensitivity and specificity of pulse detection using a new deconvolution method

Peter Y. Liu, Daniel M. Keenan, Petra Kok, Vasantha Padmanabhan, Kevin T. O'Byrne, Johannes D Veldhuis

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Quantifying pulsatile secretion from serial hormone concentration measurements (deconvolution analysis) requires automated, objective, and accurate detection of pulse times to ensure valid estimation of secretion and elimination parameters. Lack of validated pulse identification constitutes a major deficiency in the deconvolution field, because individual pulse size and number reflect regulated processes that are critical for the function and response of secretory glands. To evaluate deconvolution pulse detection accuracy, four empirical models of true-positive markers of pituitary (LH) pulses were used. 1) Sprague-Dawley rats had recordings of hypothalamic arcuate nucleus multiunit electrical activity, 2) ovariectomized ewes underwent sampling of hypothalamo-pituitary gonadotropin-releasing hormone (GnRH pulses), 3) healthy young men were infused with trains of biosynthetic LH pulses after GnRH receptor blockade, and 4) computer simulations of pulsatile LH profiles were constructed. Outcomes comprised sensitivity, specificity, and receiver-operating characteristic curves. Sensitivity and specificity were 0.93 and 0.97, respectively, for combined empirical data in the rat, sheep, and human (n = 156 pulses) and 0.94 and 0.92, respectively, for computer simulations (n = 1,632 pulses). For simulated data, pulse-set selection by the Akaike information criterion yielded slightly higher sensitivity than by the Bayesian information criterion, and the reverse was true for specificity. False-positive errors occurred primarily at low-pulse amplitude, and false-negative errors occurred principally with close pulse proximity. Random variability (noise), sparse sampling, and rapid pulse frequency reduced pulse detection sensitivity more than specificity. We conclude that an objective automated pulse detection deconvolution procedure has high sensitivity and specificity, thus offering a platform for quantitative neuroendocrine analyses.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume297
Issue number2
DOIs
StatePublished - Aug 2009

Fingerprint

Sensitivity and Specificity
Gonadotropin-Releasing Hormone
Computer Simulation
LHRH Receptors
Pituitary Gonadotropins
Arcuate Nucleus of Hypothalamus
Pituitary Hormones
ROC Curve
Sprague Dawley Rats
Noise
Sheep
Hormones
Datasets

Keywords

  • Analytical model
  • Biostatistics
  • Elimination
  • Human
  • Luteinizing hormone
  • Male
  • Rat
  • Secretion
  • Sheep

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Sensitivity and specificity of pulse detection using a new deconvolution method. / Liu, Peter Y.; Keenan, Daniel M.; Kok, Petra; Padmanabhan, Vasantha; O'Byrne, Kevin T.; Veldhuis, Johannes D.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 297, No. 2, 08.2009.

Research output: Contribution to journalArticle

Liu, Peter Y. ; Keenan, Daniel M. ; Kok, Petra ; Padmanabhan, Vasantha ; O'Byrne, Kevin T. ; Veldhuis, Johannes D. / Sensitivity and specificity of pulse detection using a new deconvolution method. In: American Journal of Physiology - Endocrinology and Metabolism. 2009 ; Vol. 297, No. 2.
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