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Temporal dynamics in laboratory medicine: cosinor analysis and real-world data (RWD) approaches to population chronobiology

  • Fernando Marques-Garcia ORCID logo EMAIL logo , Cristina Martinez-Bravo , Xavier Tejedor-Ganduxe and Ruben Fossion
Published/Copyright: February 19, 2025
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 7

Abstract

Objectives

Chronobiology is the science that studies biological rhythms based on direct methods and empirical time series of individual subjects. In laboratory medicine, the factor of time is often underestimated, and no methods currently exist to study biological rhythms in population databases of point-like, real-world data (RWD).

Methods

Retrospective databases (24 months, 2022–2023) were extracted for four measurands (sodium, potassium, chloride and leukocytes) from the emergency laboratory. Two different strategies for data grouping were applied: data clouds (with or without outliers) and population-averaged profiles. Cosinor regression analysis was performed on the grouped data to derive circadian parameters. The parameters obtained here were compared to results from the literature, using direct methods and time series.

Results

A total of 409,719 data points were analyzed. All measurands exhibited symmetrical data distributions, except for leukocytes. The data clouds did not visually display rhythmicity, but cosinor analysis revealed a significant circadian rhythm. The removal of outliers had minimal impact on the results. In contrast, population-averaged profiles showed visible rhythmicity, which was confirmed by cosinor analysis with a better goodness-of-fit compared to the data clouds.

Conclusions

Population-averaged profiles have advantages over data clouds in characterizing circadian rhythms and deriving circadian parameters. Population chronobiology, based on RWD, is presented as an alternative to classical individual chronobiology, based on time series and overcomes the limitations of direct methods. Utilizing RWD provides new insights into the relationship between chronobiology and clinical laboratory practice.

Keywords: population chronobiology; cosinor; data clouds; population-averaged profiles
Corresponding author: Fernando Marques-Garcia, PhD, Clinical Biochemistry Department, Metropolitan Nord Clinical Laboratory (LUMN), Germans Trias i Pujol University Hospital, 08916, Badalona, Barcelona, Spain, E-mail:

Funding source: DGAPA-UNAM

Award Identifier / Grant number: PAPIIT IN115124

  1. Research ethics: Protocol approved PI-21-034.

  2. Informed consent: Not applicable.

  3. Author contributions: FMG: Conceived and designed the analysis; Contributed data or analysis tools; Performed the analysis; Wrote the paper. CMB: Conceived and designed the analysis; Contributed data or analysis tools; Performed the analysis; Wrote the paper. XTG: Contributed data or analysis tools; Wrote the paper. RF: Conceived and designed the analysis; Contributed data or analysis tools; Performed the analysis; Wrote the paper. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: Financial funding for this work was supplied by the Dirección General de Asuntos del Personal Académico (DGAPA) from the Universidad Nacional Autónoma de México (UNAM) with grant PAPIIT IN115124.

  7. Data availability: Not applicable.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2024-1198).

Received: 2024-10-14
Accepted: 2025-01-29
Published Online: 2025-02-19
Published in Print: 2025-06-26

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2024-1198
Keywords for this article
population chronobiology; cosinor; data clouds; population-averaged profiles

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. The journey to pre-analytical quality
  4. Manual tilt tube method for prothrombin time: a commentary on contemporary relevance
  5. Reviews
  6. From errors to excellence: the pre-analytical journey to improved quality in diagnostics. A scoping review
  7. Advancements and challenges in high-sensitivity cardiac troponin assays: diagnostic, pathophysiological, and clinical perspectives
  8. Opinion Paper
  9. Is it feasible for European laboratories to use SI units in reporting results?
  10. Perspectives
  11. What does cancer screening have to do with tomato growing?
  12. Computer simulation approaches to evaluate the interaction between analytical performance characteristics and clinical (mis)classification: a complementary tool for setting indirect outcome-based analytical performance specifications
  13. Genetics and Molecular Diagnostics
  14. Artificial base mismatches-mediated PCR (ABM-PCR) for detecting clinically relevant single-base mutations
  15. Candidate Reference Measurement Procedures and Materials
  16. Antiphospholipid IgG Certified Reference Material ERM®-DA477/IFCC: a tool for aPL harmonization?
  17. General Clinical Chemistry and Laboratory Medicine
  18. External quality assessment of the manual tilt tube technique for prothrombin time testing: a report from the IFCC-SSC/ISTH Working Group on the Standardization of PT/INR
  19. Simple steps to achieve harmonisation and standardisation of dried blood spot phenylalanine measurements and facilitate consistent management of patients with phenylketonuria
  20. Inclusion of pyridoxine dependent epilepsy in expanded newborn screening programs by tandem mass spectrometry: set up of first and second tier tests
  21. Analytical performance evaluation and optimization of serum 25(OH)D LC-MS/MS measurement
  22. Towards routine high-throughput analysis of fecal bile acids: validation of an enzymatic cycling method for the quantification of total bile acids in human stool samples on fully automated clinical chemistry analyzers
  23. Analytical and clinical evaluations of Snibe Maglumi® S100B assay
  24. Prevalence and detection of citrate contamination in clinical laboratory
  25. Reference Values and Biological Variations
  26. Temporal dynamics in laboratory medicine: cosinor analysis and real-world data (RWD) approaches to population chronobiology
  27. Establishing sex- and age-related reference intervals of serum glial fibrillary acid protein measured by the fully automated lumipulse system
  28. Hematology and Coagulation
  29. Performance of the automated digital cell image analyzer UIMD PBIA in white blood cell classification: a comparative study with sysmex DI-60
  30. Cancer Diagnostics
  31. Flow-cytometric MRD detection in pediatric T-ALL: a multicenter AIEOP-BFM consensus-based guided standardized approach
  32. Impact of biological and genetic features of leukemic cells on the occurrence of “shark fins” in the WPC channel scattergrams of the Sysmex XN hematology analyzers in patients with chronic lymphocytic leukemia
  33. Assessing the clinical applicability of dimensionality reduction algorithms in flow cytometry for hematologic malignancies
  34. Cardiovascular Diseases
  35. Evaluation of sex-specific 0-h high-sensitivity cardiac troponin T thresholds for the risk stratification of non-ST-segment elevation myocardial infarction
  36. Retraction
  37. The first case of Teclistamab interference with serum electrophoresis and immunofixation
  38. Letters to the Editor
  39. Is this quantitative test fit-for-purpose?
  40. Reply to “Is this quantitative test fit-for-purpose?”
  41. Short-term biological variation of coagulation and fibrinolytic measurands
  42. The first case of Teclistamab interference with serum electrophoresis and immunofixation
  43. Imlifidase: a new interferent on serum protein electrophoresis looking as a rare plasma cell dyscrasia
  44. Research on the development of image-based Deep Learning (DL) model for serum quality recognition
  45. Interference of hypertriglyceridemia on total cholesterol assay with the new CHOL2 Abbott method on Architect analyser
  46. Congress Abstracts
  47. 10th Annual Meeting of the Austrian Society for Laboratory Medicine and Clinical Chemistry (ÖGLMKC)
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