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Circadian Rhythms and Gene Regulation02:19

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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
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Dual-Approach Co-expression Analysis Framework (D-CAF) Enables Identification of Novel Circadian Regulation From

Joshua Chuah1,2, Carmalena Cordi3, Juergen Hahn2,4

  • 1Department of Electrical, Computer, and Biomedical Engineering, Union College, 807 Union St, 12308, NY, USA,.

Biorxiv : the Preprint Server for Biology
|October 28, 2024
PubMed
Summary

A new framework, D-CAF, integrates transcript and protein data to reveal circadian control over immune responses. This tool enhances understanding of molecular timing mechanisms in biological systems.

Keywords:
co-expressionmulti-omicsproteomicsrobustnesstranscriptomics

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Area of Science:

  • Chronobiology
  • Systems Biology
  • Molecular Biology

Background:

  • The circadian clock regulates gene and protein expression, termed clock-controlled genes/proteins (CCGs/CCPs), for molecular timing.
  • Multi-omic modeling of circadian data is limited by methodological challenges, hindering a comprehensive understanding of circadian control.

Purpose of the Study:

  • To develop a novel computational framework, D-CAF, for robust co-expression analysis of time-series transcriptomic and proteomic data.
  • To apply D-CAF to identify novel circadian-regulated pathways, particularly in immunological responses.

Main Methods:

  • Developed a Dual-approach Co-expression Analysis Framework (D-CAF) for perturbation-robust analysis.
  • Applied D-CAF to analyze existing circadian time-series transcriptomic and proteomic data from mouse macrophages.
  • Utilized both unweighted and weighted similarity networks within the D-CAF framework.

Main Results:

  • Identified distinct clusters of oscillating transcripts and proteins using D-CAF, differing in significance based on network weighting.
  • Functional enrichment analysis revealed novel immunological pathways under circadian regulation.
  • Demonstrated D-CAF's capability to integrate multi-omic data for circadian analysis.

Conclusions:

  • D-CAF is an effective tool for integrating multi-omic circadian data, overcoming previous methodological limitations.
  • The study identified new circadian-controlled immunological pathways, expanding the understanding of molecular timing in immunity.
  • This framework can advance circadian research by enabling deeper insights into molecular process regulation.