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PROTECT: Protein circadian time prediction using unsupervised learning.

Aram Ansary Ogholbake1, Qiang Cheng1

  • 1Department of Internal Medicine and Department of Computer Science, University of Kentucky, Lexington, KY, USA.

Iscience
|October 23, 2025
PubMed
Summary
This summary is machine-generated.

Circadian rhythm disruption is linked to Alzheimer's disease (AD). A new deep learning method, PROTECT, analyzes proteomic data without time labels to reveal significant circadian changes in AD patients.

Keywords:
Biocomputational methodNeural networksProteinProteomics

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Area of Science:

  • Chronobiology
  • Neuroscience
  • Proteomics
  • Artificial Intelligence

Background:

  • Circadian rhythms govern human physiology, and their disruption is implicated in diseases such as Alzheimer's disease (AD).
  • Proteomic datasets often lack crucial time-label information, presenting significant challenges (small samples, high dimensionality, noise) for circadian rhythm analysis.

Purpose of the Study:

  • To introduce PROTECT, an unsupervised deep learning method for predicting circadian sample phases from unlabeled proteomic data.
  • To apply PROTECT to identify circadian disruptions in Alzheimer's disease (AD) using postmortem human brain and urine proteomic data.
  • To compare circadian patterns between AD and control subjects to understand AD-related circadian dysregulation.

Main Methods:

  • Developed PROTECT, an unsupervised deep learning algorithm utilizing greedy layer-wise pre-training and cosine-based fine-tuning.
  • Validated PROTECT's accuracy on existing time-labeled proteomic datasets.
  • Applied PROTECT to unlabeled human proteomic data from postmortem brain regions and urine samples.

Main Results:

  • PROTECT accurately predicts circadian sample phases without requiring time labels or prior knowledge of rhythmic proteins.
  • Analysis of AD proteomic data revealed significant circadian disruptions, identifying proteins with retained, lost, or altered rhythmicity.
  • Proteins maintaining rhythmicity exhibited region-specific phase shifts and amplitude changes; enrichment analysis provided functional insights into altered rhythmicity.

Conclusions:

  • PROTECT is an effective tool for circadian analysis of unlabeled proteomic data, overcoming common dataset limitations.
  • The study provides systematic evidence of circadian pattern alterations in Alzheimer's disease (AD) brain and urine proteomic data.
  • Findings highlight key proteins and functional pathways involved in AD-related circadian dysregulation, offering potential therapeutic targets.