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Epigenetic machine learning: utilizing DNA methylation patterns to predict spastic cerebral palsy.

Erin L Crowgey1, Adam G Marsh2,3, Karyn G Robinson1

  • 1Nemours Biomedical Research, Nemours - Alfred I. duPont Hospital for Children, 1600 Rockland Rd, Wilmington, DE, 19803, USA.

BMC Bioinformatics
|June 22, 2018
PubMed
Summary
This summary is machine-generated.

Epigenetic profiles in DNA methylation can identify spastic cerebral palsy (CP). This study found distinct methylation patterns in blood cells, enabling accurate diagnosis in adolescents and early detection in younger children.

Keywords:
Cerebral palsyComputational statisticsDNA methylationEpigenetic biomarkersGenomics

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Area of Science:

  • Epigenetics
  • Biomarkers
  • Neuroscience

Background:

  • Spastic cerebral palsy (CP) is a primary cause of physical disability.
  • Early diagnosis of CP is difficult due to the lack of reliable biomarkers.
  • Current diagnostic methods do not readily identify individuals with spastic CP.

Purpose of the Study:

  • To investigate epigenetic profiles as potential biomarkers for spastic CP.
  • To assess DNA methylation patterns in peripheral blood cells for CP diagnosis.
  • To develop a novel analysis pipeline for identifying CP-associated methylation differences.

Main Methods:

  • Analysis of DNA methylation patterns at single CpG site resolution.
  • Utilizing a novel analysis pipeline for peripheral blood cells.
  • Employing nonmetric multidimensional scaling and machine learning classification models.

Main Results:

  • Identification of significantly hypo- and hyper-methylated CpG sites in spastic CP patients.
  • Complete discrimination between CP and control groups using nonmetric multidimensional scaling.
  • Machine learning models achieved near-perfect accuracy using 40 or fewer CpG sites in adolescents.
  • A pilot test on younger children showed 73% accuracy.

Conclusions:

  • DNA methylation patterns in peripheral blood cells can distinguish adolescent spastic CP patients from controls.
  • A clinical diagnostic test using CpG site panels is feasible.
  • Distinguishing methylation patterns are present early in life, as shown by pilot validation in younger children.
  • This study introduces the first epigenetic assay for distinguishing CP cohorts.