Modelling disease risk for amyloid A (AA) amyloidosis in non-human primates using machine learning

Eric T. Leung, Michael J. Raboin, Jessica McKelvey, Adam Graham, Anne Lewis, Kamm Prongay, Aaron Cohen, Amanda Vinson

Research output: Contribution to journalArticle

Abstract

Objective: Amyloid A (AA) amyloidosis is found in humans and non-human primates, but quantifying disease risk prior to clinical symptoms is challenging. We applied machine learning to identify the best predictors of amyloidosis in rhesus macaques from available clinical and pathology records. To explore potential biomarkers, we also assessed whether changes in circulating serum amyloid A (SAA) or lipoprotein profiles accompany the disease. Methods: We conducted a retrospective study using 86 cases and 163 controls matched for age and sex. We performed data reduction on 62 clinical, pathological and demographic variables, and applied multivariate modelling and model selection with cross-validation. To test the performance of our final model, we applied it to a replication cohort of 2,775 macaques. Results: The strongest predictors of disease were colitis, gastrointestinal adenocarcinoma, endometriosis, arthritis, trauma, diarrhoea and number of pregnancies. Sensitivity and specificity of the risk model were predicted to be 82%, and were assessed at 79 and 72%, respectively. Total, low density lipoprotein and high density lipoprotein cholesterol levels were significantly lower, and SAA levels and triglyceride-to-HDL ratios were significantly higher in cases versus controls. Conclusion: Machine learning is a powerful approach to identifying macaques at risk of AA amyloidosis, which is accompanied by increased circulating SAA and altered lipoprotein profiles.

Original languageEnglish (US)
Pages (from-to)139-147
Number of pages9
JournalAmyloid
Volume26
Issue number3
DOIs
StatePublished - Jul 3 2019

Keywords

  • AA amyloidosis
  • Macaca mulatta
  • dyslipidemia
  • inflammation
  • machine learning

ASJC Scopus subject areas

  • Internal Medicine

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