Estimating autoantibody signatures to detect autoimmune disease patient subsets

Research output: Contribution to journalArticle

Abstract

Autoimmune diseases are characterized by highly specific immune responses against molecules in self-tissues. Different autoimmune diseases are characterized by distinct immune responses, making autoantibodies useful for diagnosis and prediction. In many diseases, the targets of autoantibodies are incompletely defined. Although the technologies for autoantibody discovery have advanced dramatically over the past decade, each of these techniques generates hundreds of possibilities, which are onerous and expensive to validate. We set out to establish a method to greatly simplify autoantibody discovery, using a pre-filtering step to define subgroups with similar specificities based on migration of radiolabeled, immunoprecipitated proteins on sodium dodecyl sulfate (SDS) gels and autoradiography [Gel Electrophoresis and band detection on Autoradiograms (GEA)]. Human recognition of patterns is not optimal when the patterns are complex or scattered across many samples. Multiple sources of errors including irrelevant intensity differences and warping of gelshave challenged automation of pattern discovery from autoradiograms. In this article, we address these limitations using a Bayesian hierarchical model with shrinkage priors for pattern alignment and spatial dewarping. The Bayesian model combines information from multiple gel sets and corrects spatial warping for coherent estimation of autoantibody signatures defined by presence or absence of a grid of landmark proteins. We show the pre-processing creates more clearly separated clusters and improves the accuracy of autoantibody subset detection via hierarchical clustering. Finally, we demonstrate the utility of the proposed methods with GEA data from scleroderma patients.

Original languageEnglish (US)
Pages (from-to)30-47
Number of pages18
JournalBiostatistics
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2019

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Keywords

  • Autoantibody signatures
  • Batch effect
  • Bayesian image registration
  • Clustering
  • Gel electrophoresis
  • Markov chain Monte Carlo
  • Measurement error
  • Peak detection
  • Scleroderma.

ASJC Scopus subject areas

  • Statistics and Probability
  • Statistics, Probability and Uncertainty

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