Probabilistic (Bayesian) modeling of gene expression in transplant glomerulopathy

Eric A. Elster, Jason S. Hawksworth, Orlena Cheng, David B. Leeser, Michael Ring, Douglas K. Tadaki, David E. Kleiner, John S. Eberhardt, Trevor S. Brown, Roslyn B. Mannon

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Transplant glomerulopathy (TG) is associated with rapid decline in glomerular filtration rate and poor outcome. We used low-density arrays with a novel probabilistic analysis to characterize relationships between gene transcripts and the development of TG in allograft recipients. Retrospective review identified TG in 10.8% of 963 core biopsies from 166 patients; patients with stable function were studied for comparison. The biopsies were analyzed for expression of 87 genes related to immune function and fibrosis by using real-time PCR, and a Bayesian model was generated and validated to predict histopathology based on gene expression. A total of 57 individual genes were increased in TG compared with stable function biopsies (P < 0.05). The Bayesian analysis identified critical relationships between ICAM-1, IL-10, CCL3, CD86, VCAM-1, MMP-9, MMP-7, and LAMC2 and allograft pathology. Moreover, Bayesian models predicted TG when derived from either immune function (area under the curve [95% confidence interval] of 0.875 [0.675 to 0.999], P = 0.004) or fibrosis (area under the curve [95% confidence interval] of 0.859 [0.754 to 0.963], P < 0.001) gene networks. Critical pathways in the Bayesian models were also analyzed by using the Fisher exact test and had P values <0.005. This study demonstrates that evaluating quantitative gene expression profiles with Bayesian modeling can identify significant transcriptional associations that have the potential to support the diagnostic capability of allograft histology. This integrated approach has broad implications in the field of transplant diagnostics.

Original languageEnglish (US)
Pages (from-to)653-663
Number of pages11
JournalJournal of Molecular Diagnostics
Issue number5
StatePublished - Sep 2010
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine


Dive into the research topics of 'Probabilistic (Bayesian) modeling of gene expression in transplant glomerulopathy'. Together they form a unique fingerprint.

Cite this