• Media type: E-Article
  • Title: Deciphering the Transcriptomic Heterogeneity of Duodenal Coeliac Disease Biopsies
  • Contributor: Wolf, Johannes [Author]; Willscher, Edith [Author]; Loeffler-Wirth, Henry [Author]; Schmidt, Maria [Author]; Flemming, Gunter [Author]; Zurek, Marlen [Author]; Uhlig, Holm H. [Author]; Händel, Norman [Author]; Binder, Hans [Author]
  • Published: Basel: MDPI, [2024]
  • Published in: International Journal of Molecular Sciences ; 22, (2021)
  • Language: English
  • Keywords: machine learning ; villous atrophy ; personalized diagnostics ; self-organizing maps ; molecular subgroups ; gene expression signatures ; immune cell deconvolution
  • Origination:
  • Footnote:
  • Description: Coeliac disease (CD) is a clinically heterogeneous autoimmune disease with variable presentationand progression triggered by gluten intake. Molecular or genetic factors contribute to diseaseheterogeneity, but the reasons for different outcomes are poorly understood. Transcriptome studiesof tissue biopsies from CD patients are scarce. Here, we present a high-resolution analysis of thetranscriptomes extracted from duodenal biopsies of 24 children and adolescents with active CD and21 individuals without CD but with intestinal afflictions as controls. The transcriptomes of CD patientsdivide into three groups—a mixed group presenting the control cases, and CD-low and CD-highgroups referring to lower and higher levels of CD severity. Persistence of symptoms was weaklyassociated with subgroup, but the highest marsh stages were present in subgroup CD-high, togetherwith the highest cell cycle rates as an indicator of virtually complete villous atrophy. Considerablevariation in inflammation-level between subgroups was further deciphered into immune cell typesusing cell type de-convolution. Self-organizing maps portrayal was applied to provide high-resolutionlandscapes of the CD-transcriptome. We find asymmetric patterns of miRNA and long non-codingRNA and discuss the effect of epigenetic regulation. Expression of genes involved in interferongamma signaling represent suitable markers to distinguish CD from non-CD cases. Multiple pathwaysoverlay in CD biopsies in different ways, giving rise to heterogeneous transcriptional patterns,which potentially provide information about etiology and the course of the disease.
  • Access State: Open Access
  • Rights information: Attribution (CC BY)