Combinatorial Discriminant Analysis Applied to RNAseq Data Reveals a Set of 10 Transcripts as Signatures of Exposure of Cattle to Mycobacterium avium subsp. paratuberculosis

Abstract

Paratuberculosis or Johne's disease in cattle is a chronic granulomatous gastroenteritis caused by infection with <i>Mycobacterium avium subspecies paratuberculosis</i> (MAP). Paratuberculosis is not treatable; therefore, the early identification and isolation of infected animals is a key point to reduce its incidence. In this paper, we analyse RNAseq experimental data of 5 ELISA-negative cattle exposed to MAP in a positive herd, compared to 5 negative-unexposed controls. The purpose was to find a small set of differentially expressed genes able to discriminate between exposed animals in a preclinical phase from non-exposed controls. Our results identified 10 transcripts that differentiate between ELISA-negative, clinically healthy, and exposed animals belonging to paratuberculosis-positive herds and negative-unexposed animals. Of the 10 transcripts, five (<i>TRPV4</i>, <i>RIC8B</i>, <i>IL5RA</i>, <i>ERF</i>, <i>CDC40</i>) showed significant differential expression between the three groups while the remaining 5 (<i>RDM1</i>, <i>EPHX1</i>, <i>STAU1</i>, <i>TLE1</i>, <i>ASB8</i>) did not show a significant difference in at least one of the pairwise comparisons. When tested in a larger cohort, these findings may contribute to the development of a new diagnostic test for paratuberculosis based on a gene expression signature. Such a diagnostic tool could allow early interventions to reduce the risk of the infection spreading.