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. 2020 Feb 5;10(2):253.
doi: 10.3390/ani10020253.

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

Michela Malvisi  1   2 , Nico Curti  3 , Daniel Remondini  3 , Maria Grazia De Iorio  2 , Fiorentina Palazzo  4 , Gustavo Gandini  2 , Silvia Vitali  3 , Michele Polli  2 , John L Williams  5 , Giulietta Minozzi  2
Affiliations

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

Michela Malvisi et al. Animals (Basel). .

Abstract

Paratuberculosis or Johne's disease in cattle is a chronic granulomatous gastroenteritis caused by infection with Mycobacterium avium subspecies paratuberculosis (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 (TRPV4, RIC8B, IL5RA, ERF, CDC40) showed significant differential expression between the three groups while the remaining 5 (RDM1, EPHX1, STAU1, TLE1, ASB8) 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.

Keywords: Johne’s disease; Mycobacterium avium subsp. paratuberculosis; RNAseq; biomarker discovery; bovine; combinatorial discriminant analysis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Principal Component Analysis (first 2 components) applied to the three groups of animals analyzed by RNAseq analysis (5 animals serologically positive to the ELISA test for MAP (PP), 5 ELISA-negative potentially exposed animals (NP) and 5 serologically negative unexposed control animals (NN), based on the RNA-seq profile of the 10 signature transcripts.
Figure 2
Figure 2
Plot of transcript levels for the 10 genes belonging to the signature. Some transcripts (EPHX1, IL5RA, ERF, CDC40) show a clear trend when moving from 5 animals serologically positive to the ELISA test for MAP (PP), to 5 ELISA-negative potentially exposed animals (NP) and 5 serologically negative unexposed control animals (NN).
Figure 3
Figure 3
Plot of the 123-transcript network (green nodes), with a detail of the 10-probe signature (red nodes).
See this image and copyright information in PMC

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