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The primary goal of the study was to determine differences between the microbiomes of healthy (HLT), pneumonic (POS), and previously pneumonic (PRV) calves from a single dairy farm dealing with a high prevalence of Mycoplasmopsis bovis. 16S rRNA sequencing was completed by Norgen Biotek Corp. on the Illumina MiSeq platform. All fastq sequences generated are accessible on NCBI's Sequence Read Archive repository under the BioProject accession number PRJNA1389668. Amplicon sequence variants (ASVs) were constructed using DADA2 in QIIME2. Taxonomic classification was completed using the SILVA v138 reference database. Subsequent analyses were completed in R Statistics. This dataset includes the sample metadata (Supplementary Table 1), relative abundance distribution across genera and species (Supplementary Table 2), the differential abundance results from the ANCOM-BC2 analysis using the ANCOMBC v1.2.8 R package (Supplementary Table 3), and the taxa-taxa correlation results from the SECOM analysis which was also implemented in the ANCOMBC R package (Supplementary Table 4). Our study focused on Mycoplasmopsis bovis (M. bovis) abundance in pneumonic calves. Briefly, we found that M. bovis was more associated with the loss of commensal taxa that were enriched in healthy animals and was significantly enriched in pneumonia positive animals. Overall, these findings suggest that M. bovis is associated with dysbiosis within the respiratory microbiota and may influence BRD pathogenesis. ANCOM-BC2 data displays the log2 fold change, p-value, and BH-adjusted q-value as well as other differential abundance metrics for each comparison. For clinical group comparisons, healthy animals were the reference. SECOM data outlines the taxa-taxa abundance correlations for each taxa among the dataset. Both nonlinear (distance) and linear (Pearson) correlation was calculated and the associated BH-adjusted p-value.