Fig. 1: Overall study design.
Differential expression was investigated between M. pneumoniae and virus datasets from17 (step 1). We employed a re-sampling approach (step 2) to generate 1000 transcript signatures of size n (step 3). These signatures were utilized to compute 1000 AUC values on both the training (TA) and test (TE) datasets (step 4), as well as on the non-mycoplasma bacteria and virus datasets from the EUCLIDS (discovery) cohort (step 4 and 5). Next, Signature Scores (SS) were obtained for the different n-transcript signatures (from n = 3 to 10) based on AUCTA, AUCTE, and AUCEU values (step 6), allowing to derive the best signature of size n (step 7); n-SSMAX. AUC values were then computed with the best n-transcript signatures for the comparison between M. pneumoniae vs. virus and M. pneumoniae vs. virus + other pathogens from ref. 17 (step 8). For comparative purposes, we also assessed the performance of other available signatures in the literature (step 9). Finally, the best signatures were subsequently validated in the EUCLIDS (validation cohort), DIAMONDS, and PERFORM cohorts (step 10).
