Fig. 4: Transcriptomic profile predicting potential infectiousness.

Dot plot of gene set enrichment analyses illustrating the 30 most enriched (A) and suppressed (B) gene ontology biological pathways, when comparing CAS-positive to CAS-negative individuals. The x-axis represents the number of enriched genes detected in each pathway. The dot size represents the gene ratio, which is the proportion of all genes in the pathway that were determined to be enriched or suppressed. The dot color represents the adjusted p-value as indicated in the legend. In summary, activated pathways in CAS- positive individuals included responses to biotic stimulus including virus and bacteria, innate and inflammatory immune responses as well as production and responses to cytokines and type I interferon. Pathways that are suppressed in CAS positive individuals included complement and B cell activation, phagocytosis and immunoglobulin mediated immune responses as well as pathways related to ion transport, development and neuronal sensory perception. C Enrichment map illustrating the 30 most enriched and suppressed gene ontology biological process pathways when comparing CAS-positive to CAS-negative individuals. Enriched terms are clustered into networks with edges linking gene sets with overlapping terms to identify functional modules. For activated pathways, three overlapping clustered functional modules can be identified including (i) terms related to inflammatory/innate immunity and responses to cytokines (red circle), (ii) viral defence responses including production and responses to type I interferons (blue circle) as well as (iii) pathways involved in bacterial defence responses (green circle). For repressed pathways three distinct functional modules are present including (i) pathways involved in phagocytosis, humoral immunoglobulin immunity, complement and B cell activation and receptor signaling (red circle), (ii) ion transport and neuronal signaling (blue circle) and (iii) distinct pathways involved in development/morphogenesis (green circle). The edges (grey line) link pathways with overlapping terms with shorter lengths indicating greater similarity. The dot size represents the number of enriched genes in the pathways while color represents adjusted p-values as indicated in the legend. D Selection of genes best predicting infectiousness as measured by capacity of patients to emit culture positive aerosols. PPV Positive predicting value, NPV Negative predictive value, AUC Area under curve, MIR4323 microRNA 4323, TBL1XR1 transducing (beta)-like 1X-linked WD40 repeat-containing gene, PPP3CB protein phosphatase 3 catalytic subunit beta, TRPM2 transient receptor potential cation channel, subfamily M, member 2. An F-test was used to compare CAS-positive to CAS-negative participants.