When this correlation remained significant (P<0.05), then the biomarker was defined as convergent-application biomarker (Figure 6b).
Catalase activity emerged as a convergent-application biomarker for lethal oxidative stress robustness, which could be elicited by multiple mild stress pretreatments (e.g. mild heat, acid and oxidative stress) (see also Figure 8).
The transcripts of both clpC and clpP were qualified as convergent-application biomarkers for lethal acid stress robustness upon mild acid and mild salt stress pretreatment (Figure S4 and S5 in the supplementary material).
The predictive potential of the transcripts clpC and clpP were comparable and both were qualified as convergent-application biomarkers for lethal acid stress robustness following mild acid and mild salt stress preexposure.
Next to SigB, also the proteins ClpC and ClpP were qualified as convergent-application biomarkers for lethal heat stress robustness, but their potential to predict this stress adaptive behavior was related to mild heat and mild acid stress pretreated cells.
Since SigB could predict the robustness status towards lethal heat stress of both mild heat and mild salt stress pretreated cells, and remained significantly correlated to lethal heat stress robustness when these mild heat and mild salt stress induced responses were combined, SigB was qualified as convergent-application biomarker for lethal heat stress robustness.
A concluding overview of the predictive potential of the candidate-biomarkers is presented in Table 1 and 2. The SigB protein was suitable to predict the robustness enhancement towards lethal heat stress upon mild heat and mild salt stress pretreatment and was therefore qualified as convergent-application biomarker for lethal heat stress robustness (Table 1, see also Figure 7).
Because, catalase activity could still predict the robustness status towards lethal oxidative stress when these three mild stress induced responses were combined, it pointed to the potential of catalase activity to act as a vigorous convergent-application biomarker for lethal oxidative stress robustness.
In addition to SigB protein, also the proteins ClpC and ClpP were identified as convergent-application biomarkers for lethal heat stress robustness, but their predictive potential was related to mild heat and mild acid stress pretreated cells (see Figure S2 and S3 in the supplementary material).
This problem has been used to model various problems in applications but convergent solution algorithms are extremely scare in the literature.
CITH was the starter of new developments as well as the coordinator of a complete strategy in medical area which associates fundamental research, preclinical evaluation and clinical applications with convergent orientations and sharing experience for a better evaluation of new ultrasound methods in medical area.
