期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/ijms23126604
关键词
bioinformatics; chemotherapy; sensitivity analysis; molecular drug targets; systems biology
资金
- NCN [DEC-2020/37/B/ST6/01959]
- internal SUT grants [07/040/BK_22/1011, 02/040/BK_22/1022]
Mathematical modeling is crucial for experimental research on signaling pathways and regulatory networks. However, existing sensitivity analysis methods may not be suitable for biological systems. This paper introduces a novel sensitivity analysis method that is particularly designed for identifying potential molecular drug targets in signaling pathways, and demonstrates its biological relevance with two sample models.
Mathematical modeling of signaling pathways and regulatory networks has been supporting experimental research for some time now. Sensitivity analysis, aimed at finding model parameters whose changes yield significantly altered cellular responses, is an important part of modeling work. However, sensitivity methods are often directly transplanted from analysis of technical systems, and thus, they may not serve the purposes of analysis of biological systems. This paper presents a novel sensitivity analysis method that is particularly suited to the task of searching for potential molecular drug targets in signaling pathways. Using two sample models of pathways, p53/Mdm2 regulatory module and IFN-beta-induced JAK/STAT signaling pathway, we show that the method leads to biologically relevant conclusions, identifying processes suitable for targeted pharmacological inhibition, represented by the reduction of kinetic parameter values. That, in turn, facilitates subsequent search for active drug components.
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