Signalling pathways are conserved across different species, therefore making yeast a model organism to study these via disruption of kinase activity. Yeast has 159 genes that encode protein kinases and phosphatases, and 136 of these have counterparts in humans. Therefore any insight in this model organism could potentially offer indications of mechanisms of action in the human kinome. The study utilises a Prolog-based approach, data from a yeast kinase deletions strains study and publicly available kinase-protein associations. Prolog, a programming language that is well-suited for symbolic reasoning is used to reason over the data and infer compensatory kinase networks. This approach is based on the idea that when a kinase is knocked out, other kinases may compensate for this loss of activity. Background knowledge on kinases targeting proteins is used to guide the analysis. This knowledge is used to infer the potential compensatory interactions between kinases based on the changes in phosphorylation observed in the phosphoproteomics data from the yeast study. The results demonstrate the effectiveness of the Prolog-based approach in analysing complex cell signalling mechanisms in yeast. The inferred compensatory kinase networks provide new insights into the regulation of cell signalling in yeast and may aid in the identification of potential therapeutic targets for modulating signalling pathways in yeast and other organisms.

翻译：信号通路在不同物种间具有保守性，因此酵母成为通过破坏激酶活性来研究这些通路的模式生物。酵母拥有159个编码蛋白激酶和磷酸酶的基因，其中136个在人类中有对应基因。因此，对这一模式生物的任何认识都可能为人类激酶组的调控机制提供潜在启示。本研究采用基于Prolog的方法，结合酵母激酶缺失菌株研究数据及公开的激酶-蛋白关联数据。Prolog作为一种适用于符号推理的编程语言，被用于对数据进行推理并推断补偿性激酶网络。该方法基于以下理念：当某个激酶被敲除时，其他激酶可能补偿其活性损失。利用激酶靶向蛋白的背景知识引导分析，并基于酵母研究中磷酸化蛋白质组学数据所观测到的磷酸化变化，推断激酶间潜在的补偿性相互作用。结果证明了基于Prolog的方法在分析酵母复杂细胞信号传导机制中的有效性。推断出的补偿性激酶网络为酵母细胞信号调控提供了新见解，并可能有助于识别调节酵母及其他生物信号通路的潜在治疗靶点。