School of Life Sciences, Shanghai University, Shanghai, 200444, People's Republic of China.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Protein J. 2024 Jun;43(3):477-486. doi: 10.1007/s10930-024-10180-6. Epub 2024 Mar 4.
Protein-protein interactions (PPIs) involve the physical or functional contact between two or more proteins. Generally, proteins that can interact with each other always have special relationships. Some previous studies have reported that gene ontology (GO) terms are related to the determination of PPIs, suggesting the special patterns on the GO terms of proteins in PPIs. In this study, we explored the special GO term patterns on human PPIs, trying to uncover the underlying functional mechanism of PPIs. The experimental validated human PPIs were retrieved from STRING database, which were termed as positive samples. Additionally, we randomly paired proteins occurring in positive samples, yielding lots of negative samples. A simple calculation was conducted to count the number of positive samples for each GO term pair, where proteins in samples were annotated by GO terms in the pair individually. The similar number for negative samples was also counted and further adjusted due to the great gap between the numbers of positive and negative samples. The difference of the above two numbers and the relative ratio compared with the number on positive samples were calculated. This ratio provided a precise evaluation of the occurrence of GO term pairs for positive samples and negative samples, indicating the latent GO term patterns for PPIs. Our analysis unveiled several nuclear biological processes, including gene transcription, cell proliferation, and nutrient metabolism, as key biological functions. Interactions between major proliferative or metabolic GO terms consistently correspond with significantly reported PPIs in recent literature.
蛋白质-蛋白质相互作用(PPIs)涉及两个或多个蛋白质之间的物理或功能接触。通常,能够相互作用的蛋白质总是有特殊的关系。一些先前的研究报告称,基因本体论(GO)术语与 PPI 的确定有关,这表明 PPI 中蛋白质的 GO 术语存在特殊模式。在这项研究中,我们探索了人类 PPI 上的特殊 GO 术语模式,试图揭示 PPI 的潜在功能机制。从 STRING 数据库中检索到经实验验证的人类 PPI,将其称为阳性样本。此外,我们随机配对阳性样本中出现的蛋白质,产生了大量的阴性样本。对每个 GO 术语对的阳性样本数量进行了简单的计算,其中样本中的蛋白质分别由该对中的 GO 术语注释。还计算了阴性样本的相似数量,并由于阳性和阴性样本数量之间存在巨大差距而进行了进一步调整。计算上述两个数量之间的差异以及与阳性样本数量的相对比值。该比值为阳性样本和阴性样本中 GO 术语对的发生提供了精确的评估,表明了 PPI 的潜在 GO 术语模式。我们的分析揭示了一些核生物学过程,包括基因转录、细胞增殖和营养代谢,作为关键的生物学功能。主要增殖或代谢 GO 术语之间的相互作用与最近文献中报道的显著 PPI 一致。