METHODS: Known PCOS-related proteins (PCOSrp) from PCOSBase and DisGeNET were integrated with protein-protein interactions (PPI) information from Human Integrated Protein-Protein Interaction reference to construct a PCOS PPI network. The network was clustered with DPClusO algorithm to generate clusters, which were evaluated using Fisher's exact test. Pathway enrichment analysis using gProfileR was conducted to identify significant pathways.
RESULTS: The statistical significance of the identified clusters has successfully predicted 138 novel PCOSrp with 61.5% reliability and, based on Cronbach's alpha, this prediction is acceptable. Androgen signalling pathway and leptin signalling pathway were among the significant PCOS-related pathways corroborating the information obtained from the clinical observation, where androgen signalling pathway is responsible in producing male hormones in women with PCOS, whereas leptin signalling pathway is involved in insulin sensitivity.
CONCLUSIONS: These results show that graph cluster analysis can provide additional insight into the pathobiology of PCOS, as the pathways identified as statistically significant correspond to earlier biological studies. Therefore, integrative analysis can reveal unknown mechanisms, which may enable the development of accurate diagnosis and effective treatment in PCOS.
METHODS: We introduce a new node representation method based on initial information fusion, called FFANE, which amalgamates PPI networks and protein sequence data to enhance the precision of PPIs' prediction. A Gaussian kernel similarity matrix is initially established by leveraging protein structural resemblances. Concurrently, protein sequence similarities are gauged using the Levenshtein distance, enabling the capture of diverse protein attributes. Subsequently, to construct an initial information matrix, these two feature matrices are merged by employing weighted fusion to achieve an organic amalgamation of structural and sequence details. To gain a more profound understanding of the amalgamated features, a Stacked Autoencoder (SAE) is employed for encoding learning, thereby yielding more representative feature representations. Ultimately, classification models are trained to predict PPIs by using the well-learned fusion feature.
RESULTS: When employing 5-fold cross-validation experiments on SVM, our proposed method achieved average accuracies of 94.28%, 97.69%, and 84.05% in terms of Saccharomyces cerevisiae, Homo sapiens, and Helicobacter pylori datasets, respectively.
CONCLUSION: Experimental findings across various authentic datasets validate the efficacy and superiority of this fusion feature representation approach, underscoring its potential value in bioinformatics.