Analysis and prediction of interactions between transmembrane and non-transmembrane proteins.

Background: Most of the important biological mechanisms and functions of transmembrane proteins (TMPs) are realized through their interactions with non-transmembrane proteins(nonTMPs). The interactions between TMPs and nonTMPs in cells play vital roles in intracellular signaling, energy metabolism, investigating membrane-crossing mechanisms, correlations between disease and drugs.

Results: Despite the importance of TMP-nonTMP interactions, the study of them remains in the wet experimental stage, lacking specific and comprehensive studies in the field of bioinformatics. To fill this gap, we performed a comprehensive statistical analysis of known TMP-nonTMP interactions and constructed a deep learning-based predictor to identify potential interactions. The statistical analysis describes known TMP-nonTMP interactions from various perspectives, such as distributions of species and protein families, enrichment of GO and KEGG pathways, as well as hub proteins and subnetwork modules in the PPI network. The predictor implemented by an end-to-end deep learning model can identify potential interactions from protein primary sequence information. The experimental results over the independent validation demonstrated considerable prediction performance with an MCC of 0.541.

Conclusions: To our knowledge, we were the first to focus on TMP-nonTMP interactions. We comprehensively analyzed them using bioinformatics methods and predicted them via deep learning-based solely on their sequence. This research completes a key link in the protein network, benefits the understanding of protein functions, and helps in pathogenesis studies of diseases and associated drug development.