SEnSCA: Identifying possible ligand‐receptor interactions and its application in cell–cell communication inference

Abstract Multicellular organisms have dense affinity with the coordination of cellular activities, which severely depend on communication across diverse cell types. Cell–cell communication (CCC) is often mediated via ligand‐receptor interactions (LRIs). Existing CCC inference methods are limited to known LRIs. To address this problem, we developed a comprehensive CCC analysis tool SEnSCA by integrating single cell RNA sequencing and proteome data. SEnSCA mainly contains potential LRI acquisition and CCC strength evaluation. For acquiring potential LRIs, it first extracts LRI features and reduces the feature dimension, subsequently constructs negative LRI samples through K‐means clustering, finally acquires potential LRIs based on Stacking ensemble comprising support vector machine, 1D‐convolutional neural networks and multi‐head attention mechanism. During CCC strength evaluation, SEnSCA conducts LRI filtering and then infers CCC by combining the three‐point estimation approach and single cell RNA sequencing data. SEnSCA computed better precision, recall, accuracy, F1 score, AUC and AUPR under most of conditions when predicting possible LRIs. To better illustrate the inferred CCC network, SEnSCA provided three visualization options: heatmap, bubble diagram and network diagram. Its application on human melanoma tissue demonstrated its reliability in CCC detection. In summary, SEnSCA offers a useful CCC inference tool and is freely available at https://github.com/plhhnu/SEnSCA .