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Drug-Target Interaction (DTI) prediction facilitates acceleration of drug discovery and promotes drug repositioning. Most existing deep learning-based DTI prediction methods can better extract discriminative features for drugs and proteins, but they rarely consider multimodal features of drugs. Moreover, learning the interaction representations between drugs and targets needs further exploration. Here, we proposed a simple M  ulti-modal G  ating N  etwork for DTI prediction, MGNDTI, based on multimodal representation learning and the gating mechanism. MGNDTI first learns the sequence representations of drugs and targets using different retentive networks. Next, it extracts molecular graph features of drugs through a graph convolutional network. Subsequently, it devises a multimodal gating network to obtain the joint representations of drugs and targets. Finally, it builds a fully connected network for computing the interaction probability. MGNDTI was benchmarked against seven state-of-the-art DTI prediction models (CPI-GNN, TransformerCPI, MolTrans, BACPI, CPGL, GIFDTI, and FOTF-CPI) using four data sets (i.e., Human, C. elegans , BioSNAP, and BindingDB) under four different experimental settings. Through evaluation with AUROC, AUPRC, accuracy, F1 score, and MCC, MGNDTI significantly outperformed the above seven methods. MGNDTI is a powerful tool for DTI prediction, showcasing its superior robustness and generalization ability on diverse data sets and different experimental settings. It is freely available at https://github.com/plhhnu/MGNDTI.

Background: Cell-cell communication in a tumor microenvironment is vital to tumorigenesis, tumor progression and therapy. Intercellular communication inference helps understand molecular mechanisms of tumor growth, progression and metastasis., Methods: Focusing on ligand-receptor co-expressions, in this study, we developed an ensemble deep learning framework, CellComNet, to decipher ligand-receptor-mediated cell-cell communication from single-cell transcriptomic data. First, credible LRIs are captured by integrating data arrangement, feature extraction, dimension reduction, and LRI classification based on an ensemble of heterogeneous Newton boosting machine and deep neural network. Next, known and identified LRIs are screened based on single-cell RNA sequencing (scRNA-seq) data in certain tissues. Finally, cell-cell communication is inferred by incorporating scRNA-seq data, the screened LRIs, a joint scoring strategy that combines expression thresholding and expression product of ligands and receptors., Results: The proposed CellComNet framework was compared with four competing protein-protein interaction prediction models (PIPR, XGBoost, DNNXGB, and OR-RCNN) and obtained the best AUCs and AUPRs on four LRI datasets, elucidating the optimal LRI classification ability. CellComNet was further applied to analyze intercellular communication in human melanoma and head and neck squamous cell carcinoma (HNSCC) tissues. The results demonstrate that cancer-associated fibroblasts highly communicate with melanoma cells and endothelial cells strong communicate with HNSCC cells., Conclusions: The proposed CellComNet framework efficiently identified credible LRIs and significantly improved cell-cell communication inference performance. We anticipate that CellComNet can contribute to anticancer drug design and tumor-targeted therapy., Competing Interests: Declaration of Competing Interest All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The identification of lncRNA-protein interactions (LPIs) is important to understand the biological functions and molecular mechanisms of lncRNAs. However, most computational models are evaluated on a unique dataset, thereby resulting in prediction bias. Furthermore, previous models have not uncovered potential proteins (or lncRNAs) interacting with a new lncRNA (or protein). Finally, the performance of these models can be improved. In this study, we develop a Deep Learning framework with Dual-net Neural architecture to find potential LPIs (LPI-DLDN). First, five LPI datasets are collected. Second, the features of lncRNAs and proteins are extracted by Pyfeat and BioTriangle, respectively. Third, these features are concatenated as a vector after dimension reduction. Finally, a deep learning model with dual-net neural architecture is designed to classify lncRNA-protein pairs. LPI-DLDN is compared with six state-of-the-art LPI prediction methods (LPI-XGBoost, LPI-HeteSim, LPI-NRLMF, PLIPCOM, LPI-CNNCP, and Capsule-LPI) under four cross validations. The results demonstrate the powerful LPI classification performance of LPI-DLDN. Case study analyses show that there may be interactions between RP11-439E19.10 and Q15717, and between RP11-196G18.22 and Q9NUL5. The novelty of LPI-DLDN remains, integrating various biological features, designing a novel deep learning-based LPI identification framework, and selecting the optimal LPI feature subset based on feature importance ranking.

Objective. To go beyond the deficiencies of the three conventional multimodal fusion strategies (i.e. input-, feature- and output-level fusion), we propose a bidirectional attention-aware fluid pyramid feature integrated fusion network (BAF-Net) with cross-modal interactions for multimodal medical image diagnosis and prognosis. Approach. BAF-Net is composed of two identical branches to preserve the unimodal features and one bidirectional attention-aware distillation stream to progressively assimilate cross-modal complements and to learn supplementary features in both bottom-up and top-down processes. Fluid pyramid connections were adopted to integrate the hierarchical features at different levels of the network, and channel-wise attention modules were exploited to mitigate cross-modal cross-level incompatibility. Furthermore, depth-wise separable convolution was introduced to fuse the cross-modal cross-level features to alleviate the increase in parameters to a great extent. The generalization abilities of BAF-Net were evaluated in terms of two clinical tasks: (1) an in-house PET-CT dataset with 174 patients for differentiation between lung cancer and pulmonary tuberculosis. (2) A public multicenter PET-CT head and neck cancer dataset with 800 patients from nine centers for overall survival prediction. Main results. On the LC-PTB dataset, improved performance was found in BAF-Net (AUC = 0.7342) compared with input-level fusion model (AUC = 0.6825; p < 0.05), feature-level fusion model (AUC = 0.6968; p = 0.0547), output-level fusion model (AUC = 0.7011; p < 0.05). On the H&N cancer dataset, BAF-Net (C-index = 0.7241) outperformed the input-, feature-, and output-level fusion model, with 2.95%, 3.77%, and 1.52% increments of C-index (p = 0.3336, 0.0479 and 0.2911, respectively). The ablation experiments demonstrated the effectiveness of all the designed modules regarding all the evaluated metrics in both datasets. Significance. Extensive experiments on two datasets demonstrated better performance and robustness of BAF-Net than three conventional fusion strategies and PET or CT unimodal network in terms of diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Carcinomas are complex ecosystems composed of cancer, stromal and immune cells. Communication between these cells and their microenvironments induces cancer progression and causes therapy resistance. In order to improve the treatment of cancers, it is essential to quantify crosstalk between and within various cell types in a tumour microenvironment. Focusing on the coordinated expression patterns of ligands and cognate receptors, cell–cell communication can be inferred through ligand–receptor interactions (LRIs). In this manuscript, we carry out the following work: (i) introduce pipeline for ligand–receptor-mediated intercellular communication estimation from single-cell transcriptomics and list a few available LRI-related databases and visualization tools; (ii) demonstrate seven classical intercellular communication scoring strategies, highlight four types of representative intercellular communication inference methods, including network-based approaches, machine learning-based approaches, spatial information-based approaches and other approaches; (iii) summarize the evaluation and validation avenues for intercellular communication inference and analyze the advantages and limitations for the above four types of cell–cell communication methods; (iv) comment several major challenges while provide further research directions for intercellular communication analysis in the tumour microenvironments. We anticipate that this work helps to better understand intercellular crosstalk and to further develop powerful cell–cell communication estimation tools for tumor-targeted therapy. [ABSTRACT FROM AUTHOR]