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Abstract MotivationExtracellular miRNAs (exmiRs) and intracellular mRNAs both can serve as promising biomarkers and therapeutic targets for various diseases. However, exmiR expression data is often noisy, and obtaining intracellular mRNA expression data usually involves intrusive procedures. To gain valuable insights into disease mechanisms, it is thus essential to improve the quality of exmiR expression data and develop noninvasive methods for assessing intracellular mRNA expression. ResultsWe developed CrossPred, a deep-learning multi-encoder model for the cross-prediction of exmiRs and mRNAs. Utilizing contrastive learning, we created a shared embedding space to integrate exmiRs and mRNAs. This shared embedding was then used to predict intracellular mRNA expression from noisy exmiR data and to predict exmiR expression from intracellular mRNA data. We evaluated CrossPred on three types of cancers and assessed its effectiveness in predicting the expression levels of exmiRs and mRNAs. CrossPred outperformed the baseline encoder-decoder model, exmiR or mRNA-based models, and variational autoencoder models. Moreover, the integration of exmiR and mRNA data uncovered important exmiRs and mRNAs associated with cancer. Our study offers new insights into the bidirectional relationship between mRNAs and exmiRs. Availability and implementationThe datasets and tool are available at https://doi.org/10.5281/zenodo.13891508. 

Abstract Accurate identification of microRNA (miRNA) targets at base-pair resolution has been an open problem for over a decade. The recent discovery of miRNA isoforms (isomiRs) adds more complexity to this problem. Despite the existence of many methods, none considers isomiRs, and their performance is still suboptimal. We hypothesize that by taking the isomiR–mRNA interactions into account and applying a deep learning model to study miRNA–mRNA interaction features, we may improve the accuracy of miRNA target predictions. We developed a deep learning tool called DMISO to capture the intricate features of miRNA/isomiR–mRNA interactions. Based on tenfold cross-validation, DMISO showed high precision (95%) and recall (90%). Evaluated on three independent datasets, DMISO had superior performance to five tools, including three popular conventional tools and two recently developed deep learning-based tools. By applying two popular feature interpretation strategies, we demonstrated the importance of the miRNA regions other than their seeds and the potential contribution of the RNA-binding motifs within miRNAs/isomiRs and mRNAs to the miRNA/isomiR–mRNA interactions. 

Abstract Cell–cell interactions (CCIs) are essential for multicellular organisms to coordinate biological processes and functions. One classical type of CCI interaction is between secreted ligands and cell surface receptors, i.e. ligand-receptor (LR) interactions. With the recent development of single-cell technologies, a large amount of single-cell ribonucleic acid (RNA) sequencing (scRNA-Seq) data has become widely available. This data availability motivated the single-cell-resolution study of CCIs, particularly LR-based CCIs. Dozens of computational methods and tools have been developed to predict CCIs by identifying LR-based CCIs. Many of these tools have been theoretically reviewed. However, there is little study on current LR-based CCI prediction tools regarding their performance and running results on public scRNA-Seq datasets. In this work, to fill this gap, we tested and compared nine of the most recent computational tools for LR-based CCI prediction. We used 15 well-studied scRNA-Seq samples that correspond to approximately 100K single cells under different experimental conditions for testing and comparison. Besides briefing the methodology used in these nine tools, we summarized the similarities and differences of these tools in terms of both LR prediction and CCI inference between cell types. We provided insight into using these tools to make meaningful discoveries in understanding cell communications. 

Studying miRNA activity at the single-cell level presents a significant challenge due to the limitations of existing single-cell technologies in capturing miRNAs. To address this, we introduce two deep learning models: Cross-modality (CM) and single-modality (SM), both based on encoder-decoder architectures. These models predict miRNA expression at both bulk and single-cell levels using mRNA data. We evaluated the performance of CM and SM against the state-of-the-art miRSCAPE approach, using both bulk and single-cell datasets. Our results demonstrate that both CM and SM outperform miRSCAPE in accuracy. Furthermore, incorporating miRNA target information substantially enhanced performance compared to models that utilized all genes. These models provide powerful tools for predicting miRNA expression from single-cell mRNA data. 

MicroRNAs (miRNAs) play crucial roles in gene regulation. Most studies focus on mature miRNAs, which leaves many unknowns about primary miRNAs (pri-miRNAs). To fill the gap, we attempted to model the expression of pri-miRNAs in 1829 primary cell types, cell lines, and tissues in this study. We demonstrated that the expression of pri-miRNAs can be modeled well by the expression of specific sets of mRNAs, which we termed their associated mRNAs. These associated mRNAs differ from their corresponding target mRNAs and are enriched with specific functions. Most associated mRNAs of a miRNA are shared across conditions, while on average, about one-fifth of the associated mRNAs are condition-specific. Our study shed new light on understanding miRNA biogenesis and general gene transcriptional regulation.