A deep learning method to integrate extracelluar miRNA with mRNA for cancer studies.

Motivation: Extracellular 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.

Results: We 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 implementation: The datasets and tool are available at https://doi.org/10.5281/zenodo.13891508.