For many RNA molecules, the secondary structure is essential for the correct function of the RNA. Predicting RNA secondary structure from nucleotide sequences is a long-standing problem in genomics, but the prediction performance has reached a plateau over time. Traditional RNA secondary structure prediction algorithms are primarily based on thermodynamic models through free energy minimization, which imposes strong prior assumptions and is slow to run. Here, we propose a deep learning-based method, called UFold, for RNA secondary structure prediction, trained directly on annotated data and base-pairing rules. UFold proposes a novel image-like representation of RNA sequences, which can be efficiently processed by Fully Convolutional Networks (FCNs). We benchmark the performance of UFold on both within- and cross-family RNA datasets. It significantly outperforms previous methods on within-family datasets, while achieving a similar performance as the traditional methods when trained and tested on distinct RNA families. UFold is also able to predict pseudoknots accurately. Its prediction is fast with an inference time of about 160 ms per sequence up to 1500 bp in length. An online web server running UFold is available at https://ufold.ics.uci.edu. Code is available at https://github.com/uci-cbcl/UFold.

Cumulative evidence from biological experiments has confirmed that microRNAs (miRNAs) are related to many types of human diseases through different biological processes. It is anticipated that precise miRNA-disease association prediction could not only help infer potential disease-related miRNA but also boost human diagnosis and disease prevention. Considering the limitations of previous computational models, a more effective computational model needs to be implemented to predict miRNA-disease associations. In this work, we first constructed a human miRNA-miRNA similarity network utilizing miRNA-miRNA functional similarity data and heterogeneous miRNA Gaussian interaction profile kernel similarities based on the assumption that similar miRNAs with similar functions tend to be associated with similar diseases, and vice versa. Then, we constructed disease-disease similarity using disease semantic information and heterogeneous disease-related interaction data. We proposed a deep ensemble model called DeepMDA that extracts high-level features from similarity information using stacked autoencoders and then predicts miRNA-disease associations by adopting a 3-layer neural network. In addition to five-fold cross-validation, we also proposed another cross-validation method to evaluate the performance of the model. The results show that the proposed model is superior to previous methods with high robustness.

Characterizing genome-wide binding profiles of transcription factors (TFs) is essential for understanding biological processes. Although techniques have been developed to assess binding profiles within a population of cells, determining them at a single-cell level remains elusive. Here, we report scFAN (single-cell factor analysis network), a deep learning model that predicts genome-wide TF binding profiles in individual cells. scFAN is pretrained on genome-wide bulk assay for transposase-accessible chromatin sequencing (ATAC-seq), DNA sequence, and chromatin immunoprecipitation sequencing (ChIP-seq) data and uses single-cell ATAC-seq to predict TF binding in individual cells. We demonstrate the efficacy of scFAN by both studying sequence motifs enriched within predicted binding peaks and using predicted TFs for discovering cell types. We develop a new metric “TF activity score” to characterize each cell and show that activity scores can reliably capture cell identities. scFAN allows us to discover and study cellular identities and heterogeneity based on chromatin accessibility profiles.