RNA molecules can adopt stable secondary and tertiary structures, which are essential in mediating physical interactions with other partners such as RNA binding proteins (RBPs) and in carrying out their cellular functions. In vivo and in vitro experiments such as RNAcompete and eCLIP have revealed in vitro binding preferences of RBPs to RNA oligomers and in vivo binding sites in cells. Analysis of these binding data showed that the structure properties of the RNAs in these binding sites are important determinants of the binding events; however, it has been a challenge to incorporate the structure information into an interpretable model. Here we describe a new approach, RNANetMotif, which takes predicted secondary structure of thousands of RNA sequences bound by an RBP as input and uses a graph theory approach to recognize enriched subgraphs. These enriched subgraphs are in essence shared sequence-structure elements that are important in RBP-RNA binding. To validate our approach, we performed RNA structure modeling via coarse-grained molecular dynamics folding simulations for selected 4 RBPs, and RNA-protein docking for LIN28B. The simulation results, e.g., solvent accessibility and energetics, further support the biological relevance of the discovered network subgraphs.

Identifying significant biclusters of genes with specific expression patterns is an effective approach to reveal functionally correlated genes in gene expression data. However, none of existing algorithms can simultaneously identify both broader and narrower biclusters due to their failure of balancing between effectiveness and efficiency. We introduced ARBic, an algorithm which is capable of accurately identifying any significant biclusters of any shape, including broader, narrower and square, in any large scale gene expression dataset. ARBic was designed by integrating column-based and row-based strategies into a single biclustering procedure. The column-based strategy borrowed from RecBic, a recently published biclustering tool, extracts narrower biclusters, while the row-based strategy that iteratively finds the longest path in a specific directed graph, extracts broader ones. Being tested and compared to other seven salient biclustering algorithms on simulated datasets, ARBic achieves at least an average of 29% higher recovery, relevance and$\ {F}_1$ scores than the best existing tool. In addition, ARBic substantially outperforms all tools on real datasets and is more robust to noises, bicluster shapes and dataset types.

Introduction: It is expected that certain driver mutations may alter the gene expression of their associated or interacting partners, including cognate proteins. Method: We introduced DEGdriver, a novel method that can discriminate between mutations in drivers and passengers by utilizing gene differential expression at the individual level. Result: After being tested on eleven TCGA cancer datasets, DEGdriver substantially outperformed cutting-edge approaches in distinguishing driver genes from passengers and exhibited robustness to varying parameters and protein-protein interaction networks. Conclusion: Through enrichment analysis, we prove that DEGdriver can identify functional modules or pathways in addition to novel driver genes.