MicroRNAs (miRNAs) are a class of important non-coding RNAs, which play important roles in tumorigenesis and development by targeting oncogenes or tumor suppressor genes. One miRNA can regulate multiple genes, and one gene can be regulated by multiple miRNAs. To promote the clinical application of miRNAs, two fundamental questions should be answered: what's the regulatory mechanism of a miRNA to a gene, and which miRNAs are important for a specific type of cancer. In this study, we propose a miRNA influence capturing (miRNAInf) to decipher regulation relations of miRNAs on target genes and identify critical miRNAs in cancers in a systematic approach. With the pair-wise miRNA/gene expression profiles data, we consider the assigning problem of a miRNA on target genes and determine the regulatory mechanisms by computing the Pearson correlation coefficient between the expression changes of a miRNA and that of its target gene. Furthermore, we compute the relative local influence strength of a miRNA on its target gene. Finally, integrate the local influence strength and target gene's importance to determine the critical miRNAs involved in specific cancer. Results on breast, liver and prostate cancers show that positive regulations are as common as negative regulations. The top-ranked miRNAs show great potential as therapeutic targets driving cancer to a normal state, and they are demonstrated to be closely related to cancers based on biological functional analysis, drug sensitivity/resistance analysis and survival analysis. This study will be helpful for the discovery of critical miRNAs and development of miRNAs-based clinical therapeutics.

Pathway analysis is a common approach to gain insight from biological experiments. Signaling-pathway impact analysis (SPIA) is one such method and combines both the classical enrichment analysis and the actual perturbation on a given pathway. Because this method focuses on a single pathway, its resolution generally is not very high because the differentially expressed genes may be enriched in a local region of the pathway. In the present work, to identify cancer-related pathways, we incorporated a recent subpathway analysis method into the SPIA method to form the “sub-SPIA method.” The original subpathway analysis uses the k-clique structure to define a subpathway. However, it is not sufficiently flexible to capture subpathways with complex structure and usually results in many overlapping subpathways. We therefore propose using the minimal-spanning-tree structure to find a subpathway. We apply this approach to colorectal cancer and lung cancer datasets, and our results show that sub-SPIA can identify many significant pathways associated with each specific cancer that other methods miss. Based on the entire pathway network in the Kyoto Encyclopedia of Genes and Genomes, we find that the pathways identified by sub-SPIA not only have the largest average degree, but also are more closely connected than those identified by other methods. This result suggests that the abnormality signal propagating through them might be responsible for the specific cancer or disease.

Ischemic stroke subtyping was not only highly valuable for effective intervention and treatment, but also important to the prognosis of ischemic stroke. The manual adjudication of disease classification was time-consuming, error-prone, and limits scaling to large datasets. In this study, an integrated machine learning approach was used to classify the subtype of ischemic stroke on The International Stroke Trial (IST) dataset. We considered the common problems of feature selection and prediction in medical datasets. Firstly, the importances of features were ranked by the Shapiro-Wilk algorithm and Pearson correlations between features were analyzed. Then, we used Recursive Feature Elimination with Cross-Validation (RFECV), which incorporated linear SVC, Random-Forest-Classifier, Extra-Trees-Classifier, AdaBoost-Classifier, and Multinomial-Naïve-Bayes-Classifier as estimator respectively, to select robust features important to ischemic stroke subtyping. Furthermore, the importances of selected features were determined by Extra-Trees-Classifier. Finally, the selected features were used by Extra-Trees-Classifier and a simple deep learning model to classify the ischemic stroke subtype on IST dataset. It was suggested that the described method could classify ischemic stroke subtype accurately. And the result showed that the machine learning approaches outperformed human professionals.