Prediction of personalized microRNA activity

• Published in: Gene 2013-04, Vol.518 (1), p.101-106
• Main Authors: Lee, Chuan-Chun, Yen, Chia-Jui, Liu, Tsunglin
• Format: Article
• Language: English
• Subjects: Carcinoma, Hepatocellular - genetics; Computational Biology - methods; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms - genetics; MicroRNA; MicroRNA activity prediction; MicroRNAs; Neoplasms - genetics; Personalized medicine; Reference Values; Reproducibility of Results; Software; Untranslated Regions
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2012.11.068

MicroRNAs have been known to regulate almost all physiological and pathological processes by suppressing their target genes. In humans, more than 1000microRNAs have been identified, each of which targets dozens or even hundreds of genes. Facing this huge repertoire of microRNA targeting, it is important to identify which microRNAs are active, i.e., down-regulating their targets, in specific physiological or pathological conditions. Predicting active microRNAs is different from predicting microRNA targets because the authentic target genes of a microRNA are often not directly and solely regulated by that microRNA, leading to inconsistent expression changes between the microRNA and its true targets. Several computational programs have been proposed to predict the activity of a microRNA from the expressions of its target genes. These programs performed well when being applied on the expression data obtained from distinct tissue types or from experiments that transfect a microRNA into cells (i.e., non-physiological). But the performance of microRNA activity prediction is not clear on the expression data from the same tissue type in two physiological conditions, e.g., liver tissues from cancer patients and healthy people. In this work, we evaluate the performance of two microRNA activity prediction programs using seven expression data sets, all of which compare samples in two physiological conditions, as well as propose a new approach that predicts microRNA activity with an accuracy of over 80%. Unlike current methods, which predict active microRNAs by comparing two groups of samples, e.g., tumor versus normal, our new approach compares each diseased sample with all the samples in the control group. In other words, it can predict the microRNA activity of a person. In this work, this new application is named to predict “personalized microRNA activity”. ► MicroRNA activity predictions on physiological data yield high false positives. ► The high false positive rates are partly explained by low microRNA signals. ► PicTar, a microRNA target prediction program, enhances microRNA signals. ► Treating individuals separately avoids blurring of microRNA signals. ► Personalized activity prediction is accurate for highly dys-regulated microRNAs.