Quantifying circular RNA expression from RNA-seq data using model-based framework.

MOTIVATION: Circular RNAs (circRNAs) are a class of non-coding RNAs that are widely expressed in various cell lines and tissues of many organisms. Although the exact function of many circRNAs is largely unknown, the cell type-and tissue-specific circRNA expression has implicated their crucial functions in many biological processes. Hence, the quantification of circRNA expression from high-throughput RNA-seq data is becoming important to ascertain. Although many model-based methods have been developed to quantify linear RNA expression from RNA-seq data, these methods are not applicable to circRNA quantification. RESULTS: Here, we proposed a novel strategy that transforms circular transcripts to pseudo-linear transcripts and estimates the expression values of both circular and linear transcripts using an existing model-based algorithm, Sailfish. The new strategy can accurately estimate transcript expression of both linear and circular transcripts from RNA-seq data. Several factors, such as gene length, amount of expression and the ratio of circular to linear transcripts, had impacts on quantification performance of circular transcripts. In comparison to count-based tools, the new computational framework had superior performance in estimating the amount of circRNA expression from both simulated and real ribosomal RNA-depleted (rRNA-depleted) RNA-seq datasets. On the other hand, the consideration of circular transcripts in expression quantification from rRNA-depleted RNA-seq data showed substantial increased accuracy of linear transcript expression. Our proposed strategy was implemented in a program named Sailfish-cir. AVAILABILITY AND IMPLEMENTATION: Sailfish-cir is freely available at https://github.com/zerodel/Sailfish-cir . CONTACT: tongz@medicine.nevada.edu or wanjun.gu@gmail.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A Pathway-Based Strategy to Identify Biomarkers for Lung Cancer Diagnosis and Prognosis.

Current research has identified several potential biomarkers for lung cancer diagnosis or prognosis. However, most of these biomarkers are derived from a relatively small number of samples using algorithms at the gene level. Hence, gene expression signatures discovered in these studies have little overlaps. In this study, we proposed a new strategy to identify biomarkers from multiple datasets at the pathway level. We integrated the genome-wide expression data of lung cancer tissues from 13 published studies and applied our strategy to identify lung cancer diagnostic and prognostic biomarkers. We identified a 32-gene signature that differentiates lung adenocarcinomas from other lung cancer subtypes. We also discovered a 43-gene signature that can predict the outcome of human lung cancers. We tested their performance in several independent cohorts, which confirmed their robust prognostic and diagnostic power. Furthermore, we showed that the proposed gene expression signatures were independent of several traditional clinical indicators in lung cancer management. Our results suggest that the pathway-based strategy is useful to identify transcriptomic biomarkers from large-scale gene expression datasets that were collected from multiple sources.