Human Disease


Small RNA


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Non-coding ribonucleic acids (RNAs), which do not encode proteins, include ribosomal RNAs, transfer RNAs, microRNAs (miRNA), piwi-interacting RNAs (piRNAs) and other RNA species. These RNAs participate in a surprisingly diverse collection of regulatory events (Moazed 2009). miRNAs have received particular attention due to their negative role in widespread regulation of mRNA metabolism through direct base pairing interactions at transcriptional and post-transcriptional levels (Carthew and Sontheimer 2009). To better understand the regulatory roles of miRNAs and other small RNAs in different tissues and developmental stages, the expression profiles of small RNAs need to be assessed.

Recently, the emergence of the next generation sequencing (NGS) techniques has revolutionized the identification of small RNAs with particularly high levels of sensitivity and accuracy (Zhou, Li et al. 2011). Several published tools detecting non-coding RNA profiles from NGS data have been developed. For example, miRExpress (Wang, Lin et al. 2009) is a stand-alone software for detecting known miRNAs and novel miRNAs. miRanalyzer (Hackenberg, Sturm et al. 2009), which also offers stand-alone version, is a web server tool that can detect known and novel miRNAs, identify differentially expressed miRNAs and predict miRNA targets. SeqBuster (Pantano, Estivill et al. 2010), offering a web-based toolkit and stand-alone version, focuses on detecting miRNA variants/isoforms for known miRNAs and can also be used to identify differentially expressed miRNAs and predict miRNA targets. There are several recent comprehensive tools designed to analyse NGS data. mirTools (Zhu, Zhao et al. 2010) is a web-based tool designed to explore the genome map and length distribution of short reads and to classify them into known categories, to detect differentially expressed miRNAs and to predict novel miRNAs and their secondary structures. DARIO (Fasold, Langenberger et al. 2011) is a free web service for detecting and normalizing non-coding RNA expression and predicting novel non-coding RNAs. WapRNA (Zhao, Liu et al. 2011) is not used only to detect miRNA expression profile from small RNA NGS data but also to analyse mRNA NGS data (detailed overview of CPSS and other 13 bioinformtics tools are shown in Supplementary Table S1). Until now, none of the currently available tools provides functional analysis for predicted targets of miRNAs from NGS data, which could help users to find potentially candidate genes/pathways for further experimental or computational studies. Thus, a comprehensive and systematic tool, integrating most features of previous tools with functional analysis for predicted targets of miRNAs from NGS data, is still needed.

Herein, we present a novel and free web server, CPSS, which integrates most functions of currently available bioinformatics tools (Supplementary Table S1 and Supplementary Fig. S1). By using CPSS, small RNA NGS data can be analysed systematically in one platform after a single submission of data by integration of annotation and functional analysis of novel and/or differentially expressed miRNAs. CPSS generates an analysis report including: (i) annotation analysis, which provides a comprehensive analysis for small RNA transcriptome, such as length distribution and genome mapping of sequencing reads, small RNA annotation, prediction of novel miRNAs, identification of differentially expressed miRNAs, piRNAs and other non-coding small RNAs between paired samples and detection of miRNA editing and modifications and (ii) functional analysis, which provides the functional analysis of miRNAs, e.g. predicting miRNA target genes by multi-tools, enriching gene ontology (GO) terms, performing signalling pathways and analysing protein–protein interaction (PPI) for the predicted genes (Fig. 1).

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