RNAcode Tofacitinib citrate combines amino acid substitution with gap patterns to assess the coding potential [77]. There are also methods that explore the conservation of RNA secondary structures to identify lncRNAs, including programs QRNA [78], RNAz [79], and EvoFOLD [80]. However, this approach is limited by lack of common conserved secondary structures specific for lncRNAs.Machine Learning Strategies ��Owing to the complex identities of lncRNAs, recently an increasing number of machine learning-based methods have been developed to integrate various sources of data to distinguish lncRNAs from mRNAs. Table 1 summarizes the machine learning methods and the features used to train the model for identifying lncRNAs.

For instance, CONC utilizes a series of protein features such as amino acid composition, secondary structure, and peptide length, to train a SVM model that distinguishes lncRNAs from mRNAs [18]. CPC (Coding Potential Calculator) also uses SVM for modeling and extracting sequence features and the comparative genomics features to assess the coding potential of transcripts [19, 20]. Lu et al. developed a machine learning method that integrates GC content, DNA conservation, and expression information to predict lncRNAs in C. elegans [21]. Table 1Machine-learning methods for identifying lncRNAs.Although the above-described methods have shown their effectiveness in identifying lncRNAs, exceptional cases still remain. For instance, whether an RNA transcript is translated or not may be changeable during the course of evolution. As an example, Xist, a well-known lncRNA, evolves from a protein-coding gene [81].

Besides, some genes are bifunctional, and both the coding and noncoding isoforms exist. The steroid receptor RNA activator (SRA) was characterized as a noncoding RNA previously but the coding product was detected later [82]. Such ambiguity will be clarified when more about lncRNAs are known. 4. lncRNA FunctionlncRNAs have once been thought as the ��dark matter�� of the genome, because of our limited knowledge about their functions [83]. With more studies about lncRNAs conducted, it has become clear that AV-951 lncRNAs have many specific functional features, and are likely to be involved in many diverse biological processes in cells. Rather than ��dark matter,�� they may act as necessary functional parts in the genome.