Motivation: Modern methods of whole transcriptome sequencing accurately recover nucleotide sequences of RNA molecules present in cells and allow for determining their quantitative abundances. The coding potential of such molecules can be estimated using open reading frames (ORF) finding algorithms, implemented in a number of software packages. However, these algorithms show somewhat limited accuracy, are intended for single-molecule analysis and do not allow selecting proper ORFs in the case of

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... long mRNAs containing multiple ORF candidates. Results: We developed a computational approach, corresponding machine learning model and a package, dedicated to automatic identification of the ORFs in large sets of human mRNA molecules. It is based on vectorization of nucleotide sequences into features, followed by classification using a random forest. The predictive model was validated on sets of human mRNA molecules from the NCBI RefSeq and Ensembl databases and demonstrated almost 95% accuracy in detecting true ORFs. The developed methods and pre-trained classification model were implemented in a powerful ORFhunteR computational tool that performs an automatic identification of true ORFs among large set of human mRNA molecules. Availability and implementation: The developed open-source R package ORFhunteR is available for the community at GitHub repository (https://github.com/rfctbio-bsu/ORFhunteR), from Bioconductor (https://bioconductor.org/packages/devel/bioc/html/ORFhunteR.html) and as a web application (http://orfhunter.bsu.by).