ML-DSP: Machine Learning with Digital Signal Processing for ultrafast, accurate, and scalable genome classification at all taxonomic levels

BACKGROUND: Although software tools abound for the comparison, analysis, identification, and classification of genomic sequences, taxonomic classification remains challenging due to the magnitude of the datasets and the intrinsic problems associated with classification. The need exists for an approach and software tool that addresses the limitations of existing alignment-based methods, as well as the challenges of recently proposed alignment-free methods. RESULTS: We propose a novel combination of supervised Machine Learning with Digital Signal Processing, resulting in ML-DSP: an alignment-free software tool for ultrafast, accurate, and scalable genome classification at all taxonomic levels. We test ML-DSP by classifying 7396 full mitochondrial genomes at various taxonomic levels, from kingdom to genus, with an average classification accuracy of >97%. A quantitative comparison with state-of-the-art classification software tools is performed, on two small benchmark datasets and one large 4322 vertebrate mtDNA genomes dataset. Our results show that ML-DSP overwhelmingly outperforms the alignment-based software MEGA7 (alignment with MUSCLE or CLUSTALW) in terms of processing time, while having comparable classification accuracies for small datasets and superior accuracies for the large dataset. Compared with the alignment-free software FFP (Feature Frequency Profile), ML-DSP has significantly better classification accuracy, and is overall faster. We also provide preliminary experiments indicating the potential of ML-DSP to be used for other datasets, by classifying 4271 complete dengue virus genomes into subtypes with 100% accuracy, and 4,710 bacterial genomes into phyla with 95.5% accuracy. Lastly, our analysis shows that the "Purine/Pyrimidine", "Just-A" and "Real" numerical representations of DNA sequences outperform ten other such numerical representations used in the Digital Signal Processing literature for DNA classification purposes. CONCLUSIONS: Due to its superior classification accuracy, speed, and scalability to large datasets, ML-DSP is highly relevant in the classification of newly discovered organisms, in distinguishing genomic signatures and identifying their mechanistic determinants, and in evaluating genome integrity.

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