Sequence similarity is more relevant than species specificity in probabilistic backtranslation

This paper describes EasyBack, a new parameter-free, fully-automated software for backtranslation using Hidden Markov Models. EasyBack is not based on imitation of codon usage within the target species, but instead uses a sequence-similarity criterion. The model is trained with a set of proteins with known cDNA coding sequences, constructed from the input protein by querying the NCBI databases with BLAST. Unlike existing software, the proposed method allows the quality of prediction to be estimated. When tested on a group of proteins that show different degrees of sequence conservation, EasyBack outperforms other published methods in terms of precision.The prediction quality of a protein backtranslation methis markedly increased by replacing the criterion of most used codon in the same species with a Hidden Markov Model trained with a set of most similar sequences from all species. Moreover, the proposed method allows the quality of prediction to be estimated probabilistically.In natural systems, proteins are synthesized using template mRNA derived from molecules transcribed from the encoding genes. Backtranslation (reverse translation) reverses the normal flow of information, exploiting the primary structure of a protein to deduce the nucleotide sequence of the encoding mRNA. Backtranslation tools are basic to the construction of synthetic DNA segments (gene design systems) [1]. Such systems use suitable modules to optimize backtranslated segments to be used for expression by a host organism, or to be changed completely to accommodate various constraints [2-4].The degeneracy of the genetic code makes backtranslation potentially ambiguous since most amino acids are encoded by multiple codons. Extensive studies have been conducted on synonymous codon usage in different species and its influence in biological processes such as structure prediction [5-9].The approach to backtranslation common to all commercial and non-commercial software (BBOCUS [10], BACKTRANSEQ of th