Engineered DNA Sequence Syntax Inspector

Abstract

DNAs encoding polypeptides often contain design errors that cause experiments to prematurely fail. One class of design errors is incorrect or missing elements in the DNA, here termed syntax errors. We have identified three major causes of syntax errors: point mutations from sequencing or manual data entry, gene structure misannotation, and unintended open reading frames (ORFs). The Engineered DNA Sequence Syntax Inspector (EDSSI) is an online bioinformatics pipeline that checks for syntax errors through three steps. First, ORF prediction in input DNA sequences is done by GeneMark; next, homologous sequences are retrieved by BLAST, and finally, syntax errors in the protein sequence are predicted by using the SIFT algorithm. We show that the EDSSI is able to identify previously published examples of syntactical errors and also show that our indel addition to the SIFT program is 97% accurate on a test set of Escherichia coli proteins. The EDSSI is available at http://andersonlab.qb3.berkeley.edu/Software/EDSSI/ .