StartLink and StartLink+: Prediction of Gene Starts in Prokaryotic Genomes

Abstract

State-of-the-art algorithms of ab initio gene prediction for prokaryotic genomes were shown to be sufficiently accurate. A pair of algorithms would agree on predictions of gene 3′ends. Nonetheless, predictions of gene starts would not match for 15–25% of genes in a genome. This discrepancy is a serious issue that is difficult to be resolved due to the absence of sufficiently large sets of genes with experimentally verified starts. We have introduced StartLink that infers gene starts from conservation patterns revealed by multiple alignments of homologous nucleotide sequences. We also have introduced StartLink+ combining both ab initio and alignment-based methods. The ability of StartLink to predict the start of a given gene is restricted by the availability of homologs in a database. We observed that StartLink made predictions for 85% of genes per genome on average. The StartLink+ accuracy was shown to be 98–99% on the sets of genes with experimentally verified starts. In comparison with database annotations, we observed that the annotated gene starts deviated from the StartLink+ predictions for ∼5% of genes in AT-rich genomes and for 10–15% of genes in GC-rich genomes on average. The use of StartLink+ has a potential to significantly improve gene start annotation in genomic databases.

MetaGeneMark-2: Improved Gene Prediction in Metagenomes

“…To get additional test sets we used the following approach. In our previous work (Gemayel et al 2021) we have shown that predictions of gene starts made by StartLink+ have low error rates, ~1%. Therefore, we used StartLink+ to make computational predictions of gene starts in 427 genomes including 108 archaeal, and 319 bacterial ones (104 Enterobacterales,111 Actinobacteria,and 104 FCB group).…”

“…To eliminate influence of GeneMarkS-2 we consider only the group of genes with starts inferred from the protein alignment evidence. Further on, in this group we selected genes whose starts coincided with predictions of StartLink+ (Gemayel et al 2021) supposed to have error rate ∼ 1%. This set was designated as T 3 .…”