The large number of genomes that will be sequenced will need to be annotated with genes and other functional features. Aligning gene sequences from a related species to the target genome is an economical and highly reliable method to identify genes, unfortunately, existing tools have been lacking in sensitivity and speed. A program we reported, sim4cc, was shown to be highly accurate but is limited to comparing one cDNA with one genomic sequence. We present here an optimization of the tool, implemented in the packages sim4db and leaff. The new tool performs batch alignments of cDNA and genomic sequences in a fraction of the time required by its predecessor, and thus is very well suited for genome-wide analyses.