Next-generation sequencing (NGS) technologies have transformed scientific approaches in basic and applied research by enabling enormous volumes of DNA sequencing data at low cost. The tradeoff to this advantage, however, is that NGS technologies generally produce primary read data of lower quality compared with those created by the gold standard, Sanger sequencing. Efforts to overcome this limitation are seldom reported in genome costs, yet they can be significant. Innovations in creating a novel nucleotide chemistry paradigm have resulted in improved accuracy of the primary data, which will inherently reduce genome cost. Benefits of the LaserGen system are afforded by the novel chemistry, Lightning Terminators™ which deliver high quality data, reducing the need for over-sampling, thus lowering the IT burden. LaserGen Lightning Terminators™ are also backward-compatible with most commercial sequencing instruments.