Counting individual RNA or DNA molecules is difficult because they are hard to copy quantitatively for detection. To overcome this limitation, we applied unique molecular identifiers (UMIs), which make each molecule in a population distinct, to genome-scale human karyotyping and mRNA sequencing in Drosophila melanogaster. Use of this method can improve accuracy of almost any next-generation sequencing method, including chromatin immunoprecipitation–sequencing, genome assembly, diagnostics and manufacturing-process control and monitoring.
We thank M. Taipale, H. Secher Lindroos, E. Ukkonen and T. Whitington for critical review of the manuscript, and E. Iwarsson (Karolinska University Hospital) for the trisomy-21 DNA. This work was supported by European Research Council project Growth Control, Academy of Finland postdoctoral researcher's projects 122197 and 134073, and the Swedish Foundation for Strategic Research grant MDB09-0052.
Supplementary Figures 1–7, Supplementary Table 1, Supplementary Note