Artificial sequences of DNA and RNA - called sequins - that emulate the complexity of the human genome are described in two papers published online this week in Nature Methods. These studies provide a reference that may help to improve the detection of rare genetic mutations associated with particular diseases.
Human genomes are a complex landscape of mutations, repeats, inversions, insertions and deletions, some of which are associated with disease. Although standard analysis techniques try to capture this complexity, with current standards it is often not clear how accurate the results are or what the analyses miss.
Tim Mercer and colleagues developed synthetic DNA and RNA standards (sequins) that represent the complexity of the genome and the genes it encodes. The authors used the sequins to show that, with current methods, many genomic regions cannot be fully analyzed and many genes, particularly those expressed at lower levels, remain undetected. By adding, or ‘spiking’, the sequins - which have a known RNA or DNA sequence - into an experiment, researchers can compare the results of their genome analysis to the results for the sequins to evaluate how sensitive their analysis methods are, what they can confidently detect and how much they are likely to miss.
The authors suggest that these sequin controls could theoretically be designed to represent any feature of the human genome or transcriptome (all of the genes that are transcribed into RNA) and improve analysis methods to more reliably detect rare mutations.