Sequins built for the human genome.
Synthetic DNA standards representing common and clinically-important genes and mutations.
Sequins for human genome sequencing.
Next generation sequencing has become a central tool in biomedical research and clinical diagnosis. However, the complexity of the human genome, combined with errors that accumulate during NGS, confound accurate analysis and diagnosis.
Sequins are synthetic DNA standards that are ‘spiked-in’ to your DNA sample, and act as internal controls during genome sequencing. Sequins allow you to identify errors, measure diagnostic performance and improve the analysis of every NGS library.
Any human sequence can be mirrored to form a sequin sequence:
Whilst the mirrored sequin sequence is distinct, it retains the same nucleotide composition, repetitiveness and architecture as the original human sequence.
Additionally, the sequin performs equivalently to the human sequence during laboratory steps (PCR, hybridisation, library prep. and sequencing) and bioinformatic steps (alignment, variant detection etc.). Therefore, the sequin is an ideal reference standard to the original human genome sequence.
Using sequins in NGS.
Sequins are added at a fractional concentrion (typcally ~1%) to a human DNA sample. The sample and sequins then together undergo library preparation and sequencing. As the sequins accompany the sample through the NGS workflow, they accumulate the same errors and bias.
Following sequencing, the sequin reads can be distinguished from the human reads by their synthetic sequence in the output library. The sequins can then be analyzed as internal qualitative and quantitative controls.
Sequins allow you to measure the diagnostic performance (including true-positive, false-positive, and false-negative rate) for detecting different variant types in each individual NGS library.
Sequins can also be integrated with laboratory information systems to routinely monitor laboratory and bioinformatic performance, and thereby inform operational decisions.
Sequins can also measure and mitigate technical variation, enabling more accurate normalization between large patient cohorts.
These analysis (and more) can be performed using the anaquin software toolkit.
Use of synthetic DNA spike-in controls (sequins) for human genome sequencing. (2019) Blackburn et. al.,
Representing human genetic variation with synthetic DNA standards. (2016)
Deveson et. al.,
Chiral DNA sequences as commutable reference standards for clinical genomics.
(2019) Deveson et. al.,
Using sequins with human whole genome sequencing.