Title |
Representing genetic variation with synthetic DNA standards
|
---|---|
Published in |
Nature Methods, August 2016
|
DOI | 10.1038/nmeth.3957 |
Pubmed ID | |
Authors |
Ira W Deveson, Wendy Y Chen, Ted Wong, Simon A Hardwick, Stacey B Andersen, Lars K Nielsen, John S Mattick, Tim R Mercer |
Abstract |
The identification of genetic variation with next-generation sequencing is confounded by the complexity of the human genome sequence and by biases that arise during library preparation, sequencing and analysis. We have developed a set of synthetic DNA standards, termed 'sequins', that emulate human genetic features and constitute qualitative and quantitative spike-in controls for genome sequencing. Sequencing reads derived from sequins align exclusively to an artificial in silico reference chromosome, rather than the human reference genome, which allows them them to be partitioned for parallel analysis. Here we use this approach to represent common and clinically relevant genetic variation, ranging from single nucleotide variants to large structural rearrangements and copy-number variation. We validate the design and performance of sequin standards by comparison to examples in the NA12878 reference genome, and we demonstrate their utility during the detection and quantification of variants. We provide sequins as a standardized, quantitative resource against which human genetic variation can be measured and diagnostic performance assessed. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 13 | 37% |
Australia | 4 | 11% |
United Kingdom | 3 | 9% |
Japan | 2 | 6% |
Germany | 2 | 6% |
Belgium | 1 | 3% |
Austria | 1 | 3% |
France | 1 | 3% |
Mexico | 1 | 3% |
Other | 0 | 0% |
Unknown | 7 | 20% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 17 | 49% |
Scientists | 16 | 46% |
Practitioners (doctors, other healthcare professionals) | 1 | 3% |
Science communicators (journalists, bloggers, editors) | 1 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 5 | 3% |
Brazil | 2 | 1% |
United Kingdom | 1 | <1% |
Ireland | 1 | <1% |
Taiwan | 1 | <1% |
New Zealand | 1 | <1% |
China | 1 | <1% |
Denmark | 1 | <1% |
Unknown | 134 | 91% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 54 | 37% |
Student > Ph. D. Student | 24 | 16% |
Student > Master | 18 | 12% |
Student > Bachelor | 9 | 6% |
Other | 8 | 5% |
Other | 19 | 13% |
Unknown | 15 | 10% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 55 | 37% |
Biochemistry, Genetics and Molecular Biology | 49 | 33% |
Computer Science | 9 | 6% |
Medicine and Dentistry | 8 | 5% |
Environmental Science | 3 | 2% |
Other | 5 | 3% |
Unknown | 18 | 12% |