A universal and independent synthetic DNA ladder for the quantitative measurement of genomic features

Andre L. M. Reis, Ira W. Deveson, Ted Wong, Bindu Swapna Madala, Chris Barker, James Blackburn, Esteban Marcellin and Tim R. Mercer ()
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Andre L. M. Reis: Garvan Institute of Medical Research
Ira W. Deveson: Garvan Institute of Medical Research
Ted Wong: Garvan Institute of Medical Research
Bindu Swapna Madala: Garvan Institute of Medical Research
Chris Barker: Garvan Institute of Medical Research
James Blackburn: Garvan Institute of Medical Research
Esteban Marcellin: The University of Queensland
Tim R. Mercer: Garvan Institute of Medical Research

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract Standard units of measurement are required for the quantitative description of nature; however, few standard units have been established for genomics to date. Here, we have developed a synthetic DNA ladder that defines a quantitative standard unit that can measure DNA sequence abundance within a next-generation sequencing library. The ladder can be spiked into a DNA sample, and act as an internal scale that measures quantitative genetics features. Unlike previous spike-ins, the ladder is encoded within a single molecule, and can be equivalently and independently synthesized by different laboratories. We show how the ladder can measure diverse quantitative features, including human genetic variation and microbial abundance, and also estimate uncertainty due to technical variation and improve normalization between libraries. This ladder provides an independent quantitative unit that can be used with any organism, application or technology, thereby providing a common metric by which genomes can be measured.

Date: 2020
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DOI: 10.1038/s41467-020-17445-5

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