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From Space to Sequence and Back Again: Iterative DNA Proximity Ligation and its Applications to DNA-Based Imaging

Alexander A. Boulgakov, Erhu Xiong, Sanchita Bhadra, Andrew D. Ellington, Edward M. Marcotte
doi: https://doi.org/10.1101/470211
Alexander A. Boulgakov
1Center for Systems and Synthetic Biology, Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
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Erhu Xiong
2State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China
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Sanchita Bhadra
1Center for Systems and Synthetic Biology, Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
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Andrew D. Ellington
1Center for Systems and Synthetic Biology, Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
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Edward M. Marcotte
1Center for Systems and Synthetic Biology, Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
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  • For correspondence: marcotte@icmb.utexas.edu
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Abstract

We extend the concept of DNA proximity ligation from a single readout per oligonucleotide pair to multiple reversible, iterative ligations re-using the same oligonucleotide molecules. Using iterative proximity ligation (IPL), we can in principle capture multiple ligation events between each oligonucleotide and its various neighbors and thus recover a far richer knowledge about their relative positions than single, irreversible ligation events. IPL would thus act to sample and record local molecular neighborhoods. By integrating a unique DNA barcode into each participating oligonucleotide, we can catalog the individual ligation events and thus capture the positional information contained therein in a high throughput manner using next-generation DNA sequencing. We propose that by interpreting IPL sequencing results in the context of graph theory and by applying spring layout algorithms, we can recover geometric patterns of objects labeled by DNA. Using simulations, we demonstrate that we can in principle recover letter patterns photolithographed onto slide surfaces using only IPL sequencing data, illustrating how our technique maps complex spatial configurations into DNA sequences and then – using only this sequence information – recovers them. We complement our theoretical work with an experimental proof-of-concept of iterative proximity ligation on an oligonucleotide population.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 14, 2018.
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From Space to Sequence and Back Again: Iterative DNA Proximity Ligation and its Applications to DNA-Based Imaging
Alexander A. Boulgakov, Erhu Xiong, Sanchita Bhadra, Andrew D. Ellington, Edward M. Marcotte
bioRxiv 470211; doi: https://doi.org/10.1101/470211
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From Space to Sequence and Back Again: Iterative DNA Proximity Ligation and its Applications to DNA-Based Imaging
Alexander A. Boulgakov, Erhu Xiong, Sanchita Bhadra, Andrew D. Ellington, Edward M. Marcotte
bioRxiv 470211; doi: https://doi.org/10.1101/470211

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