Abstract
We developed a targeted chromosome conformation capture (4C) approach that uses unique molecular identifiers (UMIs) to derive high-complexity quantitative chromosome contact profiles with controlled signal-to-noise ratios. UMI-4C detects chromosomal interactions with improved sensitivity and specificity, and it can easily be multiplexed to allow robust comparison of contact distributions between loci and conditions. This approach may open the way to the incorporation of contact distributions into quantitative models of gene regulation.
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Acknowledgements
Research in the Tanay Lab was supported by the European Research Council, the MODHEP project and the Israeli Science Foundation. Research in the Izraeli Lab was supported by the Israel Science Foundation, the Waxman Cancer Research Foundation and the Dotan Center for Hematological Malignancies at Tel Aviv University. This work was performed in partial fulfillment of the requirements for a PhD degree by O.S.
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O.S., S.I. and A.T. designed the study. O.S. and Z.M. developed the experimental protocol with help and reagents from N.O.-E., P.O.-C., Y.L. and G.L. O.S. performed experiments. O.S. and A.T. analyzed the data and developed the pipeline. O.S. and A.T. wrote the paper. S.I. and A.T. supervised research.
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Supplementary Text and Figures
Supplementary Figures 1–10 and Supplementary Tables 1–4 (PDF 17266 kb)
Supplementary Software
UMI-4C analysis software. (ZIP 1488 kb)
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Schwartzman, O., Mukamel, Z., Oded-Elkayam, N. et al. UMI-4C for quantitative and targeted chromosomal contact profiling. Nat Methods 13, 685–691 (2016). https://doi.org/10.1038/nmeth.3922
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DOI: https://doi.org/10.1038/nmeth.3922
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