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Published July 5, 2011 | Supplemental Material + Published
Journal Article Open

Modeling and automation of sequencing-based characterization of RNA structure

Abstract

Sequence census methods reduce molecular measurements such as transcript abundance and protein-nucleic acid interactions to counting problems via DNA sequencing. We focus on a novel assay utilizing this approach, called selective 2′-hydroxyl acylation analyzed by primer extension sequencing (SHAPE-Seq), that can be used to characterize RNA secondary and tertiary structure. We describe a fully automated data analysis pipeline for SHAPE-Seq analysis that includes read processing, mapping, and structural inference based on a model of the experiment. Our methods rely on the solution of a series of convex optimization problems for which we develop efficient and effective numerical algorithms. Our results can be easily extended to other chemical probes of RNA structure, and also generalized to modeling polymerase drop-off in other sequence census-based experiments.

Additional Information

© 2011 National Academy of Sciences. Freely available online through the PNAS open access option. Contributed by Jennifer A. Doudna, April 29, 2011 (sent for review February 13, 2011) S.A., J.B.L., and A.P.A. acknowledge support from the Synthetic Biology Engineering Research Center under NSF Grant 04-570/0540879. J.A.D. is an Howard Hughes Medical Institute (HHMI) Investigator, and this work was supported in part by the HHMI. S.A.M. is a fellow of the Leukemia and Lymphoma Society. J.B.L. and L.P. thank the Miller Institute for financial support and a stimulating environment in which this work was conceived. Author contributions: S.A., C.T., J.B.L., S.A.M., S.L., G.P.S., J.A.D., A.P.A., and L.P. designed research; S.A., C.T., J.B.L., S.A.M., and L.P. performed research; S.A., C.T., J.B.L., and L.P. contributed new reagents/analytic tools; S.A., C.T., J.B.L., S.A.M., S.L., and L.P. analyzed data; and S.A., C.T., J.B.L., S.A.M., S.L., G.P.S., J.A.D., A.P.A., and L.P. wrote the paper. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1106541108/-/DCSupplemental. The authors declare no conflict of interest.

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Published - PNAS-2011-Aviran-11069-74.pdf

Supplemental Material - pnas.1106541108_SI.pdf

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August 22, 2023
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