Simultaneous folding of alternative RNA structures with mutual constraints: an application to next-generation sequencing-based RNA structure probing
Cuncong Zhong, Department of EECS, University of Central Florida, Orlando, FL 32816-2362 USA, cczhong at eecs dot ucf dot edu
Shaojie Zhang*, Department of EECS, University of Central Florida, Orlando, FL 32816-2362 USA, shzhang at eecs dot ucf dot edu
*To whom the correspondence should be addressed to.
Recent advances in next-generation sequencing technology have significantly promoted high-throughput experimental
probing of RNA secondary structures. The resulting enzymatic or chemical probing information is then
incorporated into a minimum free energy folding algorithm to predict more accurate RNA secondary structures.
A drawback of this approach is that it does not consider the presence of alternative RNA structures. In addition,
the alternative RNA structures may contaminate experimental probing information of each other and direct
the minimum free energy folding to a wrong direction. In this article, we present a combinatorial solution for
this problem, where two alternative structures can be folded simultaneously given the experimental probing information
regarding the mixture of these two alternative structures. We have tested our algorithm with artificially
generated mixture probing data on adenine riboswitch and TPP riboswitch. The experimental results show that our
algorithm can successfully recover the ON and OFF structures of these riboswitches.