Original title: Markov models of SHAPE data improve secondary structure prediction
Yifan Yang, David Mathews, Sharon Aviran · September 2026
RNA molecules fold into specific shapes to control how cells work. Scientists use experiments like SHAPE to measure which parts of an RNA chain are flexible and which parts pair up into stems. Computer programs use these experimental signals to predict an RNA molecule's shape. However, existing programs assume each measurement along the RNA strand is completely independent, ignoring real-world patterns between neighboring building blocks. To solve this, researchers converted SHAPE measurements into distinct steps and built Markov models, which are statistical tools that track patterns where one event depends directly on the one before it. These models recognize signature patterns in loops and stems, and they classify small structural shapes. When the researchers combined these models and specific signals from stable loop motifs into folding algorithms, the software predicted RNA shapes more accurately than current leading methods. This shows that accounting for nearby signals helps algorithms map RNA much better.
You are assembling a jigsaw puzzle by looking at each piece's color one at a time. But pieces belonging to the same region share similar colors, so treating them independently leads to mistakes. In this paper, the researchers instead consider the sequence of nearby pieces to detect these regional patterns and use that information to assemble the puzzle more accurately. Here, the puzzle pieces are positions along an RNA molecule and their colors are experimental measurements of flexibility.
Researchers studying RNA's role in gene regulation and disease rely on structural predictions from chemical probing experiments. Current methods treat each measurement in isolation, missing important patterns between nearby positions. This work captures those patterns, leading to more accurate structure predictions, especially in loop regions where traditional methods struggle. Better RNA structures mean deeper insights into cellular processes and improved targets for drug design.
The abstract doesn't say. It acknowledges that loop regions remain challenging due to high variance and that the framework focuses on SHAPE data. The work does not address long-range interactions or other probing methods, and discretization may lose fine-grained information.
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Markov models of SHAPE data improve secondary structure prediction — Yifan Yang, David Mathews, Sharon Aviran — bioRxiv — doi:10.64898/2026.09.10.750790
Abstract licence: CC BY
Explanation generated by Synthesis from the abstract — it is not the original paper. This is a preprint, so it hasn't necessarily been peer reviewed.