Schematic view of the data structure used by RNAspa. Top: Each node carries a suboptimal secondary structure of the sequence belonging to that layer. In a top-down traversal, each node is assigned the shortest path from the top layer to itself. Next, the node with the lowest score on the lowest level is found, and the shortest path is retrieved. Bottom: The process of finding the shortest path reiterates several times. Each time, a different order permutation of the sequences is used. For each shortest path, a Sum-of-Pairs score is calculated. The shortest path with the best Sum-of-Pairs score is returned. In the illustration above, the third shortest path, which is not the shortest of the four paths, is returned because it has the best Sum-of-Pairs.