The Complexity of Approximate Pattern Matching on De Bruijn Graphs

Aligning a sequence to a walk in a labeled graph is a problem of fundamental importance to Computational Biology. For finding a walk in an arbitrary graph with $|E|$ edges that exactly matches a pattern of length $m$, a lower bound based on the Strong Exponential Time Hypothesis (SETH) implies an algorithm significantly faster than $O(|E|m)$ time is unlikely [Equi et al., ICALP 2019]. However, for many special graphs, such as de Bruijn graphs, the problem can be solved in linear time [Bowe et al., WABI 2012]. For approximate matching, the picture is more complex. When edits (substitutions, insertions, and deletions) are only allowed to the pattern, or when the graph is acyclic, the problem is again solvable in $O(|E|m)$ time. When edits are allowed to arbitrary cyclic graphs, the problem becomes NP-complete, even on binary alphabets [Jain et al., RECOMB 2019]. These results hold even when edits are restricted to only substitutions. The complexity of approximate pattern matching on de Bruijn graphs remained open. We investigate this problem and show that the properties that make de Bruijn graphs amenable to efficient exact pattern matching do not extend to approximate matching, even when restricted to the substitutions only case with alphabet size four. We prove that determining the existence of a matching walk in a de Bruijn graph is NP-complete when substitutions are allowed to the graph. In addition, we demonstrate that an algorithm significantly faster than $O(|E|m)$ is unlikely for de Bruijn graphs in the case where only substitutions are allowed to the pattern. This stands in contrast to pattern-to-text matching where exact matching is solvable in linear time, like on de Bruijn graphs, but approximate matching under substitutions is solvable in subquadratic $O(n\sqrt{m})$ time, where $n$ is the text's length [Abrahamson, SIAM J. Computing 1987].