Bit-parallel sequence-to-graph alignment

Motivation: Graphs are commonly used to represent sets of sequences. Either edges or nodes can be labeled by sequences, so that each path in the graph spells a concatenated sequence. Examples include graphs to represent genome assemblies, such as string graphs and de Bruijn graphs, and graphs to represent a pan-genome and hence the genetic variation present in a population. Being able to align sequencing reads to such graphs is a key step for many analyses and its applications include genome assembly, read error correction and variant calling with respect to a variation graph. Results: We generalize two linear sequence-to-sequence algorithms to graphs: the Shift-And algorithm for exact matching and Myers' bitvector algorithm for semi-global alignment. These linear algorithms are both based on processing w sequence characters with a constant number of operations, where w is the word size of the machine (commonly 64), and achieve a speedup of up to w over naive algorithms. For a graph with vertical bar V vertical bar nodes and vertical bar E vertical bar edges and a sequence of length m, our bitvector-based graph alignment algorithm reaches a worst case runtime of O(vertical bar V vertical bar+(sic)m/w(sic)vertical bar E vertical bar logw) for acyclic graphs and O(vertical bar V vertical bar+m vertical bar E vertical bar logw) for arbitrary cyclic graphs. We apply it to five different types of graphs and observe a speedup between 3-fold and 20-fold compared with a previous (asymptotically optimal) alignment algorithm.Peer reviewe