The artwork on the cover is by Hillary Fayle, and it alludes to a number of concepts related to the book:

• The connections between the leaf and the thread stand for the tight interaction between wet-lab experiments and computer science that characterizes current molecular biology. As Donald Knuth put it, "biology is so digital."
• The tension of the thread, and the geometrical pattern it creates, represent the rigor of combinatorial proofs and the creative process of algorithm design. The knitting itself required an "algorithm" to be created. As a result of the tension from the thread, the leaf bends slightly – a metaphor of the fact that some biological details are abstracted away in the process of formulating combinatorial problems.
• The geometrical pattern of the thread is based on repetition, and the book studies a number of exact repetitions in strings.
• The leaf comes from a tree, and some trees are known to have very large genomes, motivating the efficient algorithms described in the book. The thread is a string, and genomes are also strings. In particular, the thread fills a gap in the leaf, a reference to the gap filling problem formulated in the assembly chapter. The algorithm we describe for solving this problem uses a number of combinatorial tools presented in the book, like assembly graphs, the Burrows-Wheeler transform, dynamic programming, and the Bellman-Ford method. The solution to the gap filling problem is a path in the assembly graph: path covers and flows are the central topic of the transcriptomics chapter.
• The relationship between weaving and algorithm design goes back at least to the programmable mechanical looms of the 18th century, and the parallel between textiles and language (and genomes are a specific type of text) goes back at the least to the creation myths of the Dogon mythology. Some works of art, for example those by Anni Albers, reflect on the combinational and structural properties of textiles, notions that resonate with combinatorics.
• A geometrical interplay between a thread and the leaves and branches of trees appears also in the ceiling of the Sala delle Asse by Leonardo da Vinci.