kuniga.me > NP-Incompleteness > De Bruijn Graphs and Sequences

26 Dec 2018

Nicolaas Govert de Bruijn was a Dutch mathematician, born in the Hague and taught University of Amsterdam and Technical University Eindhoven.

Irving John Good was a British mathematician who worked with Alan Turing, born to a Polish Jewish family in London. De Bruijn and Good independently developed a class of graphs known as *de Bruijn graphs*, which we’ll explore in this post.

A **de Bruijn graph** [1] is a directed graph defined over a dimension n and a set S of m symbols. The set of vertices in this graph corresponds to the m^n possible sequences of symbols with length n (symbols can be repeated).

There’s a directed edge from vertex u to v if the sequence from v can be obtained from u by removing u’s first element and then appending a symbol at the end. For example, if S = {A, B, C, D}, n = 3 and u = ABC, then there’s an edge from ABC to BC*, that is, BCA, BCB, BCC and BCD.

We can derive some basic properties for de Bruijn graphs.

*1) Every vertex has exactly m incoming and m outgoing edges.*

We saw from the example above that ABC had edges to any vertex BC*, where * is any of the m symbols in S. Conversely, any sequence in the form *AB can be transformed into ABC, by dropping the first symbol and appending ‘C’.

*2) Every de Bruijn graph is Eulerian.*

In our last post we discussed about Eulerian graphs and learned that a necessary and sufficient condition for a directed graph to have an Eulerian cycle is that all the vertices in the graph have the same in-degree and out-degree and that it’s strongly connected. The first condition is clearly satisfied given the Property 1) above.

To see that a de Bruijn graph is strongly connected, we just need to note that it’s possible to convert any sequence into another by removing the first character and replacing the last with the appropriate one in at most n steps. For example, given the string ABC, we can convert it to BDD by doing ABC -> BCB -> CBD -> BDD. Since each such step corresponds to traversing an edge in the de Bruijn graph, we can see it’s possible to go from any vertex to another, making the graph strongly connected.

*3) A de Bruijn graph over the set of symbols S and dimension n is the line graph of the de Bruijn graph over set S and dimension n - 1*

A **line graph** of a given graph G has vertices corresponding to edges in G, and there are edges between two vertices if the corresponding edges in G share a vertex. More formally, let G = (V, E) be an undirected graph. The line graph of G, denoted by L(G) has a set of vertex V’ corresponding to E. Let u’, v’ be two vertices from V’, corresponding to edges e1 and e2 in E. There’s an edge between u’ and v’ if e1 and e2 have one vertex in common.

It’s possible to generalize this to directed graphs by changing the definition of edges slightly: let u’, v’ be two vertices from V’, corresponding to the directed edges e1 = (a, b) and e2 = (c, d) in E. Then there’s a directed edge from u’ to v’ if and only if b = c.

We can gain an intuition on Property 3 by looking at an example with set S = {0, 1} and constructing a de Bruijn graph with n = 2 from one with n = 1. In Figure 1, the vertices from n = 2 are the labeled edges of n = 1. The edges in n = 2 correspond to the directed paths of length 2 in n = 1. We highlighted in red one of such paths. In n = 1, the path is given by (0, 1) and (1, 1), which became (01, 11) in n = 2.

*4) Every de Bruijn graph is Hamiltonian*

This follows from Properties 2 and 3. We claim that an Eulerian cycle in a De Bruijn graph in dimension n is a Hamiltonian path in dimension n + 1. That’s because we visit every edge exactly once and each edge corresponds to a vertex in the graph in dimension n + 1. Given two consecutive edges in the Eulerian cycle in dimension n, (u, v) and (v, w), from Property 3 we know that there’s an edge from the corresponding vertex (u, v)’ to vertex (v, w)’ in dimension n + 1.

The de Bruijn sequence of dimension n on a set of symbols S, denoted B(S, n), is a cyclic sequence in which every possible sequences of length n appears as substring. The length of such sequence is |S|^n.

Since |S|^n is also the number of distinct sequences of length n, we can conclude that this sequence is the shortest possible. To see why, let B be a de Bruijn sequence. We can assign an index p to each sequence s of length n based on where it appears in B such that the substring B[p, p + n - 1] represents s. Since each of the |S|^n sequences are distinct, they cannot have the same index p. Hence, there must be at least |S|^n indexes, and thus B must be at least that long.

It’s possible to construct a de Bruijn sequence B(S, n) from the Hamiltonian path of a de Bruijn graph over S and dimension n. Two adjacent nodes in the Hamiltonian path share n-1 symbols, so if we start with a vertex v, each new vertex in the path only adds one symbol. It would have a total of n + (|S|^n - 1), but since the last n-1 symbols of the sequence overlap with the beginning when we wrap in a cycle, the cyclic sequence has length |S|^n.

Note that we can construct an Hamiltonian cycle for a de Bruijn graph in polynomial time because it’s equivalent to the Eulerian path in one dimension below. Hence we have a polynomial time algorithm to construct the de Bruijn sequence.

**Cracking Locks**

A de Bruijn sequence can be used to brute-force a lock without an enter key, that is, one that opens whenever the last n digits tried are correct. A naive brute force would need to try all |S|^n typing n digits every time, for a total of |S|^n. Using a de Bruijn sequence we would make use of the overlap between trials, and only need to type |S|^n digits in total.

**Finding the Least Significant Bit**

The other interesting application mentioned in [2] is to determine the index of the least significant bit in an unsigned int (32-bits). The code provided is given by:

Let’s understand what the code above is doing. For now, let’s assume v > 0 and we’ll handle `v = 0`

as a special case later.

In the code above, `(v & -v)`

has the effect of “isolating” the least significant bit. Since v is unsigned, -v is its two’s complement, that is, we complement the digits of v `(~v)`

and add one. Let p be the position of the least significant digit in v. The bits in positions lower than p will be 1 in `~v`

, and in position p it’s a 0. When incremented by 1, they’ll turn into 1 in position p and 0 in the lower positions. In the positions higher than `p`

, `v`

and `-v`

will be have complementary bits. When doing a bitwise AND, the only position where both operands have 1 is p, hence it will be the number `(1 << p)`

(or `2^p`

).

Then we multiply the result above by `0x077CB531U`

which is the de Bruijn sequence B({0, 1}, 5) in hexadecimal. In binary this is 00000111011111001011010100110001, which is a 32-bit number. Because `v & -v`

is a power of 2 (`2^p`

), multiplying a number by it is the same as bit-shifting it to the left p positions. Then we shift it to the right by 27 positions, which has the effect of capturing the 5 most significant bits from the resulting multiplication. If we treat the number as a string of characters (note that most significant bits are the first characters), the left shift followed by the right shift is equivalent to selecting a “substring” from position `p`

to `p+5`

.

For example, if `p = 13`

, a left shift on 00000111011111001011010100110001 would result in 10010110101001100010000000000000. Then a right shift of 27, would pick the 5 leftmost bits, 10010. If we treat 00000111011111001011010100110001 as a string, 10010 shows up as a substring 0000011101111**10010**11010100110001 in positions [13, 17].

Since this is a de Bruijn sequence for `n = 5`

, every substring of length 5 corresponds to a unique 5-bit number and conversely every 5-bit number is present in this sequence. Now we just need to keep a map from the 5-bit number we obtained via the bit manipulation to the actual number we wanted, which we store in `MultiplyDeBruijnBitPosition`

. Since 10010 is 18, we’ll have an entry `MultiplyDeBruijnBitPosition[18] = 13`

.

Finally, for the special case where `v = 0`

, we have that `v & -v`

is 0 and the algorithm will return 0.

**Assembling DNA Fragments**

In [3] Compeau and Pevzner proposed a method to assemble fragments of DNA into its original form. The problem can be modeled as the *k-universal circular string problem*.

Definition: Consider a list of sequences s_1, s_2, …, s_n, each of which having the same size k, having the property that s_i’ s suffix and s_i+1 ‘ s prefix overlap in k-1 positions. That is, the last k-1 characters in s_i are the same as the first k-1 characters in s_i+1. We are given the sequences in no particular order. The objective is to find a composed string S which is the result of the overlap of s_1, s_2, …, s_n in order.

This problem can be modeled as a de Bruijn graph where each sequence is associated with a vertex. If sequence s_i’s suffix and s_j’s prefix overlap in k-1 positions, we add a directed edge from vertex s_i to s_j. We then find an Hamiltonian path in the de Bruijn graph and the order in which the vertices are visited will give us the desired string.

One variant to the de Bruijn sequence problem is to, instead of finding a universal sequence containing all possible sequences of length n, find one containing all the permutations of the symbols in S. Instead of the |S|^ n sequences as input, we’ll have |S|! sequences. This is know as the **Super-permutation problem**.

For example, for S = {1, 2}, it want to find a sequence containing: 12 and 21. The sequence 121 is a possible solution. For S = {1, 2, 3}, we have now 123, 132, 213, 231, 312 and 321. The shortest 123121321. John Carlos Baez tweets about this problem in [4]. Finding the shortest sequence that includes all permutations is an open problem!

We know optimal solution for n up to 5. The best known lower bound for this problem is `n! + (n−1)! + (n−2)! + n − 3`

while the upper bound is `n! + (n−1)! + (n−2)! + (n−3)! + n − 3`

[5].

In this post I was mainly interested in learning more about de Bruijn graphs after reading about them in Bioinformatics Algorithms by Compeau and Pevzner [3]. I ended up learning about de Bruijn sequences and realized that the problem was similar to one I read about recently on John’s Twitter. It was a nice coincidence.