Abstract 1 Introduction 2 Preliminaries 3 Analysis 4 Conclusion and Future Work References

Improved Approximation Ratios for the Shortest Common Superstring Problem with Reverse Complements

Ryosuke Yamano ORCID Department of Computer Science, Graduate School of Information Science and Technology, The University of Tokyo, Japan
Division of Medical Data Informatics, Human Genome Center, Institute of Medical Science, The University of Tokyo, Japan
   Tetsuo Shibuya ORCID Division of Medical Data Informatics, Human Genome Center, Institute of Medical Science, The University of Tokyo, Japan
Abstract

The Shortest Common Superstring (SCS) problem asks for the shortest string that contains each of a given set of strings as a substring. Its reverse-complement variant, the Shortest Common Superstring problem with Reverse Complements (SCS-RC), naturally arises in bioinformatics applications, where for each input string, either the string itself or its reverse complement must appear as a substring of the superstring. The well-known MGREEDY algorithm for the standard SCS constructs a superstring by first computing an optimal cycle cover on the overlap graph and then concatenating the strings corresponding to the cycles, while its refined variant, TGREEDY, further improves the approximation ratio. Although the original 4- and 3-approximation bounds of these algorithms have been successively improved for the standard SCS, no such progress has been made for the reverse-complement setting. A previous study extended MGREEDY to SCS-RC with a 4-approximation guarantee and briefly suggested that extending TGREEDY to the reverse-complement setting could achieve a 3-approximation. In this work, we strengthen these results by proving that the extensions of MGREEDY and TGREEDY to the reverse-complement setting achieve 3.75- and 2.875-approximation ratios, respectively. Our analysis extends the classical proofs for the standard SCS to handle the bidirectional overlaps introduced by reverse complements. These results provide the first formal improvement of approximation guarantees for SCS-RC, with the 2.875-approximate algorithm currently representing the best known bound for this problem.

Keywords and phrases:
Shortest Common Superstring, Approximation Algorithms, DNA Sequencing
Copyright and License:
[Uncaptioned image] © Ryosuke Yamano and Tetsuo Shibuya; licensed under Creative Commons License CC-BY 4.0
2012 ACM Subject Classification:
Theory of computation Approximation algorithms analysis
Funding:
This work was supported by MEXT KAKENHI Grant Numbers 21H05052, 23H03345, and 23K18501.
Editors:
Philip Bille and Nicola Prezza

1 Introduction

The Shortest Common Superstring (SCS) problem is a classical problem in string algorithms and combinatorial optimization. Given a set S of strings, the goal is to find a shortest possible string that contains every string in S as a substring. SCS has numerous applications in various fields [7], among which one of the most prominent is DNA sequencing. A DNA molecule consists of four nucleotides (Adenine, Thymine, Guanine, and Cytosine) and is assembled from short sequence reads. This process can be viewed as an instance of the SCS problem over a quaternary alphabet. However, unlike ordinary strings, DNA sequences are double-stranded, and sequencing technologies often produce reads whose orientation is not known, i.e., which of the two DNA-duplex strands they came from [9]. Consequently, for each read, either the read itself or its reverse complement may occur in the original genome. To capture this property, the Shortest Common Superstring problem with Reverse Complements (SCS-RC) extends the classical SCS problem by requiring the superstring to contain, for each input string, either the string or its reverse complement as a substring. This extension provides a more realistic abstraction of genomic sequence reconstruction, yet its algorithmic properties and approximation guarantees have been studied far less extensively than those of the standard SCS problem.

For the standard SCS problem, Blum et al. [2] showed that the GREEDY algorithm, which repeatedly merges two distinct strings with the maximum overlap, is 4-approximate. They also introduced two variants, MGREEDY and TGREEDY, and proved that these achieve 4- and 3-approximation ratios, respectively. Many subsequent works have further improved these approximation ratios [1, 3, 14, 11, 12, 4]. Englert et al. [5] established that the MGREEDY algorithm achieves a guarantee of 67+233.396, and by combining this with the 23-approximation algorithm for the maximum asymmetric traveling salesman problem [10, 13], they obtained the currently best-known approximation ratio for SCS, 67+1492.465.

For the SCS-RC problem, Jiang et al. [8] extended the work of Blum et al. [2] to the reverse-complement setting. They proved that the extension of the MGREEDY algorithm, which we refer to as MGREEDY-RC (shown in Algorithm 1), is a 4-approximate algorithm for SCS-RC. They further noted that the TGREEDY algorithm can be similarly extended (the TGREEDY-RC algorithm shown in Algorithm 3) to achieve a 3-approximation, relying on the fact that the GREEDY-RC algorithm (shown in Algorithm 2) achieves a 12 compression ratio, which was formally proved in [6].

However, no further improvements for SCS-RC have been reported since then, leaving a substantial gap compared to the standard SCS. Our analysis narrows this gap and provides new insights into greedy algorithms under the reverse-complement setting.

Our Contributions

We first establish Theorem 1, which provides a framework analogous to that used in the standard SCS problem [4, 5].

Theorem 1.

If MGREEDY-RC is a (2+α)-approximation algorithm and there exists an algorithm that achieves a compression ratio of δ for SCS-RC, then one can construct a (2+(1δ)α)-approximation algorithm for SCS-RC. In particular, TGREEDY-RC corresponds to the case δ=12 within this general framework, which immediately yields a (2+α2)-approximation guarantee.

We extend the work of Kaplan and Shafrir [11] to the reverse-complement setting, improving the approximation guarantee of MGREEDY-RC from 4 to 3.75. The presence of reverse complements prevents the direct application of their method, since it relies on the overlap rotation lemma (stated in Lemma 13), which no longer holds when the rotated string is reverse complemented. This highlights the additional structural challenges of the SCS-RC problem compared with the standard SCS problem. Nevertheless, we manage to adapt part of their improvement by exploiting the properties of reverse complements.

Theorem 2.

MGREEDY-RC is a 3.75-approximate algorithm.

Combining Theorem 1 and Theorem 2, we immediately obtain improved guarantees for TGREEDY-RC, tightening its approximation ratio from 3 to 2.875, which currently represents the best-known bound for SCS-RC.

Theorem 3.

TGREEDY-RC is a 2.875-approximate algorithm.

2 Preliminaries

Over the alphabet Σ={a,t,g,c}, we define the complement mapping ¯:ΣΣ by

a¯=t,t¯=a,g¯=c,c¯=g.

For a string s=b1b2bnΣ, its reverse complement is defined as

s¯R=bn¯bn1¯b1¯.

In other words, s¯R is obtained by reversing s and then replacing each character biΣ with its complement bi¯. Let S={s1,,sm} be a set of strings over Σ, and define S¯R={s1¯R,,sm¯R}. Without loss of generality, we assume that SS¯R is substring-free, i.e., no string in SS¯R is a substring of another. For a string x, we use

x{x,x¯R}

to denote either x or its reverse complement. We will use this notation consistently throughout the paper. Let us formally define the SCS-RC problem:

Definition 4 (Shortest Common Superstring with Reverse Complements (SCS-RC)).
Input:

A set of strings S={s1,,sm} over an alphabet Σ.

Output:

The shortest string s such that for each siS, either si or its reverse complement si¯R appears as a substring of s.

We call a (not necessarily shortest) string that contains, for each siS, either si or its reverse complement si¯R, an approximate solution for the SCS-RC instance S.

There are two common ways to measure the quality of approximation algorithms.

Definition 5 (Length ratio and compression ratio).

Let ALG(S) denote the length of the approximate solution for the SCS-RC instance S produced by an algorithm ALG, and let OPT(S) denote the length of an optimal solution. We define the length ratio of the algorithm as ALG(S)OPT(S), and the compression ratio as SALG(S)SOPT(S), where S=siS|si|.

Since ALG(S)OPT(S), we distinguish between two notions of approximation. When δ>1, a δ-approximation refers to the length ratio, and when δ<1, it refers to the compression ratio.

For two (not necessarily distinct) strings x and y, let v be the longest string such that x=uv and y=vw for some nonempty strings u and w. We call v the overlap between x and y, and denote its length by |v|=ov(x,y). For example, if u=atat and v=tata, then ov(u,v)=3 and ov(u,u)=2. The string u is called the prefix of x with respect to y, and is denoted by pref(x,y). We define the distance from x to y as

dist(x,y)=|pref(x,y)|=|x|ov(x,y).

For a given sequence of strings x1,,xr, we define

x1,,xr=pref(x1,x2)pref(x2,x3)pref(xr1,xr)xr.

If x1,,xr are substring-free, then this string is a shortest string containing x1,,xr as substrings in this order. As observed in [2], the optimal solution of SCS-RC must have the form si1,,sim for some permutation i1,,im of {1,,m}.

The distance graph GS=(V,E,w) is the weighted complete directed graph constructed from the strings in SS¯R. The vertex set is V=SS¯R, and the edge set is E={(x,y)x,yV}. The weight of each edge (x,y)E is defined as w(x,y)=dist(x,y). The overlap graph is defined analogously, except that the weight of each edge (x,y) is given by w(x,y)=ov(x,y). Each path x1,,xr in GS corresponds to the string x1,,xr. Let C=x1,,xr,x1 be a cycle in GS. We define the weight of the cycle C as w(C)=i=1rdist(xi,xi+1), where we set xr+1=x1. A cycle cover of GS is a set of vertex-disjoint cycles such that, for each 1im, exactly one of si and si¯R is contained in the cycles. A cycle cover of GS is said to be optimal if it has the minimum total weight among all possible cycle covers. We denote an optimal cycle cover of GS by CYC(GS), and its total weight by w(CYC(GS)). Since an optimal solution to SCS-RC corresponds to a single cycle that contains exactly one of si and si¯R for each 1im, it can be viewed as a special case of a cycle cover. Therefore, we have the following inequation

w(CYC(GS))OPT(S). (1)
Algorithm 1 MGREEDY-RC.
Algorithm 2 GREEDY-RC.
Algorithm 3 TGREEDY-RC.

2.1 Greedy algorithms

Jiang et al. [8] introduced a greedy algorithm shown in Algorithm 1, which we refer to as MGREEDY-RC. Strictly speaking, they considered reversals rather than reverse complements, but their formulation and analysis can be adapted directly to our setting by interpreting their sR as s¯R. MGREEDY-RC disallows merging string pairs of the form (x,x¯R) for xx¯R, since both (distinct) x and x¯R need not be included simultaneously. As discussed in [8], the MGREEDY-RC algorithm can be viewed as constructing a cycle cover. When it merges two strings x=si1,,sih and y=sj1,,sjg, this corresponds to selecting an edge between sih and sj1 to create a new path si1,,sih,sj1,,sjg. When it merges x and y¯R, it first replaces the second path sj1,,sjg with sjg¯R,,sj1¯R, and then merges the paths to form si1,,sih,sjg¯R,,sj1¯R. When MGREEDY-RC moves a string x=si1,,sih from S to T, it closes the corresponding path into a cycle si1,,sih,si1. These operations together form a cycle cover of GS, and it has been shown that this cover is optimal.

Lemma 6 ([8]).

MGREEDY-RC creates an optimal cycle cover CYC(GS).

Fici et al. [6] proved that the GREEDY-RC algorithm, given in Algorithm 2, achieves a compression ratio of 12, and that this bound is tight for the algorithm. As in [8], they actually considered reversals rather than reverse complements, but the same analysis applies when interpreting sR as s¯R.

Lemma 7 ([6]).

GREEDY-RC achieves a compression ratio of 12.

The TGREEDY-RC algorithm, presented in Algorithm 3, is a refinement of MGREEDY-RC. Rather than concatenating the strings in T directly, it merges them by executing GREEDY-RC.

2.2 Periodicity and the overlap rotation lemma

We adopt the notation from [3, 11]. A string x is called a factor of a string s if s=xiy for some positive integer i and some (possibly empty) prefix y of x. We denote by factor(s) the shortest such string x, and define the period of s as period(s)=|factor(s)|. A semi-infinite string s is called periodic if s=xs for some nonempty string x. In this case, we denote the shortest such x by factor(s) and define period(s)=|factor(s)|.

Let x and y be strings that are either finite or periodic semi-infinite. We call x and y equivalent if factor(y) is a cyclic shift of factor(x), i.e., there exist strings e and f such that factor(x)=ef and factor(y)=fe; otherwise, we call them inequivalent. The following lemmas were proved in [2] and restated in [3].

Lemma 8 ([2]).

Let C=si1,si2,,sik,si1 be a cycle in CYC(GS). Then

factor(si1,,sik) =factor(si1,,sik,si1)
=pref(si1,si2)pref(sik1,sik)pref(sik,si1),
period(si1,,sik) =w(C).
si1,,sik,si1 =factor(si1,,sik)si1
Lemma 9 ([2]).

The strings si1,,sik,si2,,sik,si1,,sik,si1,,sik1 are all equivalent.

Lemma 10 ([2]).

Let C=si1,si2,,sih,si1 and D=sj1,sj2,,sjg,sj1 be two distinct cycles in GS. If si1,si2,,sih is equivalent to sj1,sj2,,sjg Then there exists a third cycle E with weight w(C) containing all the vertices in C and D.

Lemma 10 implies that strings taken from distinct cycles in an optimal cycle cover are inequivalent, and this property naturally extends to the reverse-complement setting.

Lemma 11.

Let C=si1,si2,,sih,si1 and D=sj1,sj2,,sjg,sj1 be two distinct cycles in CYC(GS). Then the strings e=si1,,sih and f=sj1,,sjg are inequivalent. Moreover, the pairs (e,f¯R), (e¯R,f), and (e¯R,f¯R) are also inequivalent.

The following lemma was used to gain a 4-approximate bound in [8].

Lemma 12 ([2]).

If strings x and y are inequivalent, then ov(x,y)period(x)+period(y).

Given a semi-infinite string α=x1x2, we denote the rotation α[k]=xkxk+1. Breslauer et al. [3] proved the following overlap rotation lemma.

Lemma 13 (overlap rotation lemma [3]).

Let α be a periodic semi-infinite string. There exists an integer k, such that for any finite string s that is inequivalent to α,

ov(s,α[k])period(s)+12period(α)

We denote a rotation α[k] that satisfies Lemma 13 as the critical rotation. The following lemma, originally proved in [3] and restated in [11], shows that it is possible to extract such a rotation from each cycle in CYC(GS). Property (4) relies on the fact that xD and xC are inequivalent, which follows from Property (3) together with Lemmas 9 and 11.

Lemma 14 ([3]).

Let C=si1,,sir,si1 be a cycle in CYC(GS). Then there exist a string xC and an index j such that:

  1. (1)

    The string sij+1,,sir,si1,,sij is a suffix of xC.

  2. (2)

    The string xC is contained in yC=sij,,sir,si1,,sij.

  3. (3)

    xC is equivalent to sij+1,,sir,si1,,sij.

  4. (4)

    The semi-infinite string factor(xC) is the critical rotation of factor(si1,,sir). Specifically, let xD be the string obtained by this lemma corresponding to a different cycle DCYC(GS); then ov(xD,xC)w(D)+12w(C).

3 Analysis

We begin by proving Theorem 1, which serves as the reverse-complement analogue of Theorem 3.1 in [4]. The argument follows the same ideas as the original proof.

3.1 Proof of Theorem 1

In MGREEDY-RC, we first compute the optimal cycle cover CYC(GS) and obtain the set of strings corresponding to its cycles, denoted by T (see Algorithm 1). We then observe that the optimal solution to the SCS-RC problem on this set T is at most twice as long as the optimal solution to the original instance.

Lemma 15.

OPT(T)OPT(S)+w(CYC(GS))2OPT(S).

Proof.

For each cycle C=si1,,sir,si1 in CYC(GS), we select a single representative string si1. Let SS denote the set of these representatives, one per cycle. Let u be an optimal solution to the SCS-RC problem on S. Clearly, |u|OPT(S).

For each string si1S, either si1 or its reverse complement si1¯R occurs in u. If si1 occurs, we replace one occurrence of it with

e=pref(si1,si2)pref(sir1,sir)pref(sir,si1)si1.

Otherwise, we replace si1¯R with e¯R. Note that si1 is both the prefix and the suffix of e, and similarly si1¯R is both the prefix and the suffix of e¯R. This ensures that the replacement operation is well-defined and produces a valid superstring.

This replacement increases the length of u by w(CYC(GS)), yielding an approximate solution for the SCS-RC instance T.

In practice, we do not know the optimal solution for the instance T. Instead, we can apply the given δ-approximation algorithm in terms of the compression ratio. Let ALG(T) denote the length of the solution produced by this δ-approximation algorithm on the set T. By the definition of the compression ratio, we have

δ(TOPT(T))TALG(T),

where T=xT|x| denotes the total length of strings in T. Note that T is also the length of the superstring produced by MGREEDY-RC. Hence, the (2+α)-approximation guarantee of MGREEDY implies

T(2+α)OPT(S).

Combining these inequalities, we obtain

ALG(T) (1δ)T+δOPT(T)
(1δ)(2+α)OPT(S)+2δOPT(S)
=(2+(1δ)α)OPT(S).

TGREEDY-RC corresponds to the case where we run GREEDY-RC on the set T. From Lemma 7, GREEDY-RC is a 12-approximation algorithm in terms of compression ratio, that is, δ=12.

3.2 Proof of Theorem 2

For each cycle C=si1,si2,,sir,si1 in CYC(GS), the existence of strings xC and yC satisfying the properties stated in Lemma 14 is guaranteed. We define

A={xCCCYC(GS)},A=xA|x|.

By property (1) of Lemma 14, A provides an upper bound on T.

Lemma 16.

TA.

Proof.

Consider a cycle C=si1,si2,,sir,si1 in CYC(GS), and let j be the index whose existence is guaranteed by Lemma 14. By property (1) of that lemma, we have

|sij+1,,sir,si1,,sij||xC|.

Since MGREEDY-RC greedily merges string pairs with the maximum overlap, the cycle-closing edge from sir to si1 has the smallest overlap among edges in the cycle. Hence,

ov(sir,si1)ov(sik,sik+1)for all 1k<r.

The string produced by MGREEDY-RC is si1,,sir, whose length can be computed as

|si1,,sir| =|pref(si1,si2)pref(si2,si3)pref(sir1,sir)sir|
=|pref(si1,si2)pref(si2,si3)pref(sir1,sir)pref(sir,si1)|+ov(sir,si1)
=w(C)+ov(sir,si1).

On the other hand, for the rotated sequence starting at index j+1, we have

|sij+1,,sir,si1,,sij| =|pref(sij+1,sij+2)pref(sir1,sir)pref(sir,si1)|
+|pref(si1,si2)pref(sij,sij+1)|+ov(sij,sij+1)
=w(C)+ov(sij,sij+1).

Since ov(sir,si1)ov(sij,sij+1), we conclude that

|si1,,sir||sij+1,,sir,si1,,sij|.

Summing over all cycles in CYC(GS) yields TA.

From the previous lemma, we have established that TA. Our next goal is to obtain an upper bound on A. To this end, consider the SCS-RC problem on A, and let OV(A) denote the maximal overlap in A, defined as

OV(A)=j=1k1ov(xCj,xCj+1),

where C1,,Ck are the k=|CYC(GS)| cycles in CYC(GS), ordered according to an optimal superstring xC1,,xCk for the SCS-RC instance on A.

Then, by definition, we have

A=OPT(A)+OV(A).

An upper bound on OPT(A) can be obtained in a manner similar to Lemma 15.

Lemma 17.

OPT(A)OPT(S)+w(CYC(GS)).

Proof.

Let B={yCCCYC(GS)}. By property (2) of Lemma 14, each yC contains xC, which implies OPT(A)OPT(B).

Let yC=sij,,sir,si1,,sij, and select sij as the representative of the cycle C. Let SS denote the set of these representatives over all cycles CCYC(GS).

Let u be an optimal solution of SCS-RC for S. Clearly, |u|OPT(S). For each string sijS, either sij or its reverse complement sij¯R occurs in u. If sij occurs, replace once occurence of it with the original yC; otherwise, replace sij¯R with yC¯R. This replacement increases the length of u by w(CYC(GS)), yielding an approximate solution for the SCS-RC instance B. Hence, OPT(B)OPT(S)+w(CYC(GS)). Together with OPT(A)OPT(B), we obtain OPT(A)OPT(S)+w(CYC(GS)).

For each cycle C=si1,si2,,sir,si1 in CYC(GS), we can consider its reverse complement, C¯R=si1¯R,sir¯R,,si2¯R,si1¯R. For this C¯R, there exists a string xC¯R that satisfies the properties stated in Lemma 14. However, since xC¯R and xC¯R may differ, we cannot directly derive the upper bound OV(A)1.5w(CYC(GS)) from Lemmas 13 and 14.

Therefore, when the reverse complement xC¯R appears in the optimal solution, we must apply Lemma 12 instead of Lemma 13. The key observation is that, by also considering the reverse complement of the entire optimal superstring, the proportion of such strings can be limited to at most half.

Lemma 18.

OV(A)1.75w(CYC(GS)).

Proof.

Let C1,,Ck be the k=|CYC(GS)| cycles in CYC(GS), ordered according to an optimal solution for the SCS-RC instance on A. Let v=xC1,,xCk denote this optimal superstring. Recall that for any ij, the strings xCi and xCj are inequivalent, as discussed in Section 2.2. Then,

OV(A) =j=1k1ov(xCj,xCj+1)
j=2k{w(Cj1)+0.5w(Cj),if xCj=xCj(by Lemma 13),w(Cj1)+w(Cj),if xCj=xCj¯R(by Lemma 12).

Rearranging the terms gives

OV(A)j=1k{1.5w(Cj),if xCj=xCj,2w(Cj),if xCj=xCj¯R.

Next, consider the reverse complement of the optimal solution, v¯R=xCk¯R,,xC1¯R, which is also an optimal superstring for the same instance. In this reversed solution, every occurrence of xCj is replaced by xCj¯R, and vice versa. Hence, we also have

OV(A)j=1k{2w(Cj),if xCj=xCj,1.5w(Cj),if xCj=xCj¯R.

By adding the two inequalities and dividing by two, we obtain

2OV(A)j=1k3.5w(Cj),that is,OV(A)1.75w(CYC(GS)).

From Lemmas 17 and 18, we obtain the following upper bound on A:

A =OPT(A)+OV(A)
OPT(S)+w(CYC(GS))+1.75w(CYC(GS))
=OPT(S)+2.75w(CYC(GS)).

Using Lemma 16, we then have

TAOPT(S)+2.75w(CYC(GS))3.75OPT(S),

which completes the proof of Theorem 2.

4 Conclusion and Future Work

We have improved the approximation guarantees of MGREEDY-RC and TGREEDY-RC for the SCS-RC problem by leveraging the overlap rotation lemma and certain properties of reverse complements. The remaining gaps compared to the standard SCS problem are mainly in two aspects:

  1. (1)

    The approximation guarantee of MGREEDY-RC.

  2. (2)

    The compression ratio.

For the first aspect, we improved the approximation guarantee from 4 to 3.75. However, for the standard SCS problem, the best known ratio of the corresponding MGREEDY algorithm is 67+233.396 [5], so closing this gap remains an open research direction.

For the second aspect, we used the 12-approximation compression ratio algorithm in GREEDY-RC. In the case of the standard SCS, the problem can be reduced to the maximum asymmetric traveling salesman problem (MAX-ATSP), which is known to have a 23-approximation algorithm [10, 13]. However, for the SCS-RC problem, we must consider clusters containing two vertices each, which prevents the direct application of approximation algorithms for MAX-ATSP. Another research direction is to find a suitable reduction related to the MAX-ATSP problem, or to consider an entirely different approach to improve the compression ratio.

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