A fast algorithm for the constrained multiple sequence alignment problem

Given n strings S1, S2, ..., Sn, and a pattern string P, the constrained multiple sequence alignment (CMSA) problem is to find an optimal multiple alignment of S1, S2, ..., Sn such that the alignment contains P, i.e. in the alignment matrix there exists a sequence of columns each entirely composed of symbol P[k] for every k, where P[k] is the kth symbol in P, 1 ≤ k ≤ |P|, and in the sequence, a column containing P[i] appears before the column containing P[j] for all i,j, i < j. The problem is motivated from the problem of comparing multiple sequences that share a common structure, or sequence pattern. There are O(2ns1s2...snr)-time dynamic programming algorithms for the problem, where s1,s2, ...,sn and r are, respectively, the lengths of the input strings and the pattern string. Feasibility of these algorithms in practice is limited when the number of sequences is large, or the sequences are long because of the impractically long time required by these algorithms. We present a new algorithm with worst-case time complexity also O(2ns1s2...snr), but the algorithm avoids redundant computations in existing dynamic programming solutions. Experiments on both randomly generated strings and real data show that this algorithm is much faster than the existing algorithms. We present an analysis that explains the speed-up obtained in our experiments by our algorithm over the naive dynamic programming algorithm for constrained multiple sequence alignment of protein sequences. The speed-up is more significant when pattern is long, or n is large. For example in the case of constrained pairwise sequence alignment (the CMSA problem with n=2) when the pattern is sufficiently long for strings S1 and S2, the asymptotic time complexity is observed to be O(s1s2) instead of O(s1s2r). Main ideas in our algorithm can also be used in other constrained sequence alignment problems

Inference with Constrained Hidden Markov Models in PRISM

A Hidden Markov Model (HMM) is a common statistical model which is widely used for analysis of biological sequence data and other sequential phenomena. In the present paper we show how HMMs can be extended with side-constraints and present constraint solving techniques for efficient inference. Defining HMMs with side-constraints in Constraint Logic Programming have advantages in terms of more compact expression and pruning opportunities during inference. We present a PRISM-based framework for extending HMMs with side-constraints and show how well-known constraints such as cardinality and all different are integrated. We experimentally validate our approach on the biologically motivated problem of global pairwise alignment

MAVID: Constrained ancestral alignment of multiple sequences

We describe a new global multiple alignment program capable of aligning a large number of genomic regions. Our progressive alignment approach incorporates the following ideas: maximum-likelihood inference of ancestral sequences, automatic guide-tree construction, protein based anchoring of ab-initio gene predictions, and constraints derived from a global homology map of the sequences. We have implemented these ideas in the MAVID program, which is able to accurately align multiple genomic regions up to megabases long. MAVID is able to effectively align divergent sequences, as well as incomplete unfinished sequences. We demonstrate the capabilities of the program on the benchmark CFTR region which consists of 1.8Mb of human sequence and 20 orthologous regions in marsupials, birds, fish, and mammals. Finally, we describe two large MAVID alignments: an alignment of all the available HIV genomes and a multiple alignment of the entire human, mouse and rat genomes

Algorithms for the Problems of Length-Constrained Heaviest Segments

We present algorithms for length-constrained maximum sum segment and maximum density segment problems, in particular, and the problem of finding length-constrained heaviest segments, in general, for a sequence of real numbers. Given a sequence of n real numbers and two real parameters L and U (L <= U), the maximum sum segment problem is to find a consecutive subsequence, called a segment, of length at least L and at most U such that the sum of the numbers in the subsequence is maximum. The maximum density segment problem is to find a segment of length at least L and at most U such that the density of the numbers in the subsequence is the maximum. For the first problem with non-uniform width there is an algorithm with time and space complexities in O(n). We present an algorithm with time complexity in O(n) and space complexity in O(U). For the second problem with non-uniform width there is a combinatorial solution with time complexity in O(n) and space complexity in O(U). We present a simple geometric algorithm with the same time and space complexities. We extend our algorithms to respectively solve the length-constrained k maximum sum segments problem in O(n+k) time and O(max{U, k}) space, and the length-constrained $k$ maximum density segments problem in O(n min{k, U-L}) time and O(U+k) space. We present extensions of our algorithms to find all the length-constrained segments having user specified sum and density in O(n+m) and O(nlog (U-L)+m) times respectively, where m is the number of output. Previously, there was no known algorithm with non-trivial result for these problems. We indicate the extensions of our algorithms to higher dimensions. All the algorithms can be extended in a straight forward way to solve the problems with non-uniform width and non-uniform weight.Comment: 21 pages, 12 figure

An Efficient Dynamic Programming Algorithm for the Generalized LCS Problem with Multiple Substring Exclusion Constrains

In this paper, we consider a generalized longest common subsequence problem with multiple substring exclusion constrains. For the two input sequences $X$ and $Y$ of lengths $n$ and $m$, and a set of $d$ constrains $P=\{P_1,...,P_d\}$ of total length $r$, the problem is to find a common subsequence $Z$ of $X$ and $Y$ excluding each of constrain string in $P$ as a substring and the length of $Z$ is maximized. The problem was declared to be NP-hard\cite{1}, but we finally found that this is not true. A new dynamic programming solution for this problem is presented in this paper. The correctness of the new algorithm is proved. The time complexity of our algorithm is $O(nmr)$.Comment: arXiv admin note: substantial text overlap with arXiv:1301.718

Stochastic Block Coordinate Frank-Wolfe Algorithm for Large-Scale Biological Network Alignment

With increasingly "big" data available in biomedical research, deriving accurate and reproducible biology knowledge from such big data imposes enormous computational challenges. In this paper, motivated by recently developed stochastic block coordinate algorithms, we propose a highly scalable randomized block coordinate Frank-Wolfe algorithm for convex optimization with general compact convex constraints, which has diverse applications in analyzing biomedical data for better understanding cellular and disease mechanisms. We focus on implementing the derived stochastic block coordinate algorithm to align protein-protein interaction networks for identifying conserved functional pathways based on the IsoRank framework. Our derived stochastic block coordinate Frank-Wolfe (SBCFW) algorithm has the convergence guarantee and naturally leads to the decreased computational cost (time and space) for each iteration. Our experiments for querying conserved functional protein complexes in yeast networks confirm the effectiveness of this technique for analyzing large-scale biological networks