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1.
A contig assembly program based on sensitive detection of fragment overlaps.   总被引:23,自引:0,他引:23  
X Huang 《Genomics》1992,14(1):18-25
An effective computer program for assembling DNA fragments, the contig assembly program (CAP), has been developed. In the CAP program, a filter is used to eliminate quickly fragment pairs that could not possibly overlap, a dynamic programming algorithm is applied to compute the maximal-scoring overlapping alignment between each remaining pair of fragments, and a simple greedy approach is employed to assemble fragments in order of alignment scores. To identify the true fragment overlaps, the dynamic programming algorithm uses specially chosen sets of alignment parameters to tolerate sequencing errors and to penalize "mutational" changes between different copies of a repetitive sequence. The performance tests of the program on fragment data from genomic sequencing projects produced satisfactory results. The CAP program is efficient in computer time and memory; it took about 4 h to assemble a set of 1015 fragments into long contigs on a Sun workstation.  相似文献   

2.
Fast, optimal alignment of three sequences using linear gap costs   总被引:2,自引:0,他引:2  
Alignment algorithms can be used to infer a relationship between sequences when the true relationship is unknown. Simple alignment algorithms use a cost function that gives a fixed cost to each possible point mutation-mismatch, deletion, insertion. These algorithms tend to find optimal alignments that have many small gaps. It is more biologically plausible to have fewer longer gaps rather than many small gaps in an alignment. To address this issue, linear gap cost algorithms are in common use for aligning biological sequence data. More reliable inferences are obtained by aligning more than two sequences at a time. The obvious dynamic programming algorithm for optimally aligning k sequences of length n runs in O(n(k)) time. This is impractical if k>/=3 and n is of any reasonable length. Thus, for this problem there are many heuristics for aligning k sequences, however, they are not guaranteed to find an optimal alignment. In this paper, we present a new algorithm guaranteed to find the optimal alignment for three sequences using linear gap costs. This gives the same results as the dynamic programming algorithm for three sequences, but typically does so much more quickly. It is particularly fast when the (three-way) edit distance is small. Our algorithm uses a speed-up technique based on Ukkonen's greedy algorithm (Ukkonen, 1983) which he presented for two sequences and simple costs.  相似文献   

3.
Protein sequence alignment has become an essential task in modern molecular biology research. A number of alignment techniques have been documented in literature and their corresponding tools are made available as freeware and commercial software. The choice and use of these tools for sequence alignment through the complete interpretation of alignment results is often considered non-trivial by end-users with limited skill in Bioinformatics algorithm development. Here, we discuss the comparison of sequence alignment techniques based on dynamic programming (N-W, S-W) and heuristics (LFASTA, BL2SEQ) for four sets of sequence data towards an educational purpose. The analysis suggests that heuristics based methods are faster than dynamic programming methods in alignment speed.  相似文献   

4.
We describe an exhaustive and greedy algorithm for improving the accuracy of multiple sequence alignment. A simple progressive alignment approach is employed to provide initial alignments. The initial alignment is then iteratively optimized against an objective function. For any working alignment, the optimization involves three operations: insertions, deletions and shuffles of gaps. The optimization is exhaustive since the algorithm applies the above operations to all eligible positions of an alignment. It is also greedy since only the operation that gives the best improving objective score will be accepted. The algorithms have been implemented in the EGMA (Exhaustive and Greedy Multiple Alignment) package using Java programming language, and have been evaluated using the BAliBASE benchmark alignment database. Although EGMA is not guaranteed to produce globally optimized alignment, the tests indicate that EGMA is able to build alignments with high quality consistently, compared with other commonly used iterative and non-iterative alignment programs. It is also useful for refining multiple alignments obtained by other methods.  相似文献   

5.
基于动态规划的快速序列比对算法   总被引:3,自引:0,他引:3  
序列比对算法是生物信息学中重要的研究方向之一,而动态规划法是序列比对算法中最有效最基本的方法.由于原有的基本动态规划方法时间和空间复杂度大,不适合实际的生物序列比对,因此本文在分析介绍几种相关动态规划算法的基础上,提出了一种基于动态规划的快速序列比对算法UKK_FA.实验结果表明,该算法有效地降低了时间复杂度,具有一定的实用性。  相似文献   

6.
Recomputation of the previously evaluated similarity results between biological sequences becomes inevitable when researchers realize errors in their sequenced data or when the researchers have to compare nearly similar sequences, e.g., in a family of proteins. We present an efficient scheme for updating local sequence alignments with an affine gap model. In principle, using the previous matching result between two amino acid sequences, we perform a forward-backward alignment to generate heuristic searching bands which are bounded by a set of suboptimal paths. Given a correctly updated sequence, we initially predict a new score of the alignment path for each contour to select the best candidates among them. Then, we run the Smith-Waterman algorithm in this confined space. Furthermore, our heuristic alignment for an updated sequence shows that it can be further accelerated by using reusable dynamic programming (rDP), our prior work. In this study, we successfully validate "relative node tolerance bound” (RNTB) in the pruned searching space. Furthermore, we improve the computational performance by quantifying the successful RNTB tolerance probability and switch to rDP on perturbation-resilient columns only. In our searching space derived by a threshold value of 90 percent of the optimal alignment score, we find that 98.3 percent of contours contain correctly updated paths. We also find that our method consumes only 25.36 percent of the runtime cost of sparse dynamic programming (sDP) method, and to only 2.55 percent of that of a normal dynamic programming with the Smith-Waterman algorithm.  相似文献   

7.
一个新的核酸序列比对算法及其在序列全局比对中的应用   总被引:1,自引:0,他引:1  
目前在序列比对中所广泛使用的动态规划算法,虽然能达到最优比对结果,但却由于具有高计算复杂度O(N_2)而极大地降低了计算效率。将多阶段动态规划决策算法用于两两序列比对并用Visual BASIC编程实现,结果发现该新算法在将计算复杂度减小到O(N)的同时,也能够获得较为理想的计算精度,预期将在序列全局比对中起重要作用。  相似文献   

8.

Background  

Accurate sequence alignment is required in many bioinformatics applications but, when sequence similarity is low, it is difficult to obtain accurate alignments based on sequence similarity alone. The accuracy improves when the structures are available, but current structure-based sequence alignment procedures still mis-align substantial numbers of residues. In order to correct such errors, we previously explored the possibility of replacing the residue-based dynamic programming algorithm in structure alignment procedures with the Seed Extension algorithm, which does not use a gap penalty. Here, we describe a new procedure called RSE (Refinement with Seed Extension) that iteratively refines a structure-based sequence alignment.  相似文献   

9.
Multiple sequence alignment (MSA) is one of the most fundamental problems in computational molecular biology. The running time of the best known scheme for finding an optimal alignment, based on dynamic programming, increases exponentially with the number of input sequences. Hence, many heuristics were suggested for the problem. We consider a version of the MSA problem where the goal is to find an optimal alignment in which matches are restricted to positions in predefined matching segments. We present several techniques for making the dynamic programming algorithm more efficient, while still finding an optimal solution under these restrictions. We prove that it suffices to find an optimal alignment of the predefined sequence segments, rather than single letters, thereby reducing the input size and thus improving the running time. We also identify "shortcuts" that expedite the dynamic programming scheme. Empirical study shows that, taken together, these observations lead to an improved running time over the basic dynamic programming algorithm by 4 to 12 orders of magnitude, while still obtaining an optimal solution. Under the additional assumption that matches between segments are transitive, we further improve the running time for finding the optimal solution by restricting the search space of the dynamic programming algorithm  相似文献   

10.
Structural comparison of multiple-chain protein complexes is essential in many studies of protein–protein interactions. We develop a new algorithm, MM-align, for sequence-independent alignment of protein complex structures. The algorithm is built on a heuristic iteration of a modified Needleman–Wunsch dynamic programming (DP) algorithm, with the alignment score specified by the inter-complex residue distances. The multiple chains in each complex are first joined, in every possible order, and then simultaneously aligned with cross-chain alignments prevented. The alignments of interface residues are enhanced by an interface-specific weighting factor. MM-align is tested on a large-scale benchmark set of 205 × 3897 non-homologous multiple-chain complex pairs. Compared with a naïve extension of the monomer alignment program of TM-align, the alignment accuracy of MM-align is significantly higher as judged by the average TM-score of the physically-aligned residues. MM-align is about two times faster than TM-align because of omitting the cross-alignment zone of the DP matrix. It also shows that the enhanced alignment of the interfaces helps in identifying biologically relevant protein complex pairs.  相似文献   

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