Global Alignment of Protein Sequences with Position-Specific Scoring Matrices.

蛋白质序列与位置特异性评分矩阵的全局比对。

• 批准号: 8558118
• 负责人: John Spouge
• 金额: $ 6.51万
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8558118
• 关键词: Affect; Algorithms; Amino Acid Sequence; Amino Acid Sequence Databases; Biotechnology; Code; Databases; Evolution; Gene Mutation; Goals; Methods; Peptide Sequence Determination; Positioning Attribute; Protein Databases; Protein Structure Initiative; Proteins; Retrieval; Speed; Structure; Tertiary Protein Structure; heuristics; improved; markov model; novel; programs; simulation; tool

NCBI currently uses the local alignment tool "rps-BLAST" to search the CDD. Local alignment tools are inherently inappropriate for CDD retrieval, because complete domains (by definition) are the units conserved in evolution. Thus, retrieval should compare complete domains to protein subsequences, which is "semi-global" alignment. Accordingly, we developed a semi-global alignment algorithm and a novel statistical approximation that discovers whole protein domains within a query protein sequence, thereby giving clues as to the function of novel protein sequences. Simulations show that the approximation is much better than the p-value approximations in other tools like HMMer and rps-BLAST, making GLOBAL a promising candidate for an iterative search tool in protein sequence databases. Dr Sergey Sheetlin implemented our method as a dynamic-programming algorithm in a program called "GLOBAL". Dr Kann analyzed the retrieval efficacy of several competitive methods, including HMMer, an implementation of Hidden Markov models (HMMs), and shown that the retrieval efficacies are in the order: HMMer (in global mode) - about the same as GLOBAL, GLOBAL - better than rps-BLAST. GLOBAL is in fact a degenerate HMM. While retaining HMM retrieval efficacies, GLOBAL is simple enough to be accelerated by the same heuristics used in local alignment methods like BLAST. Accordingly, Dr. Carroll accelerated GLOBAL using the BLAST word-heuristic, speeding it by about an order of magnitude, making its speed competitive with other domain-retrieval tools. He has incorporated the resulting code in the NCBI CoreTools.

NCBI目前使用本地比对工具“rp - blast”来搜索CDD。局部对齐工具本质上不适合CDD检索，因为完整域（根据定义）是进化中保守的单元。因此，检索应该将完整结构域与蛋白质子序列进行比较，这是“半全局”比对。因此，我们开发了一种半全局比对算法和一种新的统计近似方法，可以在查询的蛋白质序列中发现整个蛋白质结构域，从而为新蛋白质序列的功能提供线索。仿真结果表明，该方法比HMMer和rpps - blast等其他工具的p值逼近效果要好得多，使GLOBAL成为蛋白质序列数据库迭代搜索工具的一个有希望的候选工具。Sergey Sheetlin博士在一个名为“GLOBAL”的程序中将我们的方法作为动态规划算法实现。Kann博士分析了几种竞争方法的检索效率，包括hmm，一种隐马尔可夫模型（hmm）的实现，并表明检索效率的顺序是：hmm（在全局模式下）-与global， global大致相同-比rp - blast更好。GLOBAL实际上是一个简并HMM。在保留HMM检索效率的同时，GLOBAL足够简单，可以使用与BLAST等局部对齐方法相同的启发式方法来加速。因此，Carroll博士使用BLAST单词启发式加速了GLOBAL，将其速度提高了大约一个数量级，使其速度与其他领域检索工具相媲美。他已经将结果代码合并到NCBI CoreTools中。