Improvements And Extensions To The Blast Algorithms

今年的工作重点是分析 最小描述长度（MDL）原则 用于PSI-BLAST的伪计数。 简而言之，PSI-BLAST估计 氨基酸出现在比对位置的概率 通过将观察到的氨基酸计数与数据依赖性假计数相结合。 伪计数的数量在过去是凭经验选择的。 我们已经使用MDL原理从理论推导出 应该使用的伪计数。 该理论表明，对于 多重比对中序列的实际数量n， 的伪计数实际上应该与n无关。 但 理论还表明，伪计数的数量应该取决于 对齐列的组成，具有更高的约束 接收较少伪计数的列。 这会增加 蛋白质谱列之间得分的“对比”。 我们有 实现了指定伪计数的新过程，并发现 它提高了PSI-BLAST检索的准确性， 重要程度。 默认情况下， PSI-BLAST，描述这项工作的手稿正在编写中。

Work this year has focused on an analysis of the application of the minimum description length (MDL) principle to the specification of pseudocounts for use with PSI-BLAST. In brief, PSI-BLAST estimates the probabilities of amino acids occurring in an alignment position by combining observed amino acid counts with data-dependent pseudocounts. The number of pseudocounts has in the past been chosen empirically. We have used the MDL principle to derive from theory the number of pseudocounts that should be employed. The theory suggests that for a realistic number n of sequences in a multiple alignment, the number of pseudocounts should be practically independent of n. However, the theory also suggests that the number of pseudocounts should depend on the composition of alignment columns, with more highly constrained columns receiving fewer pseudocounts. This has the effect of increasing the "contrast" in scores between protein profile columns. We have implemented a new procedure for specifying pseudocounts, and found that it improves PSI-BLAST retrieval accuracy to a statistically significant extent. This new procedure is now used by default by PSI-BLAST, and a manuscript describing the work is in preparation.