Improvements and Extensions to the BLAST Algorithms

PSI-BLAST搜索中偶尔出现的问题是 进化的序列概况的“腐败”， 在PSI-BLAST多重分析中包含非同源序列 对齐。 在过去的几年里，腐败已经大大 通过PSI-BLAST统计量的改进， 最重要的是通过考虑非标准序列 混合物. 然而，最近有人观察到， PSI-BLAST配置文件可能会损坏的文献 通过“同源过度延伸”，一个问题， 通过改进统计数据来补救。 简而言之，这个问题 当一个“真实”对齐的边界 计算错误，产生的对齐时间比它长 应该的 如果这样的对齐延伸到 在数据库中广泛出现的主题序列， 随后的PSI-BLAST迭代，以类似棘轮的方式， 来包括完整的域，即使它 不存在于查询序列中。 问题是由于没有 错误的统计数据，错误的排列。 一个解决方案 这个问题已经在文献中提出，但我们 采取了我们认为更好的补救措施， 通过一定数量的位来修整每一端的对准。 这种方法的初步测试是有希望的， 该方法的开发仍在继续。 没有出版物 但结果。

A problem that occasionally arises in PSI-BLAST searches is the "corruption" of the evolving sequence profile through the inclusion of non-homologous sequences in the PSI-BLAST multiple alignment. In previous years, corruption has been greatly reduced through the improvement of PSI-BLAST statistics, most importantly by accounting for non-standard sequence composition. Recently, however, it has been observed in the literature that PSI-BLAST profiles may become corrupted through "homologous over-extension", a problem that can not be remedied by improved statistics. In brief, this problem arises when the boundaries of an otherwise "true" alignment are miscalculated, yielding the alignment longer than it should be. If such an alignment extends into a domain in the subject sequence that occurs widely in the database, subsequent PSI-BLAST iterations can, in a ratchet-like manner, come to include the complete domain, even though it does not exist in the query sequence. The problem is due not to faulty statistics, but to faulty alignment. One solution to this problem has been proposed in the literature, but we have adopted what we consider a better remedy, based upon trimming alignments at each end by a certain number of bits. Preliminary tests of this approach have been promising, and development of this method continues. No publications have yet resulted.