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Faster, more accurate, more sensitive
Date:12/25/2011

ins are stored, together with information on their biological functions, which facilitates such comparisons. "This kind of sequence analysis is a fundamental tool in the field of bioinformatics," explains Sding.

The sequence search programs assess sequence similarity by computing pairwise alignments: the two sequences of amino acids are arranged one above the other in such a way that mostly identical or similar amino acids are paired up in the same columns. "Perhaps even more important than the search for pairwise sequence similarities is the assembly of so-called multiple sequence alignments; in this case one searches for similar sequences in many related proteins and arranges them into a matrix, in which each sequence fills a row and similar amino acids end up in the same columns" says Sding. Because the functions and structure of evolutionarily related proteins are generally conserved - i.e. preserved even when the sequence is altered by mutations during the course of evolution - multiple sequence alignments form the basis for the prediction of the structure and molecular functions of uncharacterized proteins.

For the past 15 years, the program PSI-BLAST has been the most popular tool for the comparison of protein sequences, as it combines speed with high sensitivity and precision. Now Sding's team has designed a method, called HHblits, which clearly surpasses PSI-BLAST in all aspects of performance. This improvement is largely due to two factors. First the researchers convert both the sequence of interest and the sequences in the database to be searched into so-called Hidden Markov Models (HMMs). HMMs are statistical models that incorporate the mutation probabilities determined from sequence alignments so this step increases the sensitivity and precision of the subsequent similarity search. In addition, the team has developed a filtering procedure that allows them to reduce the amount of data that needs to be searched without appreciable los
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Contact: Simon Kirner
simon.kirner@lmu.de
49-892-180-3174
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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