Method and apparatus for biological sequence comparison

G - Physics – 06 – F

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G06F 19/00 (2006.01) G06F 17/30 (2006.01)

Patent

CA 2177764

A method and apparatus for comparing biological sequences from a known source of sequences, with a subject (query) sequence. The apparatus takes as input a set of target similarity levels (such as evolutionary distances given in special units called PAM), and finds all fragments of known sequences that are similar to the subject sequence (or fragment thereof) at each target similarity level, and are long enough to be statistically significant. It examines all possible fragments of all sizes, yet can be implemented very economically. The invention device effectively and efficiently filters out most of the noise and artifacts (false positives and negatives) namely fragments from the known sequences that are too short, or have a lower average similarity to the subject sequence (or fragment thereof) than is required by each target similarity level. The subject sequence is then compared only to the remaining known sequences to find the best matches. The filtering member divides the subject sequence into overlapping blocks, each block being sufficiently large to contain an alignment of a certain minimum length from a known sequence. For each block, the filter member compares the block with every possible short fragment in the source of known sequences and determines a best match for each comparison. The determined set of short fragment best matches for the block provide and upper threshold on alignment values. Regions of a certain length from the known sequences that have a mean alignment value upper bound (threshold) greater than a target unit score (relative entropy) are concatenated to form a union. The current block is compared to the union and provides an indication of best local alignment with the subject sequence. If the best local alignment has a match score of greater than or equal to 20 bits then the subject sequence is compared against the source sequence containing the regions of the union.

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