Electronic methods and systems for microorganism characterization

Inventors

Fry, Stephen E.Ellis, JeremyShabilla, Matthew

Assignees

Fry Laboratories LLC

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Publication Number

US-9971867-B2

Patent

Publication Date

2018-05-15

Expiration Date


Abstract

Systems and methods to characterize one or more microorganisms or DNA fragments thereof are disclosed. Exemplary methods and systems use comparison of DNA sequencing information to information in one or more databases to characterize the one or more microorganism or DNA fragments thereof. Exemplary systems and methods can be used in a clinical setting to provide rapid analysis of microorganisms that may be a cause of infection.

Core Innovation

The invention relates to electronic systems and methods for characterizing one or more microorganisms using DNA sequence data sets. A computer system accesses a data set that includes a plurality of DNA sequence data sets and generates, for each DNA sequence data set, a first alignment result by comparing the DNA sequence data set to one or more first data sets stored in a first database.

For second alignment results, the method segments each DNA sequence data set into one or more second data sets using a window of a window size, and performs iterative alignment actions by comparing the one or more second data sets to information stored in a second database. The method determines whether the comparison fails to produce at least one alignment match between any second data set and information stored in the second database.

When the comparison fails to produce at least one alignment match and the window size has not decreased beyond a designated stringency level, the method decreases the window size and repeats the segmenting and iterative alignment actions. The invention characterizes one or more microorganisms based on the first alignment results and the second alignment results, including a strategy that increases stringency through decreased window size up to a maximum stringency cutoff.

Claims Coverage

The independent claims comprise 3 claim types: method, system, and computer-program product. They share a common core of first alignment against a first database followed by iterative, windowed second alignment against a second database with decreased window size under a stringency level.

First alignment against a first database

Generating, by the computer system, for each DNA sequence data set, a first alignment result by comparing the DNA sequence data set to each of one or more first data sets stored in a first database.

Windowed segmentation and iterative second alignment against a second database

Generating a second alignment result for at least some of the plurality of DNA sequence data sets by segmenting the DNA sequence data set into one or more second data sets using a window of a window size, performing iterative alignment actions including comparing the one or more second data sets to information stored in a second database, and determining whether the comparison failed to produce at least one alignment match between any second data set and information stored in the second database.

Decreasing window size until a designated stringency level

When it is determined that the comparison failed to produce at least one alignment match and when the window size has not decreased beyond a designated stringency level, decreasing the window size, repeating the segmenting using the decreased window size, and repeating the set of iterative alignment actions.

Characterizing microorganisms based on first and second alignment results

Characterizing one or more microorganisms based on the first alignment results and the second alignment results.

First database has fewer sequences than the second database

Generating, for each DNA sequence data set, first and second alignment results where the first database holds fewer sequences than the second database.

First and second matching values indicating extent of match

Aligning to produce first and second matching values that indicate the extent of match for each DNA sequence data set against sequences from the respective databases.

Match determination within predetermined criteria or tolerance

Using a first alignment result to determine whether the DNA sequence data set matches within a predetermined criteria or tolerance a sequence in stored first data sets in a first database, and determining failure of the second comparison using whether at least one alignment match is produced between second data sets and information stored in the second database.

Excluding first-matching sequence data sets from further iterative alignment

Identifying one or more first DNA sequence data sets from a plurality based on alignment results that match within a predetermined tolerance and excluding those identified first DNA data sets from further iterative alignment actions.

Each DNA sequence data set contains a DNA sequence or a portion of a DNA sequence

Each of the DNA sequence data sets contains a DNA sequence or portion of a DNA sequence.

Across the independent method, system, and computer-program product claims, the document emphasizes a two-stage alignment approach: first alignment against a first database, then iterative windowed segmentation and alignment against a second database with window size decreased under a designated stringency level when matches are not produced. Dependent claims further specify quantitative matching outputs, tolerance- or criteria-based match determinations, a comparative database-size relationship, optional exclusion of certain first-matching data sets from further iterative alignment, and the granularity of DNA sequence data sets.

Stated Advantages

Not explicitly described in patent.

Documented Applications

Not explicitly described in patent.

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