Electronic methods and systems for microorganism characterization
Inventors
Fry, Stephen E. • Ellis, Jeremy • Shabilla, Matthew
Assignees
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Publication Number
US-10204209-B2
Publication Date
2019-02-12
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 provides electronic methods and systems for identifying one or more microorganisms or DNA fragments thereof from a DNA sequence data set at a computer system. It performs a multi-pronged assessment of potential alignments by generating one or more first alignment results by comparing the DNA sequence data set to each of one or more first reference data sets stored in a first database, and by generating a plurality of second alignment results by comparing at least part of the DNA sequence data set to each of a plurality of second reference data sets stored in a second database, where the plurality of second reference data sets includes more reference data sets than included in the one or more first reference data sets.
The method determines that the one or more first alignment results failed to indicate at least one alignment match and that the plurality of second alignment results also failed to indicate at least one alignment match, between the DNA sequence data set and any reference data set. In response to this determination, it compares at least one of the one or more first alignment results with at least one of the plurality of second alignment results, and selects, based on the comparison, a particular reference data set to associate with the DNA sequence data set.
Based on the selected particular reference data set, the method outputs an identification of one or more microorganisms or DNA fragments thereof. The disclosed approach includes segmenting DNA sequence data into window-based subsets and performing alignment using subsets, with re-segmentation using a different window size when no alignment match is found. The workflow is implemented in electronic systems that include automatic sequence-run detection, local processing, parallel processing, and automatic report generation that includes treatment sensitivity and therapy-resistance information.
Claims Coverage
Independent claims cover a multi-pronged alignment assessment workflow that generates first and second alignment results against reference data sets stored in separate databases, determines failure to indicate alignment matches, compares alignment results to select a particular reference data set, and outputs an identification of microorganisms or DNA fragments. The inventive features include a two-database alignment assessment and selection of a particular reference data set based on comparing alignment results after both prongs fail to indicate an alignment match.
Multi-pronged assessment with first and second databases
Generating one or more first alignment results by comparing the DNA sequence data set to each of one or more first reference data sets stored in a first database; and generating a plurality of second alignment results by comparing at least part of the DNA sequence data set to each of a plurality of second reference data sets stored in a second database, the plurality of second reference data sets including more reference data sets than included in the one or more first reference data sets.
Failure to indicate alignment match for both databases
Determining that the one or more first alignment results failed to indicate at least one alignment match between the DNA sequence data set and any reference data set of the one or more first reference data sets and that the plurality of second alignment results failed to indicate at least one alignment match between the DNA sequence data set and any of the plurality of second reference data sets.
Compare alignment results and select a particular reference data set
In response to the determination that the one or more first alignment results failed to indicate at least one alignment match and that the plurality of second alignment results failed to indicate at least one alignment match, comparing at least one of the one or more first alignment results with at least one of the plurality of second alignment results; selecting, based on the comparison, a particular reference data set to associate with the DNA sequence data set, the particular reference data set being one of the one or more first reference data sets associated with the first database or one of the plurality of second reference data sets associated with the second database.
Output identification based on selected reference data set
Outputting an identification of one or more microorganisms or DNA fragments thereof based on the selected particular reference data set.
The independent claims collectively require a two-database multi-pronged alignment assessment, a determination that both alignment prongs fail to indicate an alignment match, a comparison of alignment results to select a particular reference data set, and outputting an identification based on the selected reference data set.
Stated Advantages
Enables outputting an identification of one or more microorganisms or DNA fragments thereof based on a selected particular reference data set after comparing alignment results from first and second databases.
Supports a multi-pronged assessment that uses a second database including more reference data sets than the first database.
Documented Applications
Rapid characterization of one or more microorganisms and DNA fragments from sequencing-derived DNA sequences by generating alignment results against reference databases and selecting a closer match for characterization.
Clinical workflow including automatic sequence-run detection, local processing without sustained Internet, parallel processing for multiple microorganisms, and generating reports including treatment sensitivity and therapy-resistance information.
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