VDJ Sequence D Gene Assignment Scoring Schema
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Solution Overview
Problem
Current methods for assigning D genes in VDJ sequences are not confident and inconsistent, particularly due to the short length of D genes and heavy editing during somatic hypermutation and V(D)J recombination, leading to inaccurate determination of junction region structure.
Innovation Solution
A method involving the alignment of VDJ sequences to VDJ reference sequences using a scoring schema that applies affine gap penalty functions and scoring adjustments to identify the D gene segment region with the highest score, ensuring accurate D gene segment assignment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current D gene assignment methods are used, then analysis can be performed, but accuracy and consistency of assignment is poor
Solution Approach 1:
The method segments the alignment process into multiple candidate D gene assignments and evaluates each independently using a scoring schema, then selects the optimal assignment. This segmentation allows comprehensive evaluation of multiple possibilities rather than relying on a single ambiguous alignment, thereby improving both accuracy and consistency of D gene assignment.
Solution Approach 2:
The patent introduces a scoring schema with adjustable parameters (affine gap penalties, substitution matrices, etc.) to evaluate and compare different D gene assignments. By optimizing these parameters, the system achieves more reliable and consistent assignments compared to unparameterized or simple alignment methods.
2Measurement precision
If D genes are aligned to transcript bases, then junction region structure can be determined, but the alignment may be incorrect due to editing and recombination
Solution Approach 1:
The method performs preliminary alignment of the VDJ sequence to multiple reference sequences before final D gene assignment. This preliminary action generates multiple candidate alignments that can be evaluated and compared, allowing the system to identify the correct D gene assignment even in the presence of somatic hypermutation and recombination edits.
Solution Approach 2:
The scoring schema provides feedback on the quality of each alignment by calculating scores based on match/mismatch rates and gap penalties. This feedback mechanism allows the system to iteratively improve the alignment and identify the most reliable D gene assignment, correcting for errors introduced by biological editing processes.
3Productivity
If simple alignment methods are used, then processing is fast, but D gene assignment confidence is low
Solution Approach 1:
The method performs more alignment operations than a simple single alignment would suggest, evaluating multiple candidate D gene assignments simultaneously. While this excessive action (multiple alignments) reduces processing speed compared to a single alignment, it dramatically improves assignment confidence and reliability by considering all possibilities.
Data Source
AI summary
A method is provided for identifying one or more D gene segment in a VDJ or VDDJ sequence. The method can include obtaining a B cell receptor and/or T cell receptor data set, wherein the data set includes a VDJ sequence, aligning the VDJ sequence to one or more VDJ reference sequences thereby generating a first potential alignment and a second potential alignment, determining a first score for the first potential alignment and a second score for the second potential alignment in accordance with a D gene segment alignment scoring schema, and identifying a D gene segment region associated with a highest score between the first score and the second score.