Index Hopping Filtering Using Hash Data Structures
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Solution Overview
Problem
Current methods for detecting index hopping in multiplexed sequencing data are inadequate, particularly in the presence of sequencing errors, and often rely on exact matching, which is computationally expensive and ineffective.
Innovation Solution
A system and method that uses hash data structures to identify and filter out erroneous sequence reads by forming hash values from unique molecular identifiers and sample indices, allowing for the detection of index hopping without exact matching, thereby reducing computational expense.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If exact matching methods are used to detect index hopping, then measurement precision is improved, but computational expense increases significantly
Solution Approach 1:
The patent replaces the mechanical/computational system of exact string matching with a hash-based computational system. By converting unique molecular identifiers and sample indices into hash values, the system achieves efficient comparison without requiring exhaustive exact matching, thus improving computational efficiency while maintaining detection capability
Solution Approach 2:
The patent transforms the detection parameters by converting exact sequence matching into hash value comparison. This parameter transformation allows the system to detect index hopping through hash collisions rather than requiring complete sequence identity, reducing the computational complexity from O(n²) exact matching to more efficient hash-based comparison
2Measurement precision
If exact matching is used to identify index-hopped reads, then detection accuracy is improved, but the complexity of the system increases
Solution Approach 1:
The patent substitutes the complex mechanical process of exact string comparison with a simpler hash-based system. By computing hash values of unique molecular identifiers and sample indices, the system reduces computational complexity while maintaining the ability to detect index hopping events through hash value analysis
3Productivity
If the number of search comparisons is reduced using hash values, then productivity is improved, but measurement precision may deteriorate
Solution Approach 1:
The patent replaces exact matching mechanics with hash-based comparison mechanics. By using hash values derived from unique molecular identifiers and sample indices, the system achieves fast comparison speed while maintaining detection accuracy through the mathematical properties of hash functions that preserve uniqueness for the intended application
Data Source
AI summary
Methods for index hopping sequence read filtering are provided. Each read in a plurality of reads from a multiplexed reaction comprises an insert portion, and first (molecular identifier) and second (sample index) non-insert portions. For each of a plurality of hashes, a hash data structure is formed with a representation of each read. Each representation comprises a hash of the first non-insert portion of the corresponding read. Read pairs are identified in the hash data structures. Each pair includes a first and second read sharing a common hash value but differing index values. An entry is added into a heterogeneous data structure, for each such pair, that includes the first and second non-insert portions of the first and second reads of the pair. Reads with first non-insert portion values appearing more than a threshold number of times in the heterogeneous data structure are removed from the plurality of reads.