MAGNET: Understanding and Improving the Accuracy of Genome Pre-Alignment Filtering

In the era of high throughput DNA sequencing (HTS) technologies, calculating the edit distance (i.e., the minimum number of substitutions, insertions, and deletions between a pair of sequences) for billions of genomic sequences is the computational bottleneck in today's read mappers. The shifted Hamming distance (SHD) algorithm proposes a fast filtering strategy that can rapidly filter out invalid mappings that have more edits than allowed. However, SHD shows high inaccuracy in its filtering by admitting invalid mappings to be marked as correct ones. This wastes the execution time and imposes a large computational burden. In this work, we comprehensively investigate four sources that lead to the filtering inaccuracy. We propose MAGNET, a new filtering strategy that maintains high accuracy across different edit distance thresholds and data sets. It significantly improves the accuracy of pre-alignment filtering by one to two orders of magnitude. The MATLAB implementations of MAGNET and SHD are open source and available at: https://github.com/BilkentCompGen/MAGNET.