MELO-ED: learning locality-sensitive multi-embeddings for edit distance

Abstract Edit distance is a fundamental metric for quantifying similarity between biological sequences, but its high computational cost limits large-scale applications. Previously, we proposed learned locality-sensitive bucketing (LSB) functions that achieved superior performance and efficiency compared to classical seeding methods for identifying similar and dissimilar sequences. How-ever, each component of an LSB function is represented as a one-dimensional hash value that can only be compared for identity, which constrains the method’s accuracy. Here, we intro-duce MELO-ED, a multi-embedding locality-sensitive framework that upgrades each hash value to a higher-dimensional embedding capable of efficiently approximating edit distance. MELO-ED employs a Siamese convolutional neural architecture that learns complementary embeddings capturing both global sequence context and fine-grained edit operations. By integrating locality-sensitive bucketing with multi-embedding representations, MELO-ED achieves near-perfect ac-curacy without increasing the number of buckets required. Leveraging mature indexing methods in the embedding space, MELO-ED transforms time-consuming edit distance computations into scalable similarity searches across massive genomic databases. Comprehensive evaluations on simulated DNA sequences and real barcode datasets demonstrate that MELO-ED outperforms both traditional alignment-free methods and contemporary machine learning approaches, in-cluding our previously developed learned LSB functions. These results establish MELO-ED as a state-of-the-art framework for fast and accurate classification of similar and dissimilar sequences. MELO-ED is available at https://github.com/Shao-Group/MELO-ED .