mlsanityData to 14 Oct 2026

When do cheap embeddings beat protein language models? A theoretically-grounded hashing sketch for biological sequence classification

arXiv 2512.10147 ↗First posted 10 Dec 2025cs.LG q-bio.GNcited by 0

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Abstract (arXiv)

Motivation: Pre-trained protein language models (PLMs) such as ESM-2 have become the default representation for biological sequence tasks, but they are computationally heavy and require GPUs both for embedding and for fine-tuning. Whether they are actually necessary for sequence classification, as opposed to structure prediction, is rarely tested against strong, principled, lightweight alternatives. This question has direct practical stakes for large-scale genomic surveillance, where embedding millions of sequences on commodity hardware is a recurring bottleneck. Results: We introduce Murmur2Vec, an alignment-free, training-free embedding that aggregates k-mer counts into a small hash table via the deterministic MurmurHash function, and we cast it as a randomized sketch of the classical k-mer spectrum kernel. We provide a complete theoretical treatment: closed-form bias/variance of the inner product, an unbiased signed variant with a Johnson--Lindenstrauss-type concentration bound, an excess-risk bound for downstream linear classifiers that makes the bias--variance trade-off in the hash-table size explicit, and an implicit-regularization mechanism by which collisions damage frequent non-discriminative k-mers more than rare lineage-defining ones. Across four classification tasks, SARS-CoV-2 spike lineage (22 classes), HIV-1 Env subtype (8 classes), and two protein-family benchmarks (8 and 6 classes), Murmur2Vec matches a LoRA-fine-tuned 650M-parameter ESM-2 model on the two tasks for which LoRA fine-tuning was run to convergence (SARS-CoV-2 and HIV-1) and ties frozen ESM-2 on the two protein-family tasks, and it outperforms the fine-tuned model on the hardest task (SARS-CoV-2 lineage: 0.854 vs. 0.807 accuracy; macro-F1 0.684 vs. 0.401).

Key facts. No citing papers in the map yet (data through 14 Oct 2026). Builds on 11 of its 32 references that are in the map. First posted on arXiv 10 Dec 2025.

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References · 11

  1. 2015Unsupervised Deep Embedding for Clustering Analysiscited by 767
  2. 2022Why do tree-based models still outperform deep learning on tabular data?cited by 199
  3. 2013Dropout Training as Adaptive Regularizationcited by 93
  4. 2020Uncertainty in Gradient Boosting via Ensemblescited by 56
  5. 2021Spike2Vec: An Efficient and Scalable Embedding Approach for COVID-19 Spike Sequencescited by 30
  6. 2021A k-mer Based Approach for SARS-CoV-2 Variant Identificationcited by 23
  7. 2022PWM2Vec: An Efficient Embedding Approach for Viral Host Specification from Coronavirus Spike Sequencescited by 22
  8. 2022Efficient Approximate Kernel Based Spike Sequence Classificationcited by 18
  9. 2021Neural Distance Embeddings for Biological Sequencescited by 17
  10. 2021Robust Representation and Efficient Feature Selection Allows for Effective Clustering of SARS-CoV-2 Variantscited by 14
  11. 2017GaKCo: a Fast GApped k-mer string Kernel using COuntingcited by 11

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