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https://doi.org/10.21203/rs.3....
Article . 2026 . Peer-reviewed
License: CC BY
Data sources: Crossref
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ZENODO
Other literature type . 2026
License: CC BY
Data sources: ZENODO
ZENODO
Other literature type . 2026
License: CC BY
Data sources: Datacite
ZENODO
Other literature type . 2026
License: CC BY
Data sources: Datacite
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Affinity Map: Few-Shot Protein Family Classification via Prototypical Networks: Benchmarking Sequence Encoders and Episodic ESM-2 Fine-Tuning

Authors: Deraz Nasr, Mohamed;

Affinity Map: Few-Shot Protein Family Classification via Prototypical Networks: Benchmarking Sequence Encoders and Episodic ESM-2 Fine-Tuning

Abstract

Abstract Protein family annotation is a cornerstone of computational biology, yet the acquisition of large, curated per-family corpora is laborious and often infeasible for rare families. We present Affinity Map, a meta-learning pipeline that frames protein family classification as a few-shot learning problem: given only K labelled examples from a previously unseen family, the model must correctly assign new sequences to that family. We systematically benchmark encoder quality under this episodic framework, ranging from a lightweight 1D-CNN trained from scratch through compositional k-mer baselines to a frozen ESM-2 protein language model and episodic LoRA fine-tuning, all evaluated under Prototypical Networks with N-way K-shot tasks sampled from the Pfam database. Evaluating on 24 held-out test families reveals: (1) CNN ProtoNet trained from scratch reaches 71.0% at K=5; (2) 3-mer frequency k-mer ProtoNet reaches 86.2%; (3) a frozen ESM-2 encoder reaches 88.7% at K=5; and (4) episodic LoRA fine-tuning of ESM-2 reveals a K-dependent interaction: LoRA gains +2.5 pp over frozen ESM-2 at K=1 (p < 0.001), but underperforms frozen ESM-2 at K >= 2, indicating that episodic adaptation improves single-shot retrieval at the cost of multi-shot prototype quality. All pairwise CNN vs. baseline differences are statistically significant (paired Wilcoxon, p < 0.001). Real per-epoch learning curves, a named confusion matrix, PCA/UMAP embedding visualisations, and comprehensive baseline comparisons provide biologically interpretable diagnostics throughout. All code and results are publicly available.

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Keywords

prototypical networks, meta-learning, protein sequence analysis, few-shot learning, bioinformatics, ESM-2, protein language models, LoRA

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
hybrid