Biological meaning in protein embedding space is resolution-dependent
Licheng ZongiD, Jinzheng ReniD, Yu LiiD, Robert D. FinniD, Jiawei WangiD
Abstract
Protein language model embeddings are increasingly used to organise biological sequences, yet how biological meaning is encoded within embedding neighbourhoods remains poorly understood. Using two independent hierarchical enzyme systems, carbohydrate-active enzymes and peptidases, we investigated how biological interpretation changes across embedding organisations aligned to different levels of biological hierarchy. Different embedding organisations give rise to distinct neighbourhood semantics. When aligned to membership-boundary resolution, embeddings robustly separated artefacts and unrelated proteins from members of the target category. However, embeddings aligned to functional-grouping resolution maintained compositional neighbourhood structure for multi-domain proteins spanning more than one functional or catalytic group. Finally, embeddings aligned to local-family resolution recovered compact family-like neighbourhoods, including families withheld from training, while weakening broader membership-boundary and functional-grouping relationships. Moreover, embeddings optimised toward the same level of biological organisation retain different biological relationships depending on optimisation trajectory employed. Together, our results show that proximity in protein embedding space has no fixed biological interpretation. Instead, biological meaning emerges across embedding resolutions through selective preservation of different forms of biological organisation.
02 /Specification & Classification
Click any tag to browse matching papers- Citations
- 0
- Assay
- Approach
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- dom2vec: Unsupervised protein domain embeddings capture domains structure and function providing data-driven insights into collocations in domain architectures
Damianos P. Melidis, Brandon Malone, Wolfgang Nejdl·AlgorithmsPeer-reviewed·Jan 19, 2021
- High-resolution dissection of concept acquisition in different families of protein language models
Shawn Whitfield, Tom Marty, … Quentin Fournier·bioRxiv·Jul 23, 2026
- Decoding protein language models: insights from embedding space analysis
Pia Francesca Rissom, Vít Škrhák, … Sumaiya Iqbal·PatternsPeer-reviewed·Aug 12, 2026
- Quantifying uncertainty in Protein Representations Across Models and Task
R. Prabakaran, Yana Bromberg·Nature MethodsPeer-reviewed·Apr 1, 2026
- Nearest neighbor search on embeddings rapidly identifies distant protein relations
Konstantin Schütze, Michael Heinzinger, … Burkhard Rost·Frontiers in BioinformaticsPeer-reviewed·Nov 17, 2022
- Inferring Protein Domain Semantic Roles Using word2vec
Daniel W. A. Buchan, David T. Jones·bioRxiv·Apr 24, 2019