| Title: |
PLM-eXplain: Divide and Conquer the Protein Embedding Space |
| Authors: |
van Eck, Jan; Gogishvili, Dea; Silva, Wilson; Abeln, Sanne; Sub AI Technology for Life; Sub Biology AI Technology For Life |
| Publication Year: |
2026 |
| Subject Terms: |
Statistics and Probability; Biochemistry; Molecular Biology; Computer Science Applications; Computational Theory and Mathematics; Computational Mathematics |
| Description: |
MOTIVATION: Protein language models (PLMs) have revolutionized computational biology through their ability to generate powerful sequence representations for diverse prediction tasks. However, their black-box nature limits biological interpretation and translation to actionable insights. Bridging this gap requires approaches that maintain predictive performance while providing interpretable explanations of model behaviour. RESULTS: We present PLM-eXplain (PLM-X), an explainable adapter layer that bridges this gap by factoring PLM embeddings into two complementary components: an interpretable subspace based on established biochemical features, and a residual subspace that retains predictive, non-interpretable information. Using embeddings from ESM2 and ProtBert, PLM-X incorporates well-established properties, including secondary structure and hydropathy, while maintaining high predictive performance. We demonstrate the effectiveness of our approach across three biologically relevant classification tasks: extracellular vesicle association, transmembrane helix prediction, and aggregation propensity prediction. PLM-X enables biological interpretation of model decisions without sacrificing accuracy, offering a generalizable solution for enhancing PLM interpretability across various downstream applications. AVAILABILITY AND IMPLEMENTATION: Source code and models are available at https://github.com/AIT4LIFE-UU/PLM-eXplain/. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
1367-4803 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/480132 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/480132 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.CDD87F7B |
| Database: |
BASE |