Quantitative Biology

   

Reshaping ESM-2 Representation Geometry for Viral Protein Classification

Authors: Ishir Rao

Distinguishing viral proteins from their human host counterparts is a fundamental challenge in computational virology, with direct implications for gene therapy vector design and antiviral therapeutics. We present a systematic comparison of three classification frameworks on 26,771 SwissProt-reviewed sequences (6,350 viral, 20,421 human): a TF-IDF k-mer Random Forest baseline, a logistic regression probe on frozen ESM-2 embeddings [1], and a supervised contrastive learning (SupCon [2]) projection head trained on those same embeddings. The k-mer baseline achieves84% overall accuracy but fails on viral sequences (recall = 40%), while ESM-2 embeddings alone raise accuracy to 98% and viral recall to 96%, confirming that evolutionary pretraining encodes substantial host—viral discriminative signal without any task-specific supervision. Supervised contrastive fine-tuning further improves overall accuracy to 98.69%and viral F1 to 0.97, but the most consequential gains appear among proteins where biology itself is ambiguous: viral sequences that have evolved human-like surface features to evade immune detection show a disproportionate improvement under contrastive training, with mean classification accuracy on host-mimicry proteins rising from 55.5%(k-mers) to 69.4% (ESM-2) to 96.1% (ESM-2 + SupCon) — a 26.7 percentage-point leap attributable directly to the contrastive objective. Manifold analysis via UMAP confirms that SupCon progressively restructures the embedding geometry over training, tightening intra-class cohesion and widening the inter-class margin in precisely the regions where host and viral proteomes overlap most.

Comments: 8 Pages.

Download: PDF

Submission history

[v1] 2026-04-10 20:07:00

Unique-IP document downloads: 80 times

Vixra.org is a pre-print repository rather than a journal. Articles hosted may not yet have been verified by peer-review and should be treated as preliminary. In particular, anything that appears to include financial or legal advice or proposed medical treatments should be treated with due caution. Vixra.org will not be responsible for any consequences of actions that result from any form of use of any documents on this website.

Add your own feedback and questions here:
You are equally welcome to be positive or negative about any paper but please be polite. If you are being critical you must mention at least one specific error, otherwise your comment will be deleted as unhelpful.

comments powered by Disqus