Prot2Text-V2: Protein Function Prediction with Multimodal Contrastive Alignment

Fuente: arXiv
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Main Authors: Fei, Xiao, Chatzianastasis, Michail, Carneiro, Sarah Almeida, Abdine, Hadi, Petalidis, Lawrence P., Vazirgiannis, Michalis
Format: Preprint
Published: 2025
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author Fei, Xiao
Chatzianastasis, Michail
Carneiro, Sarah Almeida
Abdine, Hadi
Petalidis, Lawrence P.
Vazirgiannis, Michalis
author_facet Fei, Xiao
Chatzianastasis, Michail
Carneiro, Sarah Almeida
Abdine, Hadi
Petalidis, Lawrence P.
Vazirgiannis, Michalis
contents Predicting protein function from sequence is a central challenge in computational biology. While existing methods rely heavily on structured ontologies or similarity-based techniques, they often lack the flexibility to express structure-free functional descriptions and novel biological functions. In this work, we introduce Prot2Text-V2, a novel multimodal sequence-to-text model that generates free-form natural language descriptions of protein function directly from amino acid sequences. Our method combines a protein language model as a sequence encoder (ESM-3B) and a decoder-only language model (LLaMA-3.1-8B-Instruct) through a lightweight nonlinear modality projector. A key innovation is our Hybrid Sequence-level Contrastive Alignment Learning (H-SCALE), which improves cross-modal learning by matching mean- and std-pooled protein embeddings with text representations via contrastive loss. After the alignment phase, we apply instruction-based fine-tuning using LoRA on the decoder to teach the model how to generate accurate protein function descriptions conditioned on the protein sequence. We train Prot2Text-V2 on about 250K curated entries from SwissProt and evaluate it under low-homology conditions, where test sequences have low similarity with training samples. Prot2Text-V2 consistently outperforms traditional and LLM-based baselines across various metrics.
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id arxiv_https___arxiv_org_abs_2505_11194
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Prot2Text-V2: Protein Function Prediction with Multimodal Contrastive Alignment
Fei, Xiao
Chatzianastasis, Michail
Carneiro, Sarah Almeida
Abdine, Hadi
Petalidis, Lawrence P.
Vazirgiannis, Michalis
Computational Engineering, Finance, and Science
Predicting protein function from sequence is a central challenge in computational biology. While existing methods rely heavily on structured ontologies or similarity-based techniques, they often lack the flexibility to express structure-free functional descriptions and novel biological functions. In this work, we introduce Prot2Text-V2, a novel multimodal sequence-to-text model that generates free-form natural language descriptions of protein function directly from amino acid sequences. Our method combines a protein language model as a sequence encoder (ESM-3B) and a decoder-only language model (LLaMA-3.1-8B-Instruct) through a lightweight nonlinear modality projector. A key innovation is our Hybrid Sequence-level Contrastive Alignment Learning (H-SCALE), which improves cross-modal learning by matching mean- and std-pooled protein embeddings with text representations via contrastive loss. After the alignment phase, we apply instruction-based fine-tuning using LoRA on the decoder to teach the model how to generate accurate protein function descriptions conditioned on the protein sequence. We train Prot2Text-V2 on about 250K curated entries from SwissProt and evaluate it under low-homology conditions, where test sequences have low similarity with training samples. Prot2Text-V2 consistently outperforms traditional and LLM-based baselines across various metrics.
title Prot2Text-V2: Protein Function Prediction with Multimodal Contrastive Alignment
topic Computational Engineering, Finance, and Science
url https://arxiv.org/abs/2505.11194