SAGEPhos: Sage Bio-Coupled and Augmented Fusion for Phosphorylation Site Detection

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Hauptverfasser: Zhang, Jingjie, Cao, Hanqun, Gao, Zijun, Wang, Xiaorui, Gu, Chunbin
Format: Preprint
Veröffentlicht: 2025
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author Zhang, Jingjie
Cao, Hanqun
Gao, Zijun
Wang, Xiaorui
Gu, Chunbin
author_facet Zhang, Jingjie
Cao, Hanqun
Gao, Zijun
Wang, Xiaorui
Gu, Chunbin
contents Phosphorylation site prediction based on kinase-substrate interaction plays a vital role in understanding cellular signaling pathways and disease mechanisms. Computational methods for this task can be categorized into kinase-family-focused and individual kinase-targeted approaches. Individual kinase-targeted methods have gained prominence for their ability to explore a broader protein space and provide more precise target information for kinase inhibitors. However, most existing individual kinase-based approaches focus solely on sequence inputs, neglecting crucial structural information. To address this limitation, we introduce SAGEPhos (Structure-aware kinAse-substrate bio-coupled and bio-auGmented nEtwork for Phosphorylation site prediction), a novel framework that modifies the semantic space of main protein inputs using auxiliary inputs at two distinct modality levels. At the inter-modality level, SAGEPhos introduces a Bio-Coupled Modal Fusion method, distilling essential kinase sequence information to refine task-oriented local substrate feature space, creating a shared semantic space that captures crucial kinase-substrate interaction patterns. Within the substrate's intra-modality domain, it focuses on Bio-Augmented Fusion, emphasizing 2D local sequence information while selectively incorporating 3D spatial information from predicted structures to complement the sequence space. Moreover, to address the lack of structural information in current datasets, we contribute a new, refined phosphorylation site prediction dataset, which incorporates crucial structural elements and will serve as a new benchmark for the field. Experimental results demonstrate that SAGEPhos significantly outperforms baseline methods. We release the SAGEPhos models and code at https://github.com/ZhangJJ26/SAGEPhos.
format Preprint
id arxiv_https___arxiv_org_abs_2502_07384
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle SAGEPhos: Sage Bio-Coupled and Augmented Fusion for Phosphorylation Site Detection
Zhang, Jingjie
Cao, Hanqun
Gao, Zijun
Wang, Xiaorui
Gu, Chunbin
Computational Engineering, Finance, and Science
Phosphorylation site prediction based on kinase-substrate interaction plays a vital role in understanding cellular signaling pathways and disease mechanisms. Computational methods for this task can be categorized into kinase-family-focused and individual kinase-targeted approaches. Individual kinase-targeted methods have gained prominence for their ability to explore a broader protein space and provide more precise target information for kinase inhibitors. However, most existing individual kinase-based approaches focus solely on sequence inputs, neglecting crucial structural information. To address this limitation, we introduce SAGEPhos (Structure-aware kinAse-substrate bio-coupled and bio-auGmented nEtwork for Phosphorylation site prediction), a novel framework that modifies the semantic space of main protein inputs using auxiliary inputs at two distinct modality levels. At the inter-modality level, SAGEPhos introduces a Bio-Coupled Modal Fusion method, distilling essential kinase sequence information to refine task-oriented local substrate feature space, creating a shared semantic space that captures crucial kinase-substrate interaction patterns. Within the substrate's intra-modality domain, it focuses on Bio-Augmented Fusion, emphasizing 2D local sequence information while selectively incorporating 3D spatial information from predicted structures to complement the sequence space. Moreover, to address the lack of structural information in current datasets, we contribute a new, refined phosphorylation site prediction dataset, which incorporates crucial structural elements and will serve as a new benchmark for the field. Experimental results demonstrate that SAGEPhos significantly outperforms baseline methods. We release the SAGEPhos models and code at https://github.com/ZhangJJ26/SAGEPhos.
title SAGEPhos: Sage Bio-Coupled and Augmented Fusion for Phosphorylation Site Detection
topic Computational Engineering, Finance, and Science
url https://arxiv.org/abs/2502.07384