Integrating Protein Sequence and Expression Level to Analysis Molecular Characterization of Breast Cancer Subtypes
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| Format: | Preprint |
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2024
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| author | Sholehrasa, Hossein Jaberi-Douraki, Majid |
| author_facet | Sholehrasa, Hossein Jaberi-Douraki, Majid |
| contents | Breast cancer's complexity and variability pose significant challenges in understanding its progression and guiding effective treatment. This study aims to integrate protein sequence data with expression levels to improve the molecular characterization of breast cancer subtypes and predict clinical outcomes. Using ProtGPT2, a language model specifically designed for protein sequences, we generated embeddings that capture the functional and structural properties of proteins. These embeddings were integrated with protein expression levels to form enriched biological representations, which were analyzed using machine learning methods, such as ensemble K-means for clustering and XGBoost for classification. Our approach enabled the successful clustering of patients into biologically distinct groups and accurately predicted clinical outcomes such as survival and biomarker status, achieving high performance metrics, notably an F1 score of 0.88 for survival and 0.87 for biomarker status prediction. Feature importance analysis identified KMT2C, CLASP2, and MYO1B as key proteins involved in hormone signaling, cytoskeletal remodeling, and therapy resistance in hormone receptor-positive and triple-negative breast cancer, with potential influence on breast cancer subtype behavior and progression. Furthermore, protein-protein interaction networks and correlation analyses revealed functional interdependencies among proteins that may influence the behavior and progression of breast cancer subtypes. These findings suggest that integrating protein sequence and expression data provides valuable insights into tumor biology and has significant potential to enhance personalized treatment strategies in breast cancer care. |
| format | Preprint |
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arxiv_https___arxiv_org_abs_2410_01755 |
| institution | arXiv |
| publishDate | 2024 |
| record_format | arxiv |
| spellingShingle | Integrating Protein Sequence and Expression Level to Analysis Molecular Characterization of Breast Cancer Subtypes Sholehrasa, Hossein Jaberi-Douraki, Majid Biomolecules Machine Learning Breast cancer's complexity and variability pose significant challenges in understanding its progression and guiding effective treatment. This study aims to integrate protein sequence data with expression levels to improve the molecular characterization of breast cancer subtypes and predict clinical outcomes. Using ProtGPT2, a language model specifically designed for protein sequences, we generated embeddings that capture the functional and structural properties of proteins. These embeddings were integrated with protein expression levels to form enriched biological representations, which were analyzed using machine learning methods, such as ensemble K-means for clustering and XGBoost for classification. Our approach enabled the successful clustering of patients into biologically distinct groups and accurately predicted clinical outcomes such as survival and biomarker status, achieving high performance metrics, notably an F1 score of 0.88 for survival and 0.87 for biomarker status prediction. Feature importance analysis identified KMT2C, CLASP2, and MYO1B as key proteins involved in hormone signaling, cytoskeletal remodeling, and therapy resistance in hormone receptor-positive and triple-negative breast cancer, with potential influence on breast cancer subtype behavior and progression. Furthermore, protein-protein interaction networks and correlation analyses revealed functional interdependencies among proteins that may influence the behavior and progression of breast cancer subtypes. These findings suggest that integrating protein sequence and expression data provides valuable insights into tumor biology and has significant potential to enhance personalized treatment strategies in breast cancer care. |
| title | Integrating Protein Sequence and Expression Level to Analysis Molecular Characterization of Breast Cancer Subtypes |
| topic | Biomolecules Machine Learning |
| url | https://arxiv.org/abs/2410.01755 |