Pathway-enhanced Transformer-based model for robust enumeration of cell types from the cell-free transcriptome
Analyzing cell types of origin of cell-free RNA can enhance the resolution of liquid biopsies, thereby deepening the understanding of molecular and cellular changes in development and disease processes. Existing deconvolution methods typically rely on meticulously curated gene expression profiles or employ deep neural network with vast and complex solution spaces that are difficult to interpret. These approaches overlook the synergistic and co-expression effects among genes in biological signaling pathways, compromising their generalizability and robustness. we developed 'Deconformer', a Transformer-based deconvolution model that integrates biological signaling pathways at the embedding stage, to address these issues. Compared to popular methods on multiple datasets, Deconformer demonstrates superior performance and robustness, and is capable of tracking the developmental process of the fetal and placenta. Additionally, pathway-level interpretability of Deconformer offers new insights into crosstalk, dependencies, and other interactions within cell-free RNA pathways, supporting further biological discoveries. We posit that Deconformer represents a significant advancement in the precise analysis of the cell-free transcriptome. It holds the promise of describing disease progression and severity with a new level of accuracy, focusing on the contributions of originating cell types and their pathway dependencies. This model has the potential to catalyze the development of non-invasive diagnostic tools and enhance our understanding of the underlying biology of diseases..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 24. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yan, Shuo [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2024.02.28.582494 |
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| PPN (Katalog-ID): |
XBI042676614 |
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| 520 | |a Analyzing cell types of origin of cell-free RNA can enhance the resolution of liquid biopsies, thereby deepening the understanding of molecular and cellular changes in development and disease processes. Existing deconvolution methods typically rely on meticulously curated gene expression profiles or employ deep neural network with vast and complex solution spaces that are difficult to interpret. These approaches overlook the synergistic and co-expression effects among genes in biological signaling pathways, compromising their generalizability and robustness. we developed 'Deconformer', a Transformer-based deconvolution model that integrates biological signaling pathways at the embedding stage, to address these issues. Compared to popular methods on multiple datasets, Deconformer demonstrates superior performance and robustness, and is capable of tracking the developmental process of the fetal and placenta. Additionally, pathway-level interpretability of Deconformer offers new insights into crosstalk, dependencies, and other interactions within cell-free RNA pathways, supporting further biological discoveries. We posit that Deconformer represents a significant advancement in the precise analysis of the cell-free transcriptome. It holds the promise of describing disease progression and severity with a new level of accuracy, focusing on the contributions of originating cell types and their pathway dependencies. This model has the potential to catalyze the development of non-invasive diagnostic tools and enhance our understanding of the underlying biology of diseases. | ||
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| 700 | 1 | |a Qin, Yulong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jiayi |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Tingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Dongyue |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Wentao |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Jinghua |e verfasserin |0 (orcid)0000-0002-0439-9229 |4 aut | |
| 700 | 1 | |a Hu, Chengbin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Qing |e verfasserin |0 (orcid)0000-0002-9900-3353 |4 aut | |
| 700 | 1 | |a Liu, Zhongzhen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wen-Jing |e verfasserin |0 (orcid)0000-0002-4527-1168 |4 aut | |
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