Enhanced Detection of Novel Low-Frequency Gene Fusions via High-Yield Ligation and Multiplexed Enrichment Sequencing
© 2024 Wiley‐VCH GmbH..
Panel-based methods are commonly employed for the analysis of novel gene fusions in precision diagnostics and new drug development in cancer. However, these methods are constrained by limitations in ligation yield and the enrichment of novel gene fusions with low variant allele frequencies. In this study, we conducted a pioneering investigation into the stability of double-stranded adapter DNA, resulting in improved ligation yield and enhanced conversion efficiency. Additionally, we implemented blocker displacement amplification, achieving a remarkable 7-fold enrichment of novel gene fusions. Leveraging the pre-enrichment achieved with this approach, we successfully applied it to Nanopore sequencing, enabling ultra-fast analysis of novel gene fusions within one hour with high sensitivity. This method offers a robust and remarkably sensitive mean of analyzing novel gene fusions, promising the discovery of pivotal biomarkers that can significantly improve cancer diagnostics and the development of new therapeutic strategies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:63 |
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| Enthalten in: |
Angewandte Chemie (International ed. in English) - 63(2024), 18 vom: 24. Apr., Seite e202316484 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Yi [VerfasserIn] |
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| Links: |
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| Themen: |
9007-49-2 |
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| Anmerkungen: |
Date Completed 19.04.2024 Date Revised 19.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/anie.202316484 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369841182 |
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| 520 | |a Panel-based methods are commonly employed for the analysis of novel gene fusions in precision diagnostics and new drug development in cancer. However, these methods are constrained by limitations in ligation yield and the enrichment of novel gene fusions with low variant allele frequencies. In this study, we conducted a pioneering investigation into the stability of double-stranded adapter DNA, resulting in improved ligation yield and enhanced conversion efficiency. Additionally, we implemented blocker displacement amplification, achieving a remarkable 7-fold enrichment of novel gene fusions. Leveraging the pre-enrichment achieved with this approach, we successfully applied it to Nanopore sequencing, enabling ultra-fast analysis of novel gene fusions within one hour with high sensitivity. This method offers a robust and remarkably sensitive mean of analyzing novel gene fusions, promising the discovery of pivotal biomarkers that can significantly improve cancer diagnostics and the development of new therapeutic strategies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Gene fusions detection | |
| 650 | 4 | |a Gene sequencing | |
| 650 | 4 | |a Ligation yield | |
| 650 | 4 | |a Selective enrichment | |
| 650 | 4 | |a Thermodynamics | |
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| 700 | 1 | |a Guo, Jinxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Wenjun |e verfasserin |4 aut | |
| 700 | 1 | |a Xiu, Xuehao |e verfasserin |4 aut | |
| 700 | 1 | |a Thirunavukarasu, Deepak |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yudong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Weiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Yu Zhang, David |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xiurong |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Chunhai |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Ping |e verfasserin |4 aut | |
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