Targeted Sequencing of Genomic Repeat Regions Detects Circulating Cell-free Echinococcus DNA.
BACKGROUND:Echinococcosis is a chronic zoonosis caused by tapeworms of the genus Echinococcus. Treatment of the disease is often expensive and complicated, sometimes requiring extensive surgery. Ultrasonographic imaging is currently the main technique for diagnosis, while immunological analysis prov...
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ftdoajarticles:oai:doaj.org/article:8b6d85568b9f44d9b0b6501db0d06e46 2023-05-15T15:08:04+02:00 Targeted Sequencing of Genomic Repeat Regions Detects Circulating Cell-free Echinococcus DNA. Zhengqing Wan Xiaoqing Peng Lu Ma Qingshan Tian Shizheng Wu Junqi Li Jie Ling Weigang Lv Binrong Ding Jieqiong Tan Zhuohua Zhang 2020-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008147 https://doaj.org/article/8b6d85568b9f44d9b0b6501db0d06e46 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008147 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008147 https://doaj.org/article/8b6d85568b9f44d9b0b6501db0d06e46 PLoS Neglected Tropical Diseases, Vol 14, Iss 3, p e0008147 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008147 2022-12-31T11:50:06Z BACKGROUND:Echinococcosis is a chronic zoonosis caused by tapeworms of the genus Echinococcus. Treatment of the disease is often expensive and complicated, sometimes requiring extensive surgery. Ultrasonographic imaging is currently the main technique for diagnosis, while immunological analysis provides additional information. Confirmation still needs pathological analysis. However, these diagnostic techniques generally detect infection in late stages of the disease. An accurate, early and non-invasive molecular diagnostic method is still unavailable. METHODOLOGY/PRINCIPAL FINDINGS:We sequenced the cell-free DNA (cfDNA) from plasma of echinococcosis patients and confirmed the presence of Echinococcus DNA. To improve detection sensitivity, we developed a method based on targeted next-generation sequencing of repeat regions. Simulation experiments demonstrate that the targeted sequencing is sensitive enough to detect as little as 0.1% of an Echinococcus genome in 1 mL of plasma. Results obtained using patient plasma shows that the Area Under the Curve (AUC) of the method is 0.862, with a detection sensitivity of 62.50% and specificity of 100%, corresponding to a Youden-index of 0.625. CONCLUSIONS/SIGNIFICANCE:This study provides evidence that hydatid cysts release cfDNA fragments into patient plasma. Using the repeat region targeted sequencing method, highly specific detection of Echinococcus infection was achieved. This study paves a new avenue for potential non-invasive screening and diagnosis of echinococcosis. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 3 e0008147 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Zhengqing Wan Xiaoqing Peng Lu Ma Qingshan Tian Shizheng Wu Junqi Li Jie Ling Weigang Lv Binrong Ding Jieqiong Tan Zhuohua Zhang Targeted Sequencing of Genomic Repeat Regions Detects Circulating Cell-free Echinococcus DNA. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Echinococcosis is a chronic zoonosis caused by tapeworms of the genus Echinococcus. Treatment of the disease is often expensive and complicated, sometimes requiring extensive surgery. Ultrasonographic imaging is currently the main technique for diagnosis, while immunological analysis provides additional information. Confirmation still needs pathological analysis. However, these diagnostic techniques generally detect infection in late stages of the disease. An accurate, early and non-invasive molecular diagnostic method is still unavailable. METHODOLOGY/PRINCIPAL FINDINGS:We sequenced the cell-free DNA (cfDNA) from plasma of echinococcosis patients and confirmed the presence of Echinococcus DNA. To improve detection sensitivity, we developed a method based on targeted next-generation sequencing of repeat regions. Simulation experiments demonstrate that the targeted sequencing is sensitive enough to detect as little as 0.1% of an Echinococcus genome in 1 mL of plasma. Results obtained using patient plasma shows that the Area Under the Curve (AUC) of the method is 0.862, with a detection sensitivity of 62.50% and specificity of 100%, corresponding to a Youden-index of 0.625. CONCLUSIONS/SIGNIFICANCE:This study provides evidence that hydatid cysts release cfDNA fragments into patient plasma. Using the repeat region targeted sequencing method, highly specific detection of Echinococcus infection was achieved. This study paves a new avenue for potential non-invasive screening and diagnosis of echinococcosis. |
format |
Article in Journal/Newspaper |
author |
Zhengqing Wan Xiaoqing Peng Lu Ma Qingshan Tian Shizheng Wu Junqi Li Jie Ling Weigang Lv Binrong Ding Jieqiong Tan Zhuohua Zhang |
author_facet |
Zhengqing Wan Xiaoqing Peng Lu Ma Qingshan Tian Shizheng Wu Junqi Li Jie Ling Weigang Lv Binrong Ding Jieqiong Tan Zhuohua Zhang |
author_sort |
Zhengqing Wan |
title |
Targeted Sequencing of Genomic Repeat Regions Detects Circulating Cell-free Echinococcus DNA. |
title_short |
Targeted Sequencing of Genomic Repeat Regions Detects Circulating Cell-free Echinococcus DNA. |
title_full |
Targeted Sequencing of Genomic Repeat Regions Detects Circulating Cell-free Echinococcus DNA. |
title_fullStr |
Targeted Sequencing of Genomic Repeat Regions Detects Circulating Cell-free Echinococcus DNA. |
title_full_unstemmed |
Targeted Sequencing of Genomic Repeat Regions Detects Circulating Cell-free Echinococcus DNA. |
title_sort |
targeted sequencing of genomic repeat regions detects circulating cell-free echinococcus dna. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008147 https://doaj.org/article/8b6d85568b9f44d9b0b6501db0d06e46 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 3, p e0008147 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008147 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008147 https://doaj.org/article/8b6d85568b9f44d9b0b6501db0d06e46 |
op_doi |
https://doi.org/10.1371/journal.pntd.0008147 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
14 |
container_issue |
3 |
container_start_page |
e0008147 |
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1766339496220033024 |