HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection
HIV-1 genetic diversity can be used to infer time since infection (TSI) and infection recency. We adapted this approach for HCV and identified genomic regions with informative diversity. We included 72 HCV/HIV-1 coinfected participants of the Swiss HIV Cohort Study, for whom reliable estimates of in...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/11/1241 |
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| author | Louisa A. Carlisle Teja Turk Karin J. Metzner Herbert A. Mbunkah Cyril Shah Jürg Böni Michael Huber Dominique L. Braun Jan Fehr Luisa Salazar-Vizcaya Andri Rauch Sabine Yerly Aude Nguyen Matthias Cavassini Marcel Stoeckle Pietro Vernazza Enos Bernasconi Huldrych F. Günthard Roger D. Kouyos |
| author_facet | Louisa A. Carlisle Teja Turk Karin J. Metzner Herbert A. Mbunkah Cyril Shah Jürg Böni Michael Huber Dominique L. Braun Jan Fehr Luisa Salazar-Vizcaya Andri Rauch Sabine Yerly Aude Nguyen Matthias Cavassini Marcel Stoeckle Pietro Vernazza Enos Bernasconi Huldrych F. Günthard Roger D. Kouyos |
| author_sort | Louisa A. Carlisle |
| collection | DOAJ |
| description | HIV-1 genetic diversity can be used to infer time since infection (TSI) and infection recency. We adapted this approach for HCV and identified genomic regions with informative diversity. We included 72 HCV/HIV-1 coinfected participants of the Swiss HIV Cohort Study, for whom reliable estimates of infection date and viral sequences were available. Average pairwise diversity (APD) was calculated over each codon position for the entire open reading frame of HCV. Utilizing cross validation, we evaluated the correlation of APD with TSI, and its ability to infer TSI via a linear model. We additionally studied the ability of diversity to classify infections as recent (infected for <1 year) or chronic, using receiver-operator-characteristic area under the curve (ROC-AUC) in 50 patients whose infection could be unambiguously classified as either recent or chronic. Measuring HCV diversity over third or all codon positions gave similar performances, and notable improvement over first or second codon positions. APD calculated over the entire genome enabled classification of infection recency (ROC-AUC = 0.76). Additionally, APD correlated with TSI (R<sup>2</sup> = 0.33) and could predict TSI (mean absolute error = 1.67 years). Restricting the region over which APD was calculated to <i>E2</i>-<i>NS2</i> further improved accuracy (ROC-AUC = 0.85, R<sup>2</sup> = 0.54, mean absolute error = 1.38 years)<b>.</b> Genetic diversity in HCV correlates with TSI and is a proxy for infection recency and TSI, even several years post-infection. |
| first_indexed | 2024-03-10T15:11:03Z |
| format | Article |
| id | doaj.art-855b99d7b3dd444d89e21632210febe5 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T15:11:03Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-855b99d7b3dd444d89e21632210febe52023-11-20T19:18:28ZengMDPI AGViruses1999-49152020-10-011211124110.3390/v12111241HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since InfectionLouisa A. Carlisle0Teja Turk1Karin J. Metzner2Herbert A. Mbunkah3Cyril Shah4Jürg Böni5Michael Huber6Dominique L. Braun7Jan Fehr8Luisa Salazar-Vizcaya9Andri Rauch10Sabine Yerly11Aude Nguyen12Matthias Cavassini13Marcel Stoeckle14Pietro Vernazza15Enos Bernasconi16Huldrych F. Günthard17Roger D. Kouyos18Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, CH-8091 Zurich, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, CH-8091 Zurich, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, CH-8091 Zurich, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, CH-8091 Zurich, SwitzerlandInstitute of Medical Virology, University of Zurich, CH-8057 Zurich, SwitzerlandInstitute of Medical Virology, University of Zurich, CH-8057 Zurich, SwitzerlandInstitute of Medical Virology, University of Zurich, CH-8057 Zurich, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, CH-8091 Zurich, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, CH-8091 Zurich, SwitzerlandDepartment of Infectious Diseases, Bern University Hospital, University of Bern, CH-3010 Bern, SwitzerlandDepartment of Infectious Diseases, Bern University Hospital, University of Bern, CH-3010 Bern, SwitzerlandLaboratory of Virology, Division of Infectious Diseases, Geneva University Hospital, University of Geneva, CH-1205 Geneva, SwitzerlandLaboratory of Virology, Division of Infectious Diseases, Geneva University Hospital, University of Geneva, CH-1205 Geneva, SwitzerlandDivision of Infectious Diseases, Lausanne University Hospital, CH-1011 Lausanne, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, CH-4031 Basel, SwitzerlandDivision of Infectious Diseases, Cantonal Hospital St Gallen, CH-9007 St. Gallen, SwitzerlandDivision of Infectious Diseases, Regional Hospital Lugano, CH-6900 Lugano, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, CH-8091 Zurich, SwitzerlandDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, CH-8091 Zurich, SwitzerlandHIV-1 genetic diversity can be used to infer time since infection (TSI) and infection recency. We adapted this approach for HCV and identified genomic regions with informative diversity. We included 72 HCV/HIV-1 coinfected participants of the Swiss HIV Cohort Study, for whom reliable estimates of infection date and viral sequences were available. Average pairwise diversity (APD) was calculated over each codon position for the entire open reading frame of HCV. Utilizing cross validation, we evaluated the correlation of APD with TSI, and its ability to infer TSI via a linear model. We additionally studied the ability of diversity to classify infections as recent (infected for <1 year) or chronic, using receiver-operator-characteristic area under the curve (ROC-AUC) in 50 patients whose infection could be unambiguously classified as either recent or chronic. Measuring HCV diversity over third or all codon positions gave similar performances, and notable improvement over first or second codon positions. APD calculated over the entire genome enabled classification of infection recency (ROC-AUC = 0.76). Additionally, APD correlated with TSI (R<sup>2</sup> = 0.33) and could predict TSI (mean absolute error = 1.67 years). Restricting the region over which APD was calculated to <i>E2</i>-<i>NS2</i> further improved accuracy (ROC-AUC = 0.85, R<sup>2</sup> = 0.54, mean absolute error = 1.38 years)<b>.</b> Genetic diversity in HCV correlates with TSI and is a proxy for infection recency and TSI, even several years post-infection.https://www.mdpi.com/1999-4915/12/11/1241hepatitis C virus infectioninfection recencygenetic variationsequence analysisviral genomics |
| spellingShingle | Louisa A. Carlisle Teja Turk Karin J. Metzner Herbert A. Mbunkah Cyril Shah Jürg Böni Michael Huber Dominique L. Braun Jan Fehr Luisa Salazar-Vizcaya Andri Rauch Sabine Yerly Aude Nguyen Matthias Cavassini Marcel Stoeckle Pietro Vernazza Enos Bernasconi Huldrych F. Günthard Roger D. Kouyos HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection Viruses hepatitis C virus infection infection recency genetic variation sequence analysis viral genomics |
| title | HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection |
| title_full | HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection |
| title_fullStr | HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection |
| title_full_unstemmed | HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection |
| title_short | HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection |
| title_sort | hcv genetic diversity can be used to infer infection recency and time since infection |
| topic | hepatitis C virus infection infection recency genetic variation sequence analysis viral genomics |
| url | https://www.mdpi.com/1999-4915/12/11/1241 |
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