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Incorporating temporal dynamics of mutations to enhance the prediction capability of antiretroviral therapy's outcome for HIV-1.
Di Teodoro, Giulia; Pirkl, Martin; Incardona, Francesca; Vicenti, Ilaria; Sönnerborg, Anders; Kaiser, Rolf; Palagi, Laura; Zazzi, Maurizio; Lengauer, Thomas.
Afiliação
  • Di Teodoro G; Department of Computer Control and Management Engineering Antonio Ruberti, Sapienza University of Rome, Rome 00185, Italy.
  • Pirkl M; EuResist Network, Rome 00152, Italy.
  • Incardona F; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne 50935, Germany.
  • Vicenti I; German Center for Infection Research (DZIF), Cologne 50935, Germany.
  • Sönnerborg A; EuResist Network, Rome 00152, Italy.
  • Kaiser R; Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy.
  • Palagi L; I-PRO, Rome 00152, Italy.
  • Zazzi M; Department of Medicine Huddinge, Karolinska Institutet, Division of Infectious Diseases, Stockholm 14152, Sweden.
  • Lengauer T; Department of Infectious Diseases, Karolinska University Hospital, Stockholm 14186, Sweden.
Bioinformatics ; 40(6)2024 Jun 03.
Article em En | MEDLINE | ID: mdl-38775719
ABSTRACT
MOTIVATION In predicting HIV therapy outcomes, a critical clinical question is whether using historical information can enhance predictive capabilities compared with current or latest available data analysis. This study analyses whether historical knowledge, which includes viral mutations detected in all genotypic tests before therapy, their temporal occurrence, and concomitant viral load measurements, can bring improvements. We introduce a method to weigh mutations, considering the previously enumerated factors and the reference mutation-drug Stanford resistance tables. We compare a model encompassing history (H) with one not using this information (NH).

RESULTS:

The H-model demonstrates superior discriminative ability, with a higher ROC-AUC score (76.34%) than the NH-model (74.98%). Wilcoxon test results confirm significant improvement of predictive accuracy for treatment outcomes through incorporating historical information. The increased performance of the H-model might be attributed to its consideration of latent HIV reservoirs, probably obtained when leveraging historical information. The findings emphasize the importance of temporal dynamics in acquiring mutations. However, our result also shows that prediction accuracy remains relatively high even when no historical information is available. AVAILABILITY AND IMPLEMENTATION This analysis was conducted using the Euresist Integrated DataBase (EIDB). For further validation, we encourage reproducing this study with the latest release of the EIDB, which can be accessed upon request through the Euresist Network.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por HIV / HIV-1 / Mutação Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por HIV / HIV-1 / Mutação Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article