publications

2024

1. Factors shaping vaginal microbiota long-term community dynamics in young adult women

   Tsukushi Kamiya, Nicolas Tessandier, Baptiste Elie, and 17 more authors

   medRxiv 2024

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   The vaginal microbiota is categorised into five main community state types (CST) that are known to affect women’s health. Yet, there is a notable paucity of high-resolution follow-up studies lasting several months, which are required to interrogate the long-term dynamics and associations with demographic and behavioural covariates. Here, we present a high-resolution longitudinal cohort of 125 women followed for a median duration of 8.6 months, providing 11 samples per woman. Using a hierarchical Bayesian Markov model, we characterised the patterns of CST persistence and transition, simultaneously estimated the impact of 16 covariates and quantified individual variability among women. We showed that ‘optimal’ (CSTs I, II, and V) and ‘sub-optimal’ (CST III) communities are more stable in time than ‘non-optimal’ (CST IV) ones. Furthermore, we found that some covariates — most notably alcohol consumption — impacted the probability of shifting from one CST to another. We performed counterfactual simulations to confirm that alterations of key covariates, such as alcohol consumption, could shape the prevalence of different microbiota communities in the population. Finally, our analyses indicated that there is a relatively canalised pathway leading to the deterioration of vaginal microbiota communities, whereas the paths to recovery can be highly individualised among women. In addition to providing one of the first insights into vaginal microbiota dynamics over a year, our study showcases a novel application of a hierarchical Bayesian Markov model to clinical cohort data with many covariates. Our findings pave the way for an improved mechanistic understanding of microbial dynamics in the vaginal environment and the development of novel preventative and therapeutic strategies to improve vaginal health.Competing Interest StatementJReynes reports personal fees from Gilead (consulting and payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events), Janssen (payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events), Merck (payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events), Theratechnologies (payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events), and ViiV Healthcare (consulting and payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events) and support for attending meetings and/or travel from Gilead and Pfizer, outside of the submitted work. JRavel is co-founder of LUCA Biologics, a biotechnology company focusing on translating microbiome research into live biotherapeutics drugs for women’s health. He is Editor-in-Chief at Microbiome. All the other authors do not report any conflict of interest. Clinical Protocols http://dx.doi.org/10.1136/bmjopen-2018-025129 Funding StatementThis project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 648963, to SA). The authors acknowledge further support from the Fondation pour la Recherche Medicale (to TK), the Agence Nationale de la Recherche contre le SIDA (ANRS-MIE, to NT and OS), and the MemoLife Labex (to BE).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The PAPCLEAR study was promoted by the CHU of Montpellier (France). This study has been approved by the Comité de Protection des Personnes (CPP) Sud Mediterranée I (reference number 2016-A00712-49); by the Comité Consultatif sur le Traitement de l’Information en matière de Recherche dans le domaine de la Santé (reference number 16.504); by the Commission Nationale Informatique et Libertés (reference number MMS/ ABD/ AR1612278, decision number DR-2016-488), by the Agence Nationale de Securité du Medicament et des Produits de Sante (reference 20160072000007), and is registered at ClinicalTrials.gov under the ID NCT02946346.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll the data analysed in the present work will be made available online after peer-review.

2023

1. HPV detection patterns in young women from the PAPCLEAR longitudinal study: implications for HPV screening policies

   Thomas Beneteau, Soraya Groc, Carmen Lia Murall, and 17 more authors

   medRxiv 2023

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   Objectives HPV infections are ubiquitous. For most infections, we lose track of the presence of the virus in host in less than three years after the start of infection. The mechanisms regulating the persistence of HPV infection are still partially understood. In this work, we focus on incident HPV detection in young women and we characterise the dynamics of these infections and evaluate the effect of genotype and host socio-economic factors on the duration of HPV detection and time between detection.Methods We investigated human papillomavirus (HPV) genotype detection patterns in 182 young women in Montpellier, France. We relied on SPF10-LiPA25 screening assay for the simultaneous de-tection of 25 HPV genotypes. We used survival analysis tools with frailty effects to investigate the contribution of viral and host factors to variations in the time of HPV detectability, time of first incident detection, and time before re-detection.Results Women of the PAPCLEAR cohort experienced numerous positive HPV events, including frequent redetection of the same genotype. We retrieve classical results that HR-genotypes are detected for longer duration than LR-genotypes. HR-genotypes were also more liekly to be detected than LR-genotypes during the follow-up. The number of lifetime sexual partner was strongly associated with increased risk of new positive detection while vaccination was related to a lower risk of displaying incident infections. Covariates related to socio-economic difficulties were associated with longer duration of HPV positivity.Conclusions Young women display numerous event of HPV detection, with frequent codetections of multiple genotypes at the same time and redetection of the same type after periods of no detection. These new detection are almost certainly the result of new acquisition from sexual partners, with little evidence of re-emergence of latent infections. A better characterisation of transient infections might help unveil doubts and misconception on HPV physiopathology, favouring adherence to preventive policies.Competing Interest StatementJ. R. reports personal fees from Gilead (consulting and payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events), Janssen (payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events), Merck (payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events), Theratechnologies (payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events), and ViiV Healthcare (consulting and payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events) and support for attending meetings and/or travel from Gilead and Pfizer, outside of the submitted work. All the other authors do not report any conflict of interest or personal relationships that could have appeared to influence the work reported in this paper.Funding StatementTB is funded by la Ligue contre le Cancer (grant No TAKX21133). This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 648963 to SA). The sponsor had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The PAPCLEAR trial was promoted by the Centre Hospitalier Universitaire de Montpellier and approved by the Comité de Protection des Personnes (CPP) Sud Méditerranée I on 11 May 2016 (CPP number 16 42, reference number ID RCB 2016A00712-49); by the Comité Consultatif sur le Traitement de l’Information en matière de Recherche dans le domaine de la Santé on 12 July 2016 (reference number 16.504); and by the Commission Nationale Informatique et Libertés on 16 December 2016 (reference number MMS/ABD/AR1612278, decision number DR-2016488). This trial was authorised by the Agence Nationale de Sécurité du Médicament et des Produits de Santé on 20 July 2016 (reference 20160072000007). The ClinicalTrials.gov identifier is NCT02946346. All participants provided written informed consent.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesThe raw data and R scripts used will be deposited on the Zenodo server upon publication.

2. Viral and immune dynamics of HPV genital infections in young women

   Nicolas Tessandier, Baptiste Elie, Vanina Boué, and 32 more authors

   May 2023

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2022

1. Non-Markovian modelling highlights the importance of age structure on Covid-19 epidemiological dynamics

   Bastien Reyné, Quentin Richard, Christian Selinger, and 3 more authors

   Mathematical Modelling of Natural Phenomena May 2022

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2. Concomitant and productive genital infections by HSV-2 and HPV in two young women: A case report

   Ilkay Başak Uysal, Vanina Boué, Carmen Lia Murall, and 19 more authors

   IDCases May 2022

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3. Epidemiological and clinical insights from SARS-CoV-2 RT-PCR crossing threshold values, France, January to November 2020

   Samuel Alizon, Christian Selinger, Mircea T Sofonea, and 25 more authors

   Eurosurveillance Feb 2022

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4. The source of individual heterogeneity shapes infectious disease outbreaks

   Baptiste Elie, Christian Selinger, and Samuel Alizon

   Proceedings of the Royal Society B: Biological Sciences May 2022

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5. Does exposure to different menstrual products affect the vaginal environment?

   Nicolas Tessandier, Ilkay Başak Uysal, Baptiste Elie, and 22 more authors

   Molecular Ecology Oct 2022

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2021

1. Predicting COVID-19 incidence in French hospitals using human contact network analytics

   Christian Selinger, Marc Choisy, and Samuel Alizon

   International Journal of Infectious Diseases Oct 2021

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2. Episome partitioning and symmetric cell divisions: Quantifying the role of random events in the persistence of HPV infections

   Thomas Beneteau, Christian Selinger, Mircea T. Sofonea, and 1 more author

   PLOS Computational Biology Sep 2021

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3. Reconstructing contact network structure and cross-immunity patterns from multiple infection histories

   Christian Selinger, and Samuel Alizon

   PLOS Computational Biology Sep 2021

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4. Analysing different exposures identifies that wearing masks and establishing COVID-19 areas reduce secondary-attack risk in aged-care facilities

   Bastien Reyné, Christian Selinger, Mircea T Sofonea, and 6 more authors

   International Journal of Epidemiology Jun 2021

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5. Memory is key in capturing COVID-19 epidemiological dynamics

   Mircea T. Sofonea, Bastien Reyné, Baptiste Elie, and 4 more authors

   Epidemics Jun 2021

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6. Optimizing the early detection of low pathogenic avian influenza H7N9 virus in live bird markets

   Claire Guinat, Damian Tago, Tifenn Corre, and 9 more authors

   Journal of The Royal Society Interface May 2021

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7. Cytokine response following perturbation of the cervicovaginal milieu during HPV genital infection

   Christian Selinger, Massilva Rahmoun, Carmen Lia Murall, and 10 more authors

   Immunologic Research Apr 2021

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8. Detecting Rapid Spread of SARS-CoV-2 Variants, France, January 26–February 16, 2021

   Stéphanie Haim-Boukobza, Bénédicte Roquebert, Sabine Trombert-Paolantoni, and 7 more authors

   Emerging Infectious Diseases May 2021

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2020

1. HPV cervical infections and serological status in vaccinated and unvaccinated women

   Carmen Lı́a Murall, Bastien Reyné, Christian Selinger, and 18 more authors

   Vaccine Dec 2020

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2. Épidémiologie mathématique et modélisation de la pandémie de Covid-19 : enjeux et diversité

   Ramsès Djidjou-Demasse, Christian Selinger, and Mircea T. Sofonea

   Revue Francophone des Laboratoires Nov 2020

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2019

1. Natural history, dynamics, and ecology of human papillomaviruses in genital infections of young women: protocol of the PAPCLEAR cohort study

   Carmen Lı́a Murall, Massilva Rahmoun, Christian Selinger, and 32 more authors

   BMJ Open Jun 2019

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2. The future of a partially effective HIV vaccine: assessing limitations at the population level

   Christian Selinger, Dobromir T. Dimitrov, Philip A. Welkhoff, and 1 more author

   International Journal of Public Health Apr 2019

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3. Targeting and vaccine durability are key for population-level impact and cost-effectiveness of a pox-protein HIV vaccine regimen in South Africa

   Christian Selinger, Anna Bershteyn, Dobromir T. Dimitrov, and 7 more authors

   Vaccine Apr 2019

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2018

1. Assessing the stability of polio eradication after the withdrawal of oral polio vaccine

   Michael Famulare, Christian Selinger, Kevin A. McCarthy, and 2 more authors

   PLOS Biology Apr 2018

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2. Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy

   Ameya R. Kirtane, Omar Abouzid, Daniel Minahan, and 22 more authors

   Nature Communications Jan 2018

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2016

1. Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism

   Jennifer Tisoncik-Go, David J. Gasper, Jennifer E. Kyle, and 22 more authors

   Cell Host & Microbe Feb 2016

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2. The 1918 Influenza Virus PB2 Protein Enhances Virulence through the Disruption of Inflammatory and Wnt-Mediated Signaling in Mice

   Adriana Forero, Jennifer Tisoncik-Go, Tokiko Watanabe, and 12 more authors

   Journal of Virology Mar 2016

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2014

1. Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates

   Christian Selinger, Jennifer Tisoncik-Go, Vineet D Menachery, and 7 more authors

   BMC Genomics Dec 2014

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2. Multiple Low-Dose Challenges in a Rhesus Macaque AIDS Vaccine Trial Result in an Evolving Host Response That Affects Protective Outcome

   Christian Selinger, Natasa Strbo, Louis Gonzalez, and 8 more authors

   Clinical and Vaccine Immunology Oct 2014

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3. MicroRNAs Establish Robustness and Adaptability of a Critical Gene Network to Regulate Progenitor Fate Decisions during Cortical Neurogenesis

   Tanay Ghosh, Julieta Aprea, Jeannette Nardelli, and 14 more authors

   Cell Reports Jun 2014

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2013

1. Mathematical models of viral latency

   Christian Selinger, and Michael G Katze

   Current Opinion in Virology Aug 2013

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2011

1. Zeta function regularized Laplacian on the smooth Wasserstein space above the unit circle

   Christian Selinger

   Theory Stoch. Process. Aug 2011

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2009

1. Brenier’s solution to the optimal transport problem in the Euclidean case, polar factorization of vector-valued maps

   Christian Selinger

   Arbeitsgemeinschaft Mathematisches Forschungsinstitut Oberwolfach: Optimal Transport and Geometry Aug 2009

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