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Fatima Mostefai

Doctorat - Université de Montréal
Superviseur⋅e principal⋅e

Publications

Refining SARS-CoV-2 Intra-host Variation by Leveraging Large-scale Sequencing Data
Fatima Mostefai
Jean-Christophe Grenier
Raphael Poujol
Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis
Dominique Fournelle
Fatima Mostefai
Elsa Brunet-Ratnasingham
Raphael Poujol
Jean-Christophe Grenier
José Héctor Gálvez
Amélie Pagliuzza
Inès Levade
Sandrine Moreira
Mehdi Benlarbi
Guillaume Beaudoin-Bussières
Gabrielle Gendron-Lepage
Catherine Bourassa
Alexandra Tauzin
Simon Grandjean Lapierre
Nicolas Chomont
Andrés Finzi
Daniel E. Kaufmann
Morgan Craig
Selection for immune evasion in SARS-CoV-2 revealed by high-resolution epitope mapping and sequence analysis
Arnaud N’Guessan
Senthilkumar Kailasam
Fatima Mostefai
Raphael Poujol
Jean-Christophe Grenier
Nailya Ismailova
Paola Contini
Raffaele De Palma
Carsten Haber
Volker Stadler
Guillaume Bourque
B. Jesse Shapiro
Jörg H. Fritz
Ciriaco A. Piccirillo
The race to understand immunopathology in COVID-19: Perspectives on the impact of quantitative approaches to understand within-host interactions
Sonia Gazeau
Xiaoyan Deng
Hsu Kiang Ooi
Fatima Mostefai
Jane Heffernan
Adrianne L. Jenner
Morgan Craig
Intra-host viral populations of SARS-CoV-2 in immunosuppressed patients with hematologic cancers
Dominique Fournelle
Fatima Mostefai
Elsa Brunet-Ratnasingham
Raphael Poujol
Jean-Christophe Grenier
José Héctor Gálvez
Amélie Pagliuzza
Inès Levade
Sandrine Moreira
Simon Grandjean Lapierre
Nicolas Chomont
Daniel E. Kaufmann
Morgan Craig
Throughout the SARS-CoV-2 pandemic, several variants of concern (VOC) have been identified, many of which share recurrent mutations in the s… (voir plus)pike protein’s receptor binding domain (RBD). This region coincides with known epitopes and can therefore have an impact on immune escape. Protracted infections in immunosuppressed patients have been hypothesized to lead to an enrichment of such mutations and therefore drive evolution towards VOCs. Here, we show that immunosuppressed patients with hematologic cancers develop distinct populations with immune escape mutations throughout the course of their infection. Notably, by investigating the co-occurrence of substitutions on individual sequencing reads in the RBD, we found quasispecies harboring mutations that confer resistance to known monoclonal antibodies (mAbs) such as S:E484K and S:E484A. Furthermore, we provide the first evidence for a viral reservoir based on intra-host phylogenetics. Our results on viral reservoirs can shed light on protracted infections interspersed with periods where the virus is undetectable as well as an alternative explanation for some long-COVID cases. Our findings also highlight that protracted infections should be treated with combination therapies rather than by a single mAbs to clear pre-existing resistant mutations.
Population Genomics Approaches for Genetic Characterization of SARS-CoV-2 Lineages
Fatima Mostefai
I. Gamache
Arnaud N’Guessan
Justin Pelletier
Jessie Huang
Carmen Lia Murall
Ahmad Pesaranghader
Vanda Gaonac'h-Lovejoy
David J. Hamelin
Raphael Poujol
Jean-Christophe Grenier
Martin W. Smith
Étienne Caron
Morgan Craig
Smita Krishnaswamy
B. Jesse Shapiro
The genome of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19)… (voir plus), has been sequenced at an unprecedented scale leading to a tremendous amount of viral genome sequencing data. To assist in tracing infection pathways and design preventive strategies, a deep understanding of the viral genetic diversity landscape is needed. We present here a set of genomic surveillance tools from population genetics which can be used to better understand the evolution of this virus in humans. To illustrate the utility of this toolbox, we detail an in depth analysis of the genetic diversity of SARS-CoV-2 in first year of the COVID-19 pandemic. We analyzed 329,854 high-quality consensus sequences published in the GISAID database during the pre-vaccination phase. We demonstrate that, compared to standard phylogenetic approaches, haplotype networks can be computed efficiently on much larger datasets. This approach enables real-time lineage identification, a clear description of the relationship between variants of concern, and efficient detection of recurrent mutations. Furthermore, time series change of Tajima's D by haplotype provides a powerful metric of lineage expansion. Finally, principal component analysis (PCA) highlights key steps in variant emergence and facilitates the visualization of genomic variation in the context of SARS-CoV-2 diversity. The computational framework presented here is simple to implement and insightful for real-time genomic surveillance of SARS-CoV-2 and could be applied to any pathogen that threatens the health of populations of humans and other organisms.
Population Genomics Approaches for Genetic Characterization of SARS-CoV-2 Lineages
Fatima Mostefai
Isabel Gamache
Arnaud N’Guessan
Justin Pelletier
Jessie Huang
Carmen Lia Murall
Ahmad Pesaranghader
Vanda Gaonac'h-Lovejoy
David J. Hamelin
Raphael Poujol
Jean-Christophe Grenier
Martin Smith
Etienne Caron
Morgan Craig
Smita Krishnaswamy
B. Jesse Shapiro
Patient health records and whole viral genomes from an early SARS-CoV-2 outbreak in a Quebec hospital reveal features associated with favorable outcomes
Bastien Paré
Marieke Rozendaal
Sacha Morin
Léa Kaufmann
Shawn M. Simpson
Raphael Poujol
Fatima Mostefai
Jean-Christophe Grenier
Henry Xing
Miguelle Sanchez
Ariane Yechouron
Ronald Racette
Ivan Pavlov
Martin Smith
Data-driven approaches for genetic characterization of SARS-CoV-2 lineages
Fatima Mostefai
Isabel Gamache
Jessie Huang
Arnaud N’Guessan
Justin Pelletier
Ahmad Pesaranghader
David J. Hamelin
Carmen Lia Murall
Raphael Poujol
Jean-Christophe Grenier
Martin Smith
Etienne Caron
Morgan Craig
Jesse Shapiro
Smita Krishnaswamy
The genome of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19)… (voir plus), has been sequenced at an unprecedented scale, leading to a tremendous amount of viral genome sequencing data. To understand the evolution of this virus in humans, and to assist in tracing infection pathways and designing preventive strategies, we present a set of computational tools that span phylogenomics, population genetics and machine learning approaches. To illustrate the utility of this toolbox, we detail an in depth analysis of the genetic diversity of SARS-CoV-2 in first year of the COVID-19 pandemic, using 329,854 high-quality consensus sequences published in the GISAID database during the pre-vaccination phase. We demonstrate that, compared to standard phylogenetic approaches, haplotype networks can be computed efficiently on much larger datasets, enabling real-time analyses. Furthermore, time series change of Tajima’s D provides a powerful metric of population expansion. Unsupervised learning techniques further highlight key steps in variant detection and facilitate the study of the role of this genomic variation in the context of SARS-CoV-2 infection, with Multiscale PHATE methodology identifying fine-scale structure in the SARS-CoV-2 genetic data that underlies the emergence of key lineages. The computational framework presented here is useful for real-time genomic surveillance of SARS-CoV-2 and could be applied to any pathogen that threatens the health of worldwide populations of humans and other organisms.
Genomic epidemiology and associated clinical outcomes of a SARS-CoV-2 outbreak in a general adult hospital in Quebec
Bastien Paré
Marieke Rozendaal
Sacha Morin
Raphael Poujol
Fatima Mostefai
Jean-Christophe Grenier
Léa Kaufmann
Henry Xing
Miguelle Sanchez
Ariane Yechouron
Ronald Racette
Ivan Pavlov
Martin Smith