Fatima Mostefai

2024-05-01

bioRxiv (preprint)

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

2024-02-23

Viruses (published)

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

2023-07-13

iScience (published)

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

2023-01-01

ImmunoInformatics (published)

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… (see more)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.

2022-10-20

bioRxiv (preprint)

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)… (see more), 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.

2022-02-21

Frontiers in Medicine (published)

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

2022-02-21

Frontiers in Medicine (published)

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

Shawn M. Simpson

Jean-Christophe Grenier

Léa Kaufmann

Henry Xing

Miguelle Sanchez

Ariane Yechouron

Ronald Racette

Ivan Pavlov

Martin Smith

2021-12-02

PLoS ONE (published)

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

2021-12-02

PLoS ONE (published)

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)… (see more), 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.

2021-09-29

bioRxiv (preprint)