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Fatima Mostefai

Alumni

Publications

Machine learning-enhanced immunopeptidomics applied to T-cell epitope discovery for COVID-19 vaccines
Kevin A. Kovalchik
David J. Hamelin
Peter Kubiniok
Benoîte Bourdin
Fatima Mostefai
Raphaël Poujol
Bastien Paré
Shawn M. Simpson
John Sidney
Éric Bonneil
Mathieu Courcelles
Sunil Kumar Saini
Mohammad Shahbazy
Saketh Kapoor
Vigneshwar Rajesh
Maya Weitzen
Jean-Christophe Grenier
Bayrem Gharsallaoui
Loïze Maréchal
Zhaoguan Wu … (voir 9 de plus)
Christopher Savoie
Alessandro Sette
Pierre Thibault
Isabelle Sirois
Martin A. Smith
Hélène Decaluwe
Julie G. Hussin
Mathieu Lavallée-Adam
Etienne Caron
Next-generation T-cell-directed vaccines for COVID-19 focus on establishing lasting T-cell immunity against current and emerging SARS-CoV-2 … (voir plus)variants. Precise identification of conserved T-cell epitopes is critical for designing effective vaccines. Here we introduce a comprehensive computational framework incorporating a machine learning algorithm—MHCvalidator—to enhance mass spectrometry-based immunopeptidomics sensitivity. MHCvalidator identifies unique T-cell epitopes presented by the B7 supertype, including an epitope from a + 1-frameshift in a truncated Spike antigen, supported by ribosome profiling. Analysis of 100,512 COVID-19 patient proteomes shows Spike antigen truncation in 0.85% of cases, revealing frameshifted viral antigens at the population level. Our EpiTrack pipeline tracks global mutations of MHCvalidator-identified CD8 + T-cell epitopes from the BNT162b4 vaccine. While most vaccine epitopes remain globally conserved, an immunodominant A*01-associated epitope mutates in Delta and Omicron variants. This work highlights SARS-CoV-2 antigenic features and emphasizes the importance of continuous adaptation in T-cell vaccine development.
2024-11-27
Nature Communications (publié)
doi.org
Refining SARS-CoV-2 intra-host variation by leveraging large-scale sequencing data
Fatima Mostefai
Jean-Christophe Grenier
Raphaël Poujol
Julie Hussin
Understanding viral genome evolution during host infection is crucial for grasping viral diversity and evolution. Analyzing intra-host singl… (voir plus)e nucleotide variants (iSNVs) offers insights into new lineage emergence, which is important for predicting and mitigating future viral threats. Despite next-generation sequencing’s potential, challenges persist, notably sequencing artifacts leading to false iSNVs. We developed a workflow to enhance iSNV detection in large NGS libraries, using over 130 000 SARS-CoV-2 libraries to distinguish mutations from errors. Our approach integrates bioinformatics protocols, stringent quality control, and dimensionality reduction to tackle batch effects and improve mutation detection reliability. Additionally, we pioneer the application of the PHATE visualization approach to genomic data and introduce a methodology that quantifies how related groups of data points are represented within a two-dimensional space, enhancing clustering structure explanation based on genetic similarities. This workflow advances accurate intra-host mutation detection, facilitating a deeper understanding of viral diversity and evolution.
2024-09-27
NAR Genomics and Bioinformatics (publié)
doi.org
Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis
Dominique Fournelle
Fatima Mostefai
Elsa Brunet-Ratnasingham
Raphaël 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
Julie G. Hussin
Throughout the SARS-CoV-2 pandemic, several variants of concern (VOCs) have been identified, many of which share recurrent mutations in the … (voir plus)spike glycoprotein’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 present the case of an immunosuppressed patient that developed 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. These mutations were acquired without the patient being treated with mAbs nor convalescent sera and without them developing a detectable immune response to the virus. We also provide additional evidence for a viral reservoir based on intra-host phylogenetics, which led to a viral substrain that evolved elsewhere in the patient’s body, colonizing their upper respiratory tract (URT). The presence of SARS-CoV-2 viral reservoirs can shed light on protracted infections interspersed with periods where the virus is undetectable, and potential explanations for long-COVID cases.
2024-02-22
Viruses (publié)
doi.org
Selection for immune evasion in SARS-CoV-2 revealed by high-resolution epitope mapping and sequence analysis
Arnaud N’Guessan
Senthilkumar Kailasam
Fatima Mostefai
Raphaël Poujol
Jean-Christophe Grenier
Nailya Ismailova
Paola Contini
Raffaele De Palma
Carsten Haber
Volker Stadler
Guillaume Bourque
Julie G. Hussin
B. Jesse Shapiro
Jörg H. Fritz
Ciriaco A. Piccirillo
2023-07-31
iScience (publié)
doi.org
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
Julie G Hussin
Jane Heffernan
Adrianne L. Jenner
Morgan Craig
2022-12-31
ImmunoInformatics (publié)
doi.org
Intra-host viral populations of SARS-CoV-2 in immunosuppressed patients with hematologic cancers
Dominique Fournelle
Fatima Mostefai
Elsa Brunet-Ratnasingham
Raphaël Poujol
Jean-Christophe Grenier
José Héctor Gálvez
Amélie Pagliuzza
Inès Levade
Sandrine Moreira
Simon Grandjean Lapierre
Nicolas Chomont
Daniel E. Kaufmann
Morgan Craig
Julie G. Hussin
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.
2022-10-19
bioRxiv (prépublication)
doi.org
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
Raphaël Poujol
Jean-Christophe Grenier
Martin Smith
Etienne Caron
Morgan Craig
Guy Wolf
Smita Krishnaswamy
B. Jesse Shapiro
Julie G. Hussin
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.
2022-02-20
Frontiers in Medicine (publié)
doi.org
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
Raphaël Poujol
Fatima Mostefai
Shawn M. Simpson
Jean-Christophe Grenier
Léa Kaufmann
Henry Xing
Miguelle Sanchez
Ariane Yechouron
Ronald Racette
Julie G. Hussin
Guy Wolf
Ivan Pavlov
Martin A. Smith
The first confirmed case of COVID-19 in Quebec, Canada, occurred at Verdun Hospital on February 25, 2020. A month later, a localized outbrea… (voir plus)k was observed at this hospital. We performed tiled amplicon whole genome nanopore sequencing on nasopharyngeal swabs from all SARS-CoV-2 positive samples from 31 March to 17 April 2020 in 2 local hospitals to assess the viral diversity of the outbreak. We report 264 viral genomes from 242 individuals (both staff and patients) with associated clinical features and outcomes, as well as longitudinal samples, technical replicates and the first publicly disseminated SARS-CoV-2 genomes in Quebec. Viral lineage assessment identified multiple subclades in both hospitals, with a predominant subclade in the Verdun outbreak, indicative of hospital-acquired transmission. Dimensionality reduction identified two subclades that evaded supervised lineage assignment methods, including Pangolin, and identified certain symptoms (headache, myalgia and sore throat) that are significantly associated with favorable patient outcomes. We also address certain limitations of standard SARS-CoV-2 bioinformatics procedures, notably when presented with multiple viral haplotypes.
2021-12-01
PLOS ONE (publié)
doi.org
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 Hamelin
Carmen Lia Murall
Raphaël Poujol
Jean-Christophe Grenier
Martin Smith
Etienne Caron
Morgan Craig
Jesse Shapiro
Guy Wolf
Smita Krishnaswamy
Julie G. Hussin
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.
2021-09-28
BioRxiv (prépublication)
doi.org