ctDNAtools: An R package to work with sequencing data of circulating tumor DNA

Alkodsi, Amjad; Meriranta, Leo; Pasanen, Annika; Leppä, Sirpa

doi:10.1101/2020.01.27.912790

Cited by 2 publications

(3 citation statements)

References 14 publications

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“…iSNVs below 5% for Illumina and 10% for Nanopore that are not found at a higher frequency in at least one time point per patient are likely to be sequencing errors and were filtered out. Reads containing reference and alternative alleles for positions in the spike’s RBD were extracted from the BAM files using ctDNAtools [ 24 ]. The number of reads containing different combinations of alternative and reference alleles was then compiled to determine the frequencies of the possible haplotypes.…”

Section: Methodsmentioning

confidence: 99%

Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis

Fournelle,

Mostefai,

Brunet-Ratnasingham

et al. 2024

Viruses

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Throughout the SARS-CoV-2 pandemic, several variants of concern (VOCs) have been identified, many of which share recurrent mutations in the 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.

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Section: Methodsmentioning

confidence: 99%

Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis

Fournelle,

Mostefai,

Brunet-Ratnasingham

et al. 2024

Viruses

View full text Add to dashboard Cite

show abstract

Section: Intra-host Analysismentioning

confidence: 99%

“…Reads containing reference and alternative alleles for positions in the spike's RBD were extracted from the BAM files using ctDNAtools. 24 The number of reads containing different combinations of alternative and reference alleles was then compiled to determine the frequencies of the possible haplotypes. Finally, we would like to thank members of the Mila COVID19 Task Force for their camaraderie and valuable insight into data analysis strategies during the pandemic.…”

Section: Intra-host Analysismentioning

confidence: 99%

Intra-host viral populations of SARS-CoV-2 in immunosuppressed patients with hematologic cancers

Fournelle

Mostefai

Brunet-Ratnasingham

et al. 2022

Preprint

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Throughout the SARS-CoV-2 pandemic, several variants of concern (VOC) have been identified, many of which share recurrent mutations in the spike 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.

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ctDNAtools: An R package to work with sequencing data of circulating tumor DNA

Cited by 2 publications

References 14 publications

Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis

Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis

Intra-host viral populations of SARS-CoV-2 in immunosuppressed patients with hematologic cancers

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