Biology subjects

Hamel, S.

Publications and source records attributed to Hamel, S..

6 recordsLinked to original sources

bioRxiv2026

gVCF2CNV: a scalable pipeline for CNV detection from whole-genome sequencing data

Motivation: Copy-number variants (CNVs) contribute to human disease and population trait variation. CNV detection from large whole-genome sequencing cohorts remains computationally demanding, as most methods require BAM or CRAM files. Genomic VCF (gVCF) files are smaller, routinely generated by standard variant-calling workflows, and contain the read depth and allelic information needed for CNV detection. However, gVCF files are not directly compatible with established CNV callers that rely on Log R Ratio (LRR) and B Allele Frequency (BAF) signals. Results: We present gVCF2CNV, a Nextflow pipeline that converts gVCF files into Log R Ratio and B Allele Frequency signals compatible with established CNV callers. Applied to 12,509 individuals from the SPARK cohort, gVCF2CNV generated signals at an average of 2.7 million SNV positions per individual and completed signal extraction in 4 hours using 192 CPUs. CNV calling with PennCNV and QuantiSNP identified candidate CNVs across a broad size range, with trio-based Mendelian precision reaching approximately 80% or higher for deletions of at least 30 kb and duplications of at least 5 kb. Application to 414,824 individuals from the All of Us cohort was completed in 96 hours, demonstrating feasibility at biobank scale. These results show that gVCF files can serve as a scalable input for CNV detection in large WGS cohorts. Availability and Implementation: gVCF2CNV is available at https://github.com/JacquemontLab/gVCF2CNV, implemented as a Nextflow pipeline with Perl and Python components, supported on Linux. Contact: mame.seynabou.diop@umontreal.ca

bioinformatics↗

bioRxiv2026

MCNV2 (Mendelian CNV Validation): Mendelian Precision for CNV quality assessment

SummaryDetection of copy number variations from genomic sequencing and array data is prone to high false-positive rates. Distinguishing true variation from false positives remains challenging as quality metrics depend on technologies used, the quality of the data, and the calling algorithm. Mendelian inheritance in parent-offspring trios offers a powerful method to detect false positives, yet no tool exists to systematically compute, explore, optimize, and interpret the precision of CNV calls accordingly. Here we present Mendelian CNV Validation (MCNV2), an R package implementing Mendelian Precision (MP), as a reproducible metric for standardized CNV quality assessment. MCNV2 provides a command-line interface for pipeline integration and an interactive Shiny application for real-time exploration of MP across CNV types, size categories, and quality metrics. Availability and ImplementationMCNV2 is available at https://github.com/JacquemontLab/MCNV2-Mendelian-CNV-Validation. Contactmame.seynabou.diop@umontreal.ca Supplementary InformationSupplementary information are available at https://mcnv2-mendelian-cnv-validation.readthedocs.io/en/latest/

genetics↗

bioRxiv2025

TREM2 macrophages are associated with enhanced response to PD-1 blockade in human hepatocellular carcinoma

Macrophages are known to dampen tumor immunity. However, identifying druggable targets that modulate these cells to improve existing immunotherapies has been limited by a dearth of studies identifying macrophages that associate with pathological response to immune checkpoint blockade. To fulfill this unmet clinical need, we leveraged transcriptional and spatial profiling of specimens collected from a Phase II clinical trial studying neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC). We determined that the intratumoral abundance of TREM2-expressing macrophages and serological levels of soluble TREM2 are elevated in patients who responded to PD-1 blockade, compared to non-responders. We validated these findings in a second HCC cohort and in the IMbrave150 trial. These highlight the robust potential for TREM2 macrophages to predict therapeutic responses of HCC to immunotherapy. Therefore, our study provides a novel basis for the use of TREM2 macrophages to strategize treatment for patients with HCC to maximize therapeutic benefit.

immunology↗

bioRxiv2025

MARQO pipeline resolves multiparametric cellular and spatial organization in cancer tissue lesions

Multiplex immunostaining analysis remains fragmented, underperforming, and labor-intensive despite tissue proteomic methodologies achieving ever-increasing marker complexity. Here we propose an open-source, semi-supervised automated pipeline that streamlines start-to-finish, single-cell resolution analysis of whole-slide tissue, named Multiplex-imaging Analysis, Registration, Quantification, and Overlaying (MARQO). We compared and validated MARQO using Multiplex Immunohistochemical Consecutive Staining on a Single Slide (MICSSS) using human tumor and adjacent normal tissue samples. Performance was compared with manually-curated pathologist determinations and quantification of multiple markers. We also optimized MARQO to analyze diverse tissue sizes (whole tissue, biopsy, tissue microarray) and staining approaches (singleplex immunohistochemistry, 20-color multiplex immunofluorescence) to determine marker co-expression patterns in multiple human solid cancer types. Lastly, we validated CD8 T cell enrichment in hepatocellular carcinoma responders to neoadjuvant cemiplimab in a phase II clinical trial, further demonstrating MARQOs ability to provide spatially-resolved in situ mechanisms by providing multiplex whole-slide single-cell resolution data.

immunology↗

bioRxiv2023

Climate, caribou and human needs linked by analysis of Indigenous and scientific knowledge

Migratory tundra caribou are ecologically and culturally critical in the circumpolar North. However, they are declining almost everywhere in North America, likely due to natural variation exacerbated by climate change and human activities. Yet, the interconnectedness between climate, caribou, and human well-being has received little attention. To address this gap, we bridged Indigenous and scientific knowledge in a single model, using as example the Porcupine caribou herd social-ecological system. Our analysis, involving 688 (fall season) and 616 (spring season) interviews conducted over nine years with 405 (fall season) and 390 (spring season) Indigenous hunters from nine communities, demonstrates that environmental conditions, large-scale temporal changes associated with caribou demography, and cultural practices affect hunters capacity to meet their needs in caribou. Our quantitative approach bolsters our understanding of the complex relationships between ecosystems and human welfare in environments exposed to rapid climate change, and shows the benefits of long-term participatory research methods implemented by Indigenous and scientific partners.

systems biology↗

bioRxiv2022

Intratumoral mregDC and CXCL13 T helper niches enable local differentiation of CD8 T cells following PD-1 blockade

Here, we leveraged a large neoadjuvant PD-1 blockade trial in patients with hepatocellular carcinoma (HCC) to search for correlates of response to immune checkpoint blockade (ICB) within T cell-rich tumors. We show that ICB response correlated with the clonal expansion of intratumoral CXCL13+ CH25H+ IL-21+ PD-1+ CD4 T helper cells (CXCL13+ Th) and Granzyme K+ PD-1+ effector-like CD8 T cells, whereas terminally exhausted CD39hi TOXhi PD-1hi CD8 T cells dominated in non-responders. Strikingly, most T cell receptor (TCR) clones that expanded post-treatment were found in pre-treatment biopsies. Notably, PD-1+ TCF-1+ progenitor-like CD8 T cells were present in tumors of responders and non-responders and shared clones mainly with effector-like cells in responders or terminally differentiated cells in non-responders, suggesting that local CD8 T cell differentiation occurs upon ICB. We found that these progenitor CD8 T cells interact with CXCL13+ Th cells within cellular triads around dendritic cells enriched in maturation and regulatory molecules, or "mregDC". Receptor-ligand analysis revealed unique interactions within these triads that may promote the differentiation of progenitor CD8 T cells into effector-like cells upon ICB. These results suggest that discrete intratumoral niches that include mregDC and CXCL13+ Th cells control the differentiation of tumor-specific progenitor CD8 T cell clones in patients treated with ICB.

immunology↗