CERC team members at IGES and ASHG conferences in Denver !

Last week was a big week, full of accomplishments, for 9 CERC team members who accompanied Vincent Mooser, CERC Chairholder, to the American Society of Human Genetics (ASHG) annual meeting on Nov 5-9, 2024 in Denver Colorado. One of them also attended the International Genetic Epidemiology Society (IGES) annual meeting on Nov 3-4, 2024, just before ASHG conference.

3 MSc students, 2 PhD students, 2 bioinformaticians and 1 post-doc got their abstract selected for posters presentation. You can find their abstract below:

• MSc students: Alyssa Green, Juliano Malizia, Irene Pender

• PhD students: Peyton McClelland, Thomas Zheng

• Bioinformaticians: Vincent Chapdelaine, Justin Pelletier

• Post-doc: Benoît Delabays

Finally we must congratulate Chen-Yang Su for not one but two big achievements ! His abstracts won 2 awards in each conference ! At IGES, Chen-Yang received the Roger Williams Award Finalist which rewards the top 4 abstracts by a student enrolled in a bachelor, master or PhD program at the IGES Annual Meeting among hundreds of abstract submissions. At ASHG, Chen-Yang was invited to give a talk at the Platform Oral Presentation rewarding the top 10% of abstracts submitted to the conference. Please find his abstracts below:

• IGES

• ASHG

CERC EDI strategy revised

The CERC EDI-in-Action Committee is proud to present the 2nd version of the CERC EDI strategy. The initial CERC EDI strategy outlined five commitments and specific actions. In 2023, the CERC team submitted a 2-page summary of progress on EDI activities for the Tri-agency Institutional Programs Secretariat (TIPS) mid-term report. In 2024, applying TIPS’ mid-term review recommendations, the CERC-EAC decided to revised its EDI Strategy, and associated EDI Workplan/Roadmap until the end of the CERC Program.

The main changes are the following: producing a CERC annual EDI survey, organizing a retreat on EDI in CERC projects related to underrepresented groups, updating the student recruitment processes to improve the representation of Canadian diversity, as well as implementing a targeted recruitment strategy corresponding to various projects' needs. The Program’s EDI Strategy is fundamental and transversal, cutting across the scientific, governance, recruitment, and training facets of the Program. This Strategy is defined by five principal commitments, described below:  

EDI commitments:

1. Ensuring that research projects within the CERC Program include and benefit diverse social groups

2. Equitable representation across ranks/groups among faculty and trainees working in connection with the Program

3. Building an inclusive and respectful climate

4. Developing and implementing an effective mode of receiving disclosures of EDI-related conflicts or challenges

5. Transparency in commitments, metrics, progress, and outcomes

Visit of Ignazio Cassis, Swiss Minister of Foreign Affairs, at McGill University

Mr Ignazio Cassis, Swiss Minister of Foreign Affairs, and a delegation including 3 Ambassadors and 3 Consuls, visited McGill on October 30th, 2024, for a lunch at the Faculty Club. The goal of the meeting was to give to this delegation an overview of McGill and a description of the multi-disciplinary approach that McGill is using to develop and implement genomic medicine. Vincent Mooser, CERC Chairholder, was leading the McGill delegation, including Dominique Bérubé, Vice-Principal (Research and Innovation) and Anja Geitmann, Vice-Principal (Global Engagement). It became immediately apparent during the meeting that genomic medicine is a perfect topic for Diplomacy and Science, an area of high interest for the Swiss Department of Foreign Affairs.

Chen-Yang Su awarded the Best Oral Presentation CMDO Annual Symposium on Health Research and Artificial Intelligence

We would like to congratulate Chen-Yang Su, PhD student of the McGill CERC in Genomic Medicine, who was awarded the Best Oral Presentation at the Cardiometabolic Health, Diabetes and Obesity Research Network (CMDO) Annual Symposium on Health Research and Artificial Intelligence on October 24th, 2024.

You will find the abstract of his presentation below:

Multi-ancestry proteome-phenome-wide Mendelian randomization offers a comprehensive protein-disease atlas and potential therapeutic targets  

Authors 
Su Chen-Yang, MSc *[1,2], van der Graaf Adriaan, PhD [3], Zhang Wenmin, PhD [4], Selber-Hnatiw, Susannah, MSc [2,5], Richards Brent, MD, MSc [5,6,7,8,9], Flannick Jason, PhD [10,11], Zhou Sirui, PhD [2,5], Mooser Vincent, MD [2,5], Lu Tianyuan, PhD [12,13,14,15], Yoshiji Satoshi, MD, PhD [2,5,6,10,11]

Objective: Circulating proteins influence disease risk and are valuable drug targets. To increase the discovery of protein-phenotype associations and identify therapeutic targets for diverse populations, we conducted multi-ancestry proteome-phenome-wide Mendelian randomization (MR), followed by sensitivity analyses and druggability assessment.

Methods: We performed two-sample MR, analyzing 2,265 unique proteins from two platforms (SomaScan v4 and Olink Explore 3072)—2,110 proteins from four European cohorts (n = up to 35,559 individuals), 1,144 from two African cohorts (n = up to 1,871), and 581 from a novel East Asian cohort (n = 1,823). We curated the largest GWAS for 179 traits in Europeans, 26 in Africans, and 206 in East Asians. To reduce horizontal pleiotropy, we ensured instruments were cis-pQTL for the protein of interest and had the highest Open Targets variant-to-gene score. We performed sensitivity analyses including colocalization with PwCoCo and SharePro, a novel method we recently developed. We evaluated shared causal effects of prioritized proteins across ancestries and assessed overlap with the druggable genome, Open Targets, and DrugBank.

Results: We tested 726,035 protein-phenotype pairs in Europeans, 33,078 in Africans, and 115,352 in East Asians. Notably, 119 proteins were instrumentable only in Africans and 17 proteins only in East Asians due to allele frequency differences that are common in these ancestries but rare in Europeans.  We identified 3,949, 56, and 325 unique protein-phenotype pairs in European, African, and East Asian populations, respectively. To showcase our findings, we illustrated the causal role of IL1RL1 in inflammatory bowel diseases, which was supported by multiple lines of evidence.

Conclusion: This study provides the largest multi-ancestry atlas of protein-disease associations, expanding insights into disease etiology and opportunities for prioritizing therapeutic targets. Results are available at the Common Metabolic Diseases Knowledge Portal (https://hugeamp.org/r/protein_mr_atlas).

2024 CERC/C150 Symposium

From October 21 to 23, 2024, Vincent Mooser and Claire Le Moigne attended the 2024 CERC/C150 Symposium hosted by the University of Sherbrooke. This is the 2nd edition of a symposium which was first organized by McGill in June 2021. This event was made possible through a collaboration between the Tri-agency Institutional Programs Secretariat (TIPS) and the UdeS. This conference was gathering CERC and C150 chairholders, CERC team members and employees involved in CERC/C150 application, management and reporting from many Universities in Canada.

Other colleagues from McGill committed with the CERC in Genomic Medicine were also attending the conference:

• Kristina Öhrvall, Assistant Vice-President, Research Development: CERC Oversight Committee and CERC EDI-in-Action committee member

• Magdalena Maslowska, Senior Advisor, Research Development (Biomedical and Health Sciences): CERC EDI-in-Action committee member.

Vincent Mooser chaired a Panel discussion on Preparing the Chairholder for the Canadian Research Environment with the following panelists:

• Sara Hart, Canadian Excellence Research Chair in Developmental Science, University of Waterloo

• Shinichi Nakagawa, Canada Excellence Research Chair in Open Science and Synthesis in Ecology and Evolution, University of Alberta

• Sriram Subramaniam, Canada Excellence Research Chair in Precision Cancer Drug Design, University of British Columbia

Kristina Öhrvall also shared the knowledge and good practices from McGill University during the Panel discussion titled Life Post CERC-C150 - Transitioning out of a CERC or C150.

Raquel Cuella Martin awarded a Gairdner Early Career Investigator Award

The CERC team is pleased to announce that Raquel Cuella Martin, one of its Assistant Professor, was among the five investigators selected by the Gairdner Foundation for a prestigious Early Career Investigator Award ! Cuella Martin will present her research on precision genome engineering ("Understanding unique protein features with precision genome engineering") alongside the 2024 Gairdner Awardees during the Laureate Lecture at the Gairdner Science Week 2024 events in Toronto from October 23 to 25. Learn more.

The CERC team welcomes a new Assistant Professor : Satoshi Yoshiji

The CERC team has the pleasure to welcome a new Assistant Professor in the team, Satoshi Yoshiji.

Satoshi Yoshiji (pronounced “yo-she-gee”) is an Assistant Professor with expertise in endocrinology, genetic epidemiology, and biostatistics. His research goal is to leverage genomics, proteomics, and other omics to identify therapeutic targets and advance precision medicine for diabetes, obesity, cardiovascular diseases, and beyond. After earning board certifications in Endocrinology and Internal Medicine in Japan, he obtained his PhD in Human Genetics at McGill University (Joint PhD with Kyoto University). He worked as a Research Fellow at the Broad Institute of MIT and Harvard before returning to McGill as a Principal Investigator. He serves as a co-PI for BioPortal, a new multi-ancestry, multi-omics biobank of 12,500 individuals in Montreal. He is recruiting ambitious, forward-looking students and staff.

If you want to know more about Satoshi Yoshiji, please consult his personal website here !

Human Genetics Research Day 2024

The CERC team wants to congrats Peyton McClelland for winning the 3-min presentation of the Human Genetics Research Day, organized by the Department of Human Genetics of McGill on May 30, 2024.

Over 150 students and faculty participated to this event, showing the dynamism of Genetics at McGill. Dr. Stephen Scherer for joined the participants as the keynote speaker under the Scriver Family Visiting Professorship in Genetic Medicine, with his talk entitled: “Every biological study will be enlightened by an accompanying genome sequence”.

Peyton presented a 3-min talk titled Investigating HLA in a Quebec population-based biobank about her work in the CERC team on analyzing and imputing HLA in the CARTaGENE biobank to enable cataloguing HLA variation and disease association in the Quebec population.

You will find the whole abstract of the presentation below:

Calling HLA allele variation in the Quebec population-based CARTaGENE cohort using whole-genome sequencing data.

Peyton McClelland, Ken Sin Lo, Guillaume Lettre, Claude Bhérer, Daniel Taliun

The human leukocyte antigen (HLA) system contains genes involved in many immunological processes, and HLA variation is associated with many disease-related phenotypes, including type I diabetes, multiple sclerosis, and rheumatoid arthritis. HLA allele frequencies differ significantly across populations, making population-specific HLA characterisation necessary to understand the HLA variation within a given population. We built a catalogue of high-resolution HLA alleles in the province of Quebec, using high-depth whole-genome sequencing (WGS) data from 2,180 participants from CARTaGENE, a population-based cohort with recruitment centers in six regions of Quebec that has collected high-quality biosamples and extensive health information. We performed HLA typing of class I and II classical alleles using the HLA*LA method. After quality checks, 44,634 alleles were retrieved from 2,088 participants. 307 individual HLA alleles were observed at least once in the CARTaGENE WGS dataset. Of these, 262 HLA alleles were also present in the most extensive publicly available multi-ancestry high-resolution HLA reference panel, HLA-TAPAS (n=21,546). 49 of 262 HLA alleles were at significantly different frequencies in the CARTaGENE cohort (p < 2.15 x 10-4). Frequencies of 51 low-resolution (one-field) HLA allele types were also previously reported in the Hema-Quebec donor biobank in 17 administrative regions of Quebec. We compared regional allele frequencies in CARTaGENE to the Hema-Quebec cohort. In the CARTaGENE WGS dataset, frequencies of 38 shared HLA alleles correlated well with province-wide frequencies in Hema-Quebec (Pearson’s r = 0.9841); 2 alleles were at significantly different frequencies in CARTaGENE (p < 1.32x 10-3). For individual CARTaGENE sampling regions, HLA allele frequencies were well correlated with corresponding Hema-Quebec regions, with Pearson’s r ranging from 0.88-0.93. These preliminary findings suggest that sequencing-based HLA calling in the Quebec population may yield population-specific differences in HLA variation and disease associations, for which specialized methods for population-specific imputation and analysis will be developed.

Fellowships award successes

It is with great pride that we congratulate the CERC members who have recently been awarded scholarships.

First of all, Claude Bhérer and Raquel Cuella Martin have both been awarded the Research Scholars - Junior 1 bursary funded by the Fonds de Recherche du Québec en Santé (FRQS). This scholarship will finance part of their salary for 4 years, as well as some research expenses.

The FRQS also awarded scholarships to 3 students: Alyssa Green, who received a Master's Training Scholarship for 2 years, as well as Susannah Selber-Hnatiw and Amisha Minju, who received a Doctoral Training Scholarship for 4 years.

Finally, 2 other students were also successful in winning Canadian Institutes of Health Research scholarships: Irene Pender was awarded the Canada Graduate Scholarships-Master's (CGS-M) while Juliano Malizia won the CIHR Strategic Master's Award - Computational Biology and Health Data Sciences, both for one year.

Congratulations to all our successful applicants!

Chen-Yang Su wins the Best poster presentation at the HBHL Symposium on May 8-9, 2024

Congratulations to Chen-Yang Su, PhD student of the McGill CERC in Genomic Medicine for winning the Best poster presentation at the Healthy Brains Healthy Lives (HBHL) Symposium on May 8-9, 2024 !

You will find the abstract of his presentation below:

Authors
Chen-Yang Su, Sirui Zhou

Proteomics and metabolomics integration uncovers molecular signatures associated with neuroprotective signatures in post-acute SARS-CoV-2 infection

Introduction: Post-acute sequelae SARS-CoV-2 (PASC) is an emerging public health concern with heterogeneous manifestations. Among PASC symptoms, long-term neurological manifestations are particularly debilitating. Their molecular underpinning remains poorly understood. Here, we combined proteomics and metabolomics to address this issue.

Methods: Proteomic and metabolomic data were generated for 1,234 individuals from the Biobanque Québécoise de la COVID-19 (BQC19), which followed COVID-19 patients over two years. After quality control, 4,984 proteins and 943 metabolites were retained for analysis. Using 689 clinical entries from the BQC19, we defined broad neurological PASC (BNP) as any neurological manifestations, whereas refined neurological PASC (RNP) was defined as neurological complications that either recently appeared or deteriorated due to COVID-19. We then fitted single biomarker logistic regression models while adjusting for age at diagnosis and sex to determine the association of each protein or metabolite with BNP or RNP.

Results: A total of 381 and 65 cases with both proteomics and metabolomics data met our definition of BNP and RNP and were compared with 535 and 713 controls, respectively. A total of 1,416 and 734 proteins were found significantly associated with BNP and RNP, respectively, with 544 overlapping proteins. In addition, 158 and 130 metabolites were found significantly associated with BNP and RNP, respectively, with 53 overlapping metabolites. In particular, we identified phosphatidylethanolamine-binding protein 1 (PEBP1) as being protective against BNP (OR (95% CI) = 0.76 (0.66-0.87), FDR p = 0.002) and RNP (OR (95% CI) = 0.61 (0.46-0.81), FDR p = 0.014). Interestingly enough, previous studies suggested downregulation of PEBP1 may lead to Alzheimer’s disease. Moreover, PEBP1 functions as an enzyme for 1-palmitoyl-2-docosahexaenoyl-GPE, a phosphatidylethanolamine (PE) whose impairment may lead to neurodegenerative disorders, which is concordant with our finding that increased circulating PE is associated with decreased neurological PASC risk (BNP: OR (95% CI) = 0.78 (0.68-0.90), FDR p = 0.01; RNP: OR (95% CI) = 0.56 (0.41-0.75), FDR p = 0.006).

Conclusion: Here, we used an integrative bi-omics approach combining proteomics and metabolomics to provide new insight into the pathophysiological mechanisms underlying neurological PASC risk which, possibly, could point to new ways to treat this condition.