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Project JAGUAR: Discovering the Hidden Diversity of Immune Cells in Latin America

Evelia Lorena Coss-Navarrete 1, Diego Ramírez-Espinosa 1, Ana Laura Hernandez-Ledesma 1, Alejandra Schäfer 1, Grecia Sevilla-Parra 1, Marcela Sjoberg 2, Carolina Alvarez 2, Felipe Gajardo 2, Benilton de Sá Carvalho 3, Heitor de Paula Neto 4, Andreza Gama 4, Luis Tataje-Lavanda 5, Damaris Esquen-Bayona 5, Maximiliano Berro 6, Marina Fernandez 7, Pablo Romagnoli 7, Danilo Ceshin 7, Yesid Cuesta-Astroz 8, Carlos Camero 8, Julieth López-Castiblanco 8, Adriana Rojas 9, Liliana López Kleine 10, Tarran Rupall 11, Thais de Oliveira 11, Matiss Ozols 11, Anna Lorenc 11, Carla Jones 11, Gosia Trynka* 11, Alejandra Medina-Rivera* 1.

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1: Laboratorio Internacional de Investigación sobre el Genoma Humano (LIIGH-UNAM); 2: Facultad de Ciencias Biológicas de la Pontificia Universidad Católica de Chile (PUC), Chile; 3: Universidade Estadual de Campinas, Brazil; 4: Faculdade de Farmácia da Universidade Federal do Rio de Janeiro (UFRJ), Brazil; 5: Facultad de Ciencias de la Salud - EPMH. Universidad Privada San Juan Bautista (UPSJB), Peru; 6: Hospital de Clínicas de la Facultad de Medicina, Universidad de la República, Uruguay; 7: Centro de investigaciones en Medicina Traslacional ¨Severo R. Amuchástegui” (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Argentina; 8: Instituto Colombiano de Medicina Tropical, Colombia; 9: Pontificia Universidad Javeriana - Bogotá, Colombia; 10: Universidad Nacional de Colombia en Bogotá, Colombia; 11: Wellcome Sanger Institute, UK.

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Latin American populations (LATAM) result from genetic and cultural admixture among Indigenous, European, African and Asian groups, additionally shaped by the rich diversity of ecosystems and population migrations.

LATAM populations are underrepresented in genomic studies. Diminishing the benefit of these studies in our populations.

STUDY DESIGN:

MOTIVATION:

1080 volunteers

Figure 2. Methodological approach. Volunteers from seven Latin American countries will provide blood samples for PBMC isolation and analysis. Using single-cell technologies (scATAC-seq, scRNA-seq, CITE-seq, and whole genome sequencing), the study aims to explore how ancestry influences gene expression and immune cell composition. Data on health, lifestyle, and environment will also be collected. Whole Genome Sequencing (WGS), T-Cell Receptor (TCR) and B-Cell Receptor (BCR). PBMC: Peripheral blood mononuclear cells.

Volunteers recruitment

Recruitment progress

• Healthy volunteers from 7 Latin American countries
• Being native born in the country of collection
• Having parents born in the country of collection and preferentially also grandparents
• No chronic diseases
• No pregnancy
• 18-50 years old
• Signed informed consent INB, UNAM ethics Committee 093.H

50 % gender representation

This project was supported by the Chan-Zuckerberg Initiative (CZI). We thank LAVIS members Luis Aguilar, Alejandro León, and Jair García, and LIIGH members Carina Uribe Díaz, Alejandra Castillo Carbajal, and Christian Molina Aguilar for their support. Evelia Coss is postdoctoral from CONAHCYT (CVU 781634).

I sincerely appreciate Mauricio Guzmán, Paty Rodil Garcia, and Andy Bermeo de Jesus for their invaluable help on social media. My heartfelt gratitude goes to Mariana Villegas, Nadia Estrada, Sofia Hernandez, and Francisco Ramirez for their dedication in sampling and blood collection. We also thank the Blood Bank of Querétaro and AUNA ideas, especially Dr. Said González, Dr. Mercedes, Joseph Pinto and Ina Pérez, for their unwavering support.

Finally, I am deeply grateful to RIABIO, ISCB, and the JAGUAR project for their financial assistance, which made it possible for me to attend the conference and present this poster.

• We are actively recruiting participants in Chile, Argentina, Peru and Uruguay.
• We are generating high quality data to improve representation of Latin American diversity.
• Cell enrichment leads to higher cell type mapping resolution.
• Our project potentializes functional genomic studies in the Latin American population.
• Community engagement has strengthened our project, having a more significant social impact through science communication.

Anna Lorenc  (UK), Evelia Coss (Mexico), Diego Ramirez  (Mexico), Alejandra Schäfer (Mexico), Alejandra Medina (Mexico), Thais de Oliveira  (Brazil), Benilton de Sá Carvalho (Brazil), Julieth López (Colombia), Tarran Rupall (UK), Bess Chau (UK), Felipe Gajardo (Chile), Yesid Cuesta (Colombia), Liliana Lopez Kleine (Colombia), Gosia Trynka (UK), Danilo Ceshin (Argentina) and Marina Fernandez (Argentina).

Ana Laura Hernández-Ledesma (Mexico), Pablo Alberto Romagnoli (Argentina), Marina Fernandez (Argentina), Marcela Sjöberg (Chile) and Carla Jones (UK)

Bioinformatic team

Immunology experts

Ana Laura Hernández-Ledesma (Mexico), Alejandra Schäfer (Mexico), Grecia Sevilla (Mexico), Evelia Coss (Mexico), Marina Fernandez (Argentina), Carlos Camero (Colombia), Carla Jones (UK), Melanie Ccaico (Peru), Edith Málaga (Peru), Fabrizio Vásquez (Peru).

Participant recruitment and sample preparation team

Figure 1. Donor diversity in different functional genomics datasets and resources. (A and B) Genetic ancestry is displayed for a set of commonly used cancer cell lines, the eQTL Catalog, and TCGA in (A), while (B) shows self-identified ethnicity across various epigenome-wide association studies (EWASs). TCGA: The Cancer Genome Atlas Program; eQTL: Expression Quantitative trait loci. Figure adapted from George S, et al. 2023. CellPress. DOI: https://doi.org/10.1016/j.ajhg.2023.10.012

Table. Sampling Status and Country Information. IRB: Institutional Review Board

Nov 1st 2024

AIM 1: To deeply characterize the immune cell composition across the LATAM populations.

AIM 2: To characterize regulatory networks and mechanisms influenced by genetic variation across LATAM populations.

AIM 3: To build at LATAM PBMC biobank for future studies such as those linking genetic variants to changes in gene expression.

Integration of Regulatory Networks

Population specific regulatory interactions

Regulatory effects of genetic variation

Ancestry Networks for the Human Cell Atlas

Co-principal investigators

Figure 3. Sex and Age Distribution in the JAGUAR Project. (A) Distribution of sex and age by country. (B) Percentage distribution of sexes by country. (C) Boxplot showing the dispersion of males and females across countries.

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Cell enrichment leads to higher mapping resolution

regional coverage of the obtained samples across countries

Diego Ramírez-Espinosa

Single cell approaches to large-scale multiomic analysis in the framework of JAGUAR Project

Mexico

scATAC-seq, multiomic, regulatory networks

Felipe Gajardo

CITER: A Cluster-Focused Approach for Cell-Type Annotation and Hierarchy Inference in Multimodal Data

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Chile

scCITE-seq, Annotation, Machine learning

Julieth López-Castiblanco

Comparison of differential expression methods in single cell RNA sequencing data

Colombia

scRNA-seq, Differential expression, metacells

Monocytes and Dendritic Cells

T-cells

Natural Killer cells