Strengthening collaborative research in pediatric tumor diagnostics through integrated transcriptome and methylation analyses

• Grant number: 25/12900-3
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: October 31, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Mariana Tomazini Pinto
• Grantee: Mariana Tomazini Pinto
• Principal researcher abroad: Jeremy Wang
• Institution abroad: University of North Carolina at Chapel Hill (UNC), United States
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP)
• Associated research grant: 19/07502-8 - Investigation of the transcription factors inducing Epithelial-Mesenchymal Transition (EMT) in germ cells tumors, AP.JP

Abstract

This proposal aims to strengthen the ongoing collaboration between the Pediatric Oncology Research Group led by Dr. Mariana Tomazini at Barretos Cancer Hospital, Brazil, and the Wang Lab, led by Dr. Jeremy Wang at the University of North Carolina at Chapel Hill (UNC), USA. This partnership started from the shared interest in advancing molecular diagnostics of pediatric tumors using state-of-the-art methodologies such as Oxford Nanopore Technologies and Illumina, Inc.The Wang Lab has been using this method to explore genomic, transcriptomic, and epigenomic alterations in pediatric tumors with machine learning approaches that can become a diagnostic tool, especially in low-resource settings. The Pediatric Oncology Research Group focuses on Germ Cell Tumors (GCT) and more recently on Leukemias, and this partnership is vital to keep expanding this work. Our collaboration includes exploring the transcriptional profile of GCTs and leukemias and its use to distinguish histological and molecular subtypes through a machine learning classifier developed at UNC. Therefore, the proposal has the following goals: 1. To develop and validate classifiers for pediatric tumor subtypes using long-read transcriptome and methylation data; 2. To implement adaptive sampling techniques to enhance coverage of specific genomic and epigenomic regions in tumor tissues; 3. To compare molecular signatures across Brazilian and U.S. tumor cohorts for validation; 4. To publicly release optimized protocols and bioinformatics pipelines to support reproducibility. The strengthening of this partnership will allow this study to go further and keep the ongoing transcriptomic work and start exploring the methylation profile of these tumors, as well as apply new tools of enrichment or depletion of targets while sequencing. (AU)