X-Meeting presentations

REVERSE ENGINEERING OF MEDULLOBLASTOMA REGULATORY NETWORK AND INFERENCE OF MASTER REGULONS

Published in 21/11/2024 - ISBN: 978-65-272-0843-3

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Paper Title
REVERSE ENGINEERING OF MEDULLOBLASTOMA REGULATORY NETWORK AND INFERENCE OF MASTER REGULONS
Authors
  • Gustavo Lovatto Michaelsen
  • Tayrone de Sousa Monteiro
  • Danilo Oliveira Imparato
  • João Vitor Almeida da Costa
  • Daniel Rocha Silva
  • Iara Dantas de Souza
  • Marialva Sinigaglia
  • Rodrigo Juliani Siqueira Dalmolin
Modality
Poster
Subject area
Systems Biology and Modeling
Publishing Date
21/11/2024
Country of Publishing
Brazil | Brasil
Language of Publishing
Inglês
Paper Page
https://www.even3.com.br/anais/xmeeting-2024/833499-reverse-engineering-of-medulloblastoma-regulatory-network-and-inference-of-master-regulons
ISBN
978-65-272-0843-3
Keywords
medulloblastoma, transcription factor, systems biology, regulome
Summary
Medulloblastoma (MB) is the most common malignant pediatric brain tumor, accounting for approximately 20% of all childhood brain tumors. While recent advances have improved survival rates, current treatments like surgery, radiation, and chemotherapy lead to severe side effects and high morbidity, with around 30% of patients not achieving long-term survival. It is classified into four main molecular subgroups - WNT, SHH, Group 3, and Group 4 - each with distinct molecular characteristics and clinical features. The WNT and SHH subgroups are driven by mutations activating their respective signaling pathways. However, the highly aggressive Group 3 and Group 4 subgroups lack well-defined tumor drivers, hindering the development of targeted therapies. Identifying key transcriptional regulators, known as master regulators (MRs), can elucidate the dysregulated pathways underlying MB progression and uncover potential treatment targets. In this study, utilizing a dataset with 763 gene expression samples of primary MB, we inferred the MB regulatory network. Afterward, we applied the Master Regulator Analysis (MRA) identifying the transcription factors BHLHE41, RFX4, and NPAS3 among the most important regulators in the development of SHH, Group 3 and Group 4 MB subgroups. We also integrated the regulatory network with patient survival data. This analysis revealed eight MRs highly associated with patients' outcome, four regulators (MYC, REL, ZSCAN5A, and ZFAT) with activities associated with poor prognosis, and the remaining four (PAX6, ARNT2, ZNF157, and HIVEP3) acting antagonistically, being associated with good outcome. Our results offer key insights into the molecular mechanisms driving these tumors and identify novel potential therapeutic targets, addressing the urgent need for more effective and less toxic treatments.
Title of the Event
20º Congresso Brasileiro de Bioinformática: X-Meeting 2024
City of the Event
Salvador
Title of the Proceedings of the event
X-Meeting presentations
Name of the Publisher
Even3
Means of Dissemination
Meio Digital

How to cite

MICHAELSEN, Gustavo Lovatto et al.. REVERSE ENGINEERING OF MEDULLOBLASTOMA REGULATORY NETWORK AND INFERENCE OF MASTER REGULONS.. In: X-Meeting presentations. Anais...Salvador(BA) Hotel Deville Prime, 2024. Available in: https//www.even3.com.br/anais/xmeeting-2024/833499-REVERSE-ENGINEERING-OF-MEDULLOBLASTOMA-REGULATORY-NETWORK-AND-INFERENCE-OF-MASTER-REGULONS. Access in: 18/06/2025

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