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Autores principales: Ramos, Rodrigo Henrique, Bardelotte, Yago Augusto, Ferreira, Cynthia de Oliveira Lage, Simao, Adenilso
Formato: Preprint
Publicado: 2024
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Acceso en línea:https://arxiv.org/abs/2409.19115
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author Ramos, Rodrigo Henrique
Bardelotte, Yago Augusto
Ferreira, Cynthia de Oliveira Lage
Simao, Adenilso
author_facet Ramos, Rodrigo Henrique
Bardelotte, Yago Augusto
Ferreira, Cynthia de Oliveira Lage
Simao, Adenilso
contents Identifying driver genes is crucial for understanding oncogenesis and developing targeted cancer therapies. Driver discovery methods using protein or pathway networks rely on traditional network science measures, focusing on nodes, edges, or community metrics. These methods can overlook the high-dimensional interactions that cancer genes have within cancer networks. This study presents a novel method using Persistent Homology to analyze the role of driver genes in higher-order structures within Cancer Consensus Networks derived from main cellular pathways. We integrate mutation data from six cancer types and three biological functions: DNA Repair, Chromatin Organization, and Programmed Cell Death. We systematically evaluated the impact of gene removal on topological voids ($β_2$ structures) within the Cancer Consensus Networks. Our results reveal that only known driver genes and cancer-associated genes influence these structures, while passenger genes do not. Although centrality measures alone proved insufficient to fully characterize impact genes, combining higher-order topological analysis with traditional network metrics can improve the precision of distinguishing between drivers and passengers. This work shows that cancer genes play an important role in higher-order structures, going beyond pairwise measures, and provides an approach to distinguish drivers and cancer-associated genes from passenger genes.
format Preprint
id arxiv_https___arxiv_org_abs_2409_19115
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Identifying Key Genes in Cancer Networks Using Persistent Homology
Ramos, Rodrigo Henrique
Bardelotte, Yago Augusto
Ferreira, Cynthia de Oliveira Lage
Simao, Adenilso
Molecular Networks
Other Computer Science
Identifying driver genes is crucial for understanding oncogenesis and developing targeted cancer therapies. Driver discovery methods using protein or pathway networks rely on traditional network science measures, focusing on nodes, edges, or community metrics. These methods can overlook the high-dimensional interactions that cancer genes have within cancer networks. This study presents a novel method using Persistent Homology to analyze the role of driver genes in higher-order structures within Cancer Consensus Networks derived from main cellular pathways. We integrate mutation data from six cancer types and three biological functions: DNA Repair, Chromatin Organization, and Programmed Cell Death. We systematically evaluated the impact of gene removal on topological voids ($β_2$ structures) within the Cancer Consensus Networks. Our results reveal that only known driver genes and cancer-associated genes influence these structures, while passenger genes do not. Although centrality measures alone proved insufficient to fully characterize impact genes, combining higher-order topological analysis with traditional network metrics can improve the precision of distinguishing between drivers and passengers. This work shows that cancer genes play an important role in higher-order structures, going beyond pairwise measures, and provides an approach to distinguish drivers and cancer-associated genes from passenger genes.
title Identifying Key Genes in Cancer Networks Using Persistent Homology
topic Molecular Networks
Other Computer Science
url https://arxiv.org/abs/2409.19115