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Systems Biology Approaches Reveal Potential Phenotype-Modifier Genes in Neurofibromatosis Type 1

Neurofibromatosis type (NF1) is a syndrome characterized by varied symptoms, ranging from mild to more aggressive phenotypes. The variation is not explained only by genetic and epigenetic changes in the NF1 gene and the concept of phenotype-modifier genes in extensively discussed in an attempt to ex...

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Autores principales: Woycinck Kowalski, Thayne, Brussa Reis, Larissa, Finger Andreis, Tiago, Ashton-Prolla, Patricia, Rosset, Clévia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565824/
https://www.ncbi.nlm.nih.gov/pubmed/32858845
http://dx.doi.org/10.3390/cancers12092416
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author Woycinck Kowalski, Thayne
Brussa Reis, Larissa
Finger Andreis, Tiago
Ashton-Prolla, Patricia
Rosset, Clévia
author_facet Woycinck Kowalski, Thayne
Brussa Reis, Larissa
Finger Andreis, Tiago
Ashton-Prolla, Patricia
Rosset, Clévia
author_sort Woycinck Kowalski, Thayne
collection PubMed
description Neurofibromatosis type (NF1) is a syndrome characterized by varied symptoms, ranging from mild to more aggressive phenotypes. The variation is not explained only by genetic and epigenetic changes in the NF1 gene and the concept of phenotype-modifier genes in extensively discussed in an attempt to explain this variability. Many datasets and tools are already available to explore the relationship between genetic variation and disease, including systems biology and expression data. To suggest potential NF1 modifier genes, we selected proteins related to NF1 phenotype and NF1 gene ontologies. Protein–protein interaction (PPI) networks were assembled, and network statistics were obtained by using forward and reverse genetics strategies. We also evaluated the heterogeneous networks comprising the phenotype ontologies selected, gene expression data, and the PPI network. Finally, the hypothesized phenotype-modifier genes were verified by a random-walk mathematical model. The network statistics analyses combined with the forward and reverse genetics strategies, and the assembly of heterogeneous networks, resulted in ten potential phenotype-modifier genes: AKT1, BRAF, EGFR, LIMK1, PAK1, PTEN, RAF1, SDC2, SMARCA4, and VCP. Mathematical models using the random-walk approach suggested SDC2 and VCP as the main candidate genes for phenotype-modifiers.
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spelling pubmed-75658242020-10-26 Systems Biology Approaches Reveal Potential Phenotype-Modifier Genes in Neurofibromatosis Type 1 Woycinck Kowalski, Thayne Brussa Reis, Larissa Finger Andreis, Tiago Ashton-Prolla, Patricia Rosset, Clévia Cancers (Basel) Article Neurofibromatosis type (NF1) is a syndrome characterized by varied symptoms, ranging from mild to more aggressive phenotypes. The variation is not explained only by genetic and epigenetic changes in the NF1 gene and the concept of phenotype-modifier genes in extensively discussed in an attempt to explain this variability. Many datasets and tools are already available to explore the relationship between genetic variation and disease, including systems biology and expression data. To suggest potential NF1 modifier genes, we selected proteins related to NF1 phenotype and NF1 gene ontologies. Protein–protein interaction (PPI) networks were assembled, and network statistics were obtained by using forward and reverse genetics strategies. We also evaluated the heterogeneous networks comprising the phenotype ontologies selected, gene expression data, and the PPI network. Finally, the hypothesized phenotype-modifier genes were verified by a random-walk mathematical model. The network statistics analyses combined with the forward and reverse genetics strategies, and the assembly of heterogeneous networks, resulted in ten potential phenotype-modifier genes: AKT1, BRAF, EGFR, LIMK1, PAK1, PTEN, RAF1, SDC2, SMARCA4, and VCP. Mathematical models using the random-walk approach suggested SDC2 and VCP as the main candidate genes for phenotype-modifiers. MDPI 2020-08-26 /pmc/articles/PMC7565824/ /pubmed/32858845 http://dx.doi.org/10.3390/cancers12092416 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Woycinck Kowalski, Thayne
Brussa Reis, Larissa
Finger Andreis, Tiago
Ashton-Prolla, Patricia
Rosset, Clévia
Systems Biology Approaches Reveal Potential Phenotype-Modifier Genes in Neurofibromatosis Type 1
title Systems Biology Approaches Reveal Potential Phenotype-Modifier Genes in Neurofibromatosis Type 1
title_full Systems Biology Approaches Reveal Potential Phenotype-Modifier Genes in Neurofibromatosis Type 1
title_fullStr Systems Biology Approaches Reveal Potential Phenotype-Modifier Genes in Neurofibromatosis Type 1
title_full_unstemmed Systems Biology Approaches Reveal Potential Phenotype-Modifier Genes in Neurofibromatosis Type 1
title_short Systems Biology Approaches Reveal Potential Phenotype-Modifier Genes in Neurofibromatosis Type 1
title_sort systems biology approaches reveal potential phenotype-modifier genes in neurofibromatosis type 1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565824/
https://www.ncbi.nlm.nih.gov/pubmed/32858845
http://dx.doi.org/10.3390/cancers12092416
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