Dataset Information

A Novel Approach for Identifying Relevant Genes for Breast Cancer Survivability on Specific Therapies.

ABSTRACT: Analyzing the genetic activity of breast cancer survival for a specific type of therapy provides a better understanding of the body response to the treatment and helps select the best course of action and while leading to the design of drugs based on gene activity. In this work, we use supervised and nonsupervised machine learning methods to deal with a multiclass classification problem in which we label the samples based on the combination of the 5-year survivability and treatment; we focus on hormone therapy, radiotherapy, and surgery. The proposed nonsupervised hierarchical models are created to find the highest separability between combinations of the classes. The supervised model consists of a combination of feature selection techniques and efficient classifiers used to find a potential set of biomarker genes specific to response to therapy. The results show that different models achieve different performance scores with accuracies ranging from 80.9% to 100%. We have investigated the roles of many biomarkers through the literature and found that some of the discriminative genes in the computational model such as ZC3H11A, VAX2, MAF1, and ZFP91 are related to breast cancer and other types of cancer.

SUBMITTER: Tabl AA

PROVIDER: S-EPMC6088467 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A Novel Approach for Identifying Relevant Genes for Breast Cancer Survivability on Specific Therapies.

Tabl Ashraf Abou AA Alkhateeb Abedalrhman A Pham Huy Quang HQ Rueda Luis L ElMaraghy Waguih W Ngom Alioune A

Evolutionary bioinformatics online 20180810

Analyzing the genetic activity of breast cancer survival for a specific type of therapy provides a better understanding of the body response to the treatment and helps select the best course of action and while leading to the design of drugs based on gene activity. In this work, we use supervised and nonsupervised machine learning methods to deal with a multiclass classification problem in which we label the samples based on the combination of the 5-year survivability and treatment; we focus on ...[more]

PMID: 30116102

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Project description:Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA), a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive) and thymine degradation pathways (p = 1.06-08) were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis). The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67). In conclusion, gene network analysis identified novel molecules and biological processes, including pathways related to inflammation and oxidative stress, that are relevant to mucositis development, thus providing the basis for future studies to improve the management and treatment of mucositis in patients with cancer.

Dataset Information

A Novel Approach for Identifying Relevant Genes for Breast Cancer Survivability on Specific Therapies.

Publications

A Novel Approach for Identifying Relevant Genes for Breast Cancer Survivability on Specific Therapies.

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