Predicting environmental chemical factors associated with disease-related gene expression data

Patel, Chirag; Butte, Atul J.

doi:10.1186/1755-8794-3-17

Cited by 24 publications

(34 citation statements)

References 71 publications

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“…We reasoned that if environmental chemical dysregulated genes were also found to be coordinately dysregulated in breast cancer, then the environmental chemical could be etiologically associated with breast cancer. A similar approach has been used previously with gene expression data to predict environmental chemicals associated with disease (Patel and Butte 2010). …”

Section: Methodsmentioning

confidence: 99%

Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development

Gopalakrishnan

Teitelbaum

Lambertini

et al. 2017

Environmental Research

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Exposure to environmental chemicals has been linked to altered mammary development and cancer risk at high doses using animal models. Effects at low doses comparable to human exposure remain poorly understood, especially during critical developmental windows. We investigated the effects of two environmental phenols commonly used in personal care products – methyl paraben (MPB) and triclosan (TCS) – on the histology and transcriptome of normal mammary glands at low doses mimicking human exposure during critical windows of development. Sprague-Dawley rats were exposed during perinatal, prepubertal and pubertal windows, as well as from birth to lactation. Low-dose exposure to MPB and TCS induced measurable changes in both mammary histology (by Masson’s Trichrome Stain) and transcriptome (by microarrays) in a window-specific fashion. Puberty represented a window of heightened sensitivity to MPB, with increased glandular tissue and changes of expression in 295 genes with significant enrichment in functions such as DNA replication and cell cycle regulation. Long-term exposure to TCS from birth to lactation was associated with increased adipose and reduced glandular and secretory tissue, with expression alterations in 993 genes enriched in pathways such as cholesterol synthesis and adipogenesis. Finally, enrichment analyses revealed that genes modified by MPB and TCS were over-represented in human breast cancer gene signatures, suggesting possible links with breast carcinogenesis. These findings highlight the issues of critical windows of susceptibility that may confer heightened sensitivity to environmental insults and implicate the potential health effects of these ubiquitous environmental chemicals in breast cancer.

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Section: Methodsmentioning

confidence: 99%

Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development

Gopalakrishnan

Teitelbaum

Lambertini

et al. 2017

Environmental Research

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“…In fact, these tools are already being integrated to derive hypotheses between genes, chemical exposures and disease [35]. However, given the large numbers of chemicals to be interrogated, and practical and cost limitations associated with whole transcriptome analysis, strategies to develop targeted gene panels are useful.…”

Section: Discussionmentioning

confidence: 99%

“…4 reports the extent of overlap between the genes identified as part of the Enrichr pathway and those in BC Screen. Using the Sporadic Breast Cancer pathway from GEO again, 35 BCScreen genes (9%) were represented in the 400 named as part of the Sporadic Breast Cancer Pathway in GEO. The two most significantly enriched pathways identified were the integrated pancreatic cancer pathway in WikiPathways, and the response to steroid hormones process in GO.…”

Section: Characteristicmentioning

confidence: 99%

BCScreen: A gene panel to test for breast carcinogenesis in chemical safety screening

Grashow

Rosa

Watford

et al. 2018

Computational Toxicology

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A B S T R A C TTargeted gene lists have been used in clinical settings to specify breast tumor type, and to predict breast cancer prognosis and response to treatment. Separately, panels have been curated to predict systemic toxicity and xenoestrogen activity as a part of chemical screening strategies. However, currently available panels do not specifically target biological processes relevant to breast development and carcinogenesis. We have developed a gene panel called the Breast Carcinogen Screen (BCScreen) as a tool to identify potential breast carcinogens and characterize mechanisms of toxicity. First, we used four seminal reviews to identify 14 key characteristics of breast carcinogenesis, such as apoptosis, immunomodulation, and genotoxicity. Then, using a hybrid data and knowledge-driven framework, we systematically combined information from whole transcriptome data from genomic databases, biomedical literature, the CTD chemical-gene interaction database, and primary literature review to generate a panel of 500 genes relevant to breast carcinogenesis. We used normalized pointwise mutual information (NPMI) to rank genes that frequently co-occurred with key characteristics in biomedical literature. We found that many genes identified for BCScreen were not included in prognostic breast cancer or systemic toxicity panels. For example, more than half of BCScreen genes were not included in the Tox21 S1500+ general toxicity gene list. Of the 230 that did overlap between the two panels, representation varied across characteristics of carcinogenesis ranging from 21% for genes associated with epigenetics to 82% for genes associated with xenobiotic metabolism. Enrichment analysis of BCScreen identified pathways and processes including response to steroid hormones, cancer, cell cycle, apoptosis, DNA damage and breast cancer. The biologically-based systematic approach to gene prioritization demonstrated here provides a flexible framework for creating diseasefocused gene panels to support discovery related to etiology. With validation, BCScreen may also be useful for toxicological screening relevant to breast carcinogenesis.

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“…In the health care area, social network analysis helps researchers to understand each disease and human gene relationships based on overall disease-gene network structures [11,12]. This aspect is important because it helps us to understand network structures of diseases and related associational human gene and identify the characteristics of the most influential human gene in the early phase of a disease.…”

Section: Social Network Analysis Social Network Analysis (Sna)mentioning

confidence: 99%

The Information Filtering of Gene Network for Chronic Diseases: Social Network Perspective

Choi

Kwon

2015

International Journal of Distributed Sensor Networks

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Web and mobile platforms have provided an environment of technical cooperation through technical development and the diffusion of related devices. Large-scale data sets have been available to analyze web interaction and data analysis. Particularly, large-scale data make us learn new patterns and insight into several research fields. For healthcare field, most chronic diseases are caused by environmental and genetic factors (Van der Laan et al., 2003). The relationship between environmental exposure and gene factors is crucial regarding disease etiology (Swift et al., 2004). For example, Tobacco is considered one of the biggest environmental factors responsible for many diseases each year. Schwartz and Collins (2007) discussed the importance of gene and environment factor correlation in human diseases. Thomas (2010) published a review of different approaches on gene-environment association studies attempting to explain some of the most complex diseases. Although previous studies have studied chronicle diseases with their causes one by one, those studies do not show integrated relationships between various diseases and their related human genes. Therefore, this study investigates the gene-disease relationships which are affected by tobacco and is able to find new association links with social network analysis and other mining techniques.

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Predicting environmental chemical factors associated with disease-related gene expression data

Cited by 24 publications

References 71 publications

Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development

Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development

BCScreen: A gene panel to test for breast carcinogenesis in chemical safety screening

The Information Filtering of Gene Network for Chronic Diseases: Social Network Perspective

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