Dataset Information

Toxicogenomics and cancer susceptibility: advances with next-generation sequencing.

ABSTRACT: The aim of this review is to comprehensively summarize the recent achievements in the field of toxicogenomics and cancer research regarding genetic-environmental interactions in carcinogenesis and detection of genetic aberrations in cancer genomes by next-generation sequencing technology. Cancer is primarily a genetic disease in which genetic factors and environmental stimuli interact to cause genetic and epigenetic aberrations in human cells. Mutations in the germline act as either high-penetrance alleles that strongly increase the risk of cancer development, or as low-penetrance alleles that mildly change an individual's susceptibility to cancer. Somatic mutations, resulting from either DNA damage induced by exposure to environmental mutagens or from spontaneous errors in DNA replication or repair are involved in the development or progression of the cancer. Induced or spontaneous changes in the epigenome may also drive carcinogenesis. Advances in next-generation sequencing technology provide us opportunities to accurately, economically, and rapidly identify genetic variants, somatic mutations, gene expression profiles, and epigenetic alterations with single-base resolution. Whole genome sequencing, whole exome sequencing, and RNA sequencing of paired cancer and adjacent normal tissue present a comprehensive picture of the cancer genome. These new findings should benefit public health by providing insights in understanding cancer biology, and in improving cancer diagnosis and therapy.

SUBMITTER: Ning B

PROVIDER: S-EPMC5712441 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Toxicogenomics and cancer susceptibility: advances with next-generation sequencing.

Ning Baitang B Su Zhenqiang Z Mei Nan N Hong Huixiao H Deng Helen H Shi Leming L Fuscoe James C JC Tolleson William H WH

Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews 20140101 2

The aim of this review is to comprehensively summarize the recent achievements in the field of toxicogenomics and cancer research regarding genetic-environmental interactions in carcinogenesis and detection of genetic aberrations in cancer genomes by next-generation sequencing technology. Cancer is primarily a genetic disease in which genetic factors and environmental stimuli interact to cause genetic and epigenetic aberrations in human cells. Mutations in the germline act as either high-penetra ...[more]

PMID: 24875441

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Project description:MicroRNAs (miRNAs) are key post-transcriptional regulators that affect protein translation by targeting mRNAs. Their role in disease etiology and toxicity are well recognized. Given the rapid advancement of next-generation sequencing techniques, miRNA profiling has been increasingly conducted with RNA-seq, namely miRNA-seq. Analysis of miRNA-seq data requires several steps: (1) mapping the reads to miRBase, (2) considering mismatches during the hairpin alignment (windowing), and (3) counting the reads (quantification). The choice made in each step with respect to the parameter settings could affect miRNA quantification, differentially expressed miRNAs (DEMs) detection and novel miRNA identification. Furthermore, these parameters do not act in isolation and their joint effects impact miRNA-seq results and interpretation. In toxicogenomics, the variation associated with parameter setting should not overpower the treatment effect (such as the dose/time-dependent effect). In this study, four commonly used miRNA-seq analysis tools (i.e., miRDeep2, miRExpress, miRNAkey, sRNAbench) were comparatively evaluated with a standard toxicogenomics study design. We tested 30 different parameter settings on miRNA-seq data generated from thioacetamide-treated rat liver samples for three dose levels across four time points, followed by four normalization options. Because both miRExpress and miRNAkey yielded larger variation than that of the treatment effects across multiple parameter settings, our analyses mainly focused on the side-by-side comparison between miRDeep2 and sRNAbench. While the number of miRNAs detected by miRDeep2 was almost the subset of those detected by sRNAbench, the number of DEMs identified by both tools was comparable under the same parameter settings and normalization method. Change in the number of nucleotides out of the mature sequence in the hairpin alignment (window option) yielded the largest variation for miRNA quantification and DEMs detection. However, such a variation is relatively small compared to the treatment effect when the study focused on DEMs that are more critical to interpret the toxicological effect. While the normalization methods introduced a large variation in DEMs, toxic behavior of thioacetamide showed consistency in the trend of time-dose responses. Overall, miRDeep2 was found to be preferable over other choices when the window option allowed up to three nucleotides from both ends.

Dataset Information

Toxicogenomics and cancer susceptibility: advances with next-generation sequencing.

Publications

Toxicogenomics and cancer susceptibility: advances with next-generation sequencing.

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