Dataset Information

Ensemble of rankers for efficient gene signature extraction in smoke exposure classification.

ABSTRACT: BACKGROUND:System toxicology aims at understanding the mechanisms used by biological systems to respond to toxicants. Such understanding can be leveraged to assess the risk of chemicals, drugs, and consumer products in living organisms. In system toxicology, machine learning techniques and methodologies are applied to develop prediction models for classification of toxicant exposure of biological systems. Gene expression data (RNA/DNA microarray) are often used to develop such prediction models. RESULTS:The outcome of the present work is an experimental methodology to develop prediction models, based on robust gene signatures, for the classification of cigarette smoke exposure and cessation in humans. It is a result of the participation in the recent sbv IMPROVER SysTox Computational Challenge. By merging different gene selection techniques, we obtain robust gene signatures and we investigate prediction capabilities of different off-the-shelf machine learning techniques, such as artificial neural networks, linear models and support vector machines. We also predict six novel genes in our signature, and firmly believe these genes have to be further investigated as biomarkers for tobacco smoking exposure. CONCLUSIONS:The proposed methodology provides gene signatures with top-ranked performances in the prediction of the investigated classification methods, as well as new discoveries in genetic signatures for bio-markers of the smoke exposure of humans.

SUBMITTER: Giordano M

PROVIDER: S-EPMC5850943 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Ensemble of rankers for efficient gene signature extraction in smoke exposure classification.

Giordano Maurizio M Tripathi Kumar Parijat KP Guarracino Mario Rosario MR

BMC bioinformatics 20180308 Suppl 2

<h4>Background</h4>System toxicology aims at understanding the mechanisms used by biological systems to respond to toxicants. Such understanding can be leveraged to assess the risk of chemicals, drugs, and consumer products in living organisms. In system toxicology, machine learning techniques and methodologies are applied to develop prediction models for classification of toxicant exposure of biological systems. Gene expression data (RNA/DNA microarray) are often used to develop such prediction ...[more]

PMID: 29536823

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Project description:BACKGROUND:MicroRNAs (miRNAs) are noncoding RNA molecules heavily involved in human tumors, in which few of them circulating the human body. Finding a tumor-associated signature of miRNA, that is, the minimum miRNA entities to be measured for discriminating both different types of cancer and normal tissues, is of utmost importance. Feature selection techniques applied in machine learning can help however they often provide naive or biased results. RESULTS:An ensemble feature selection strategy for miRNA signatures is proposed. miRNAs are chosen based on consensus on feature relevance from high-accuracy classifiers of different typologies. This methodology aims to identify signatures that are considerably more robust and reliable when used in clinically relevant prediction tasks. Using the proposed method, a 100-miRNA signature is identified in a dataset of 8023 samples, extracted from TCGA. When running eight-state-of-the-art classifiers along with the 100-miRNA signature against the original 1046 features, it could be detected that global accuracy differs only by 1.4%. Importantly, this 100-miRNA signature is sufficient to distinguish between tumor and normal tissues. The approach is then compared against other feature selection methods, such as UFS, RFE, EN, LASSO, Genetic Algorithms, and EFS-CLA. The proposed approach provides better accuracy when tested on a 10-fold cross-validation with different classifiers and it is applied to several GEO datasets across different platforms with some classifiers showing more than 90% classification accuracy, which proves its cross-platform applicability. CONCLUSIONS:The 100-miRNA signature is sufficiently stable to provide almost the same classification accuracy as the complete TCGA dataset, and it is further validated on several GEO datasets, across different types of cancer and platforms. Furthermore, a bibliographic analysis confirms that 77 out of the 100 miRNAs in the signature appear in lists of circulating miRNAs used in cancer studies, in stem-loop or mature-sequence form. The remaining 23 miRNAs offer potentially promising avenues for future research.

Dataset Information

Ensemble of rankers for efficient gene signature extraction in smoke exposure classification.

Publications

Ensemble of rankers for efficient gene signature extraction in smoke exposure classification.

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