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Robust identification of significant interactions between toxicogenomic biomarkers and their regulatory chemical compounds using logistic moving range chart
Institution:1. Rangeland Scientist and Research Leader, US Dept of Agriculture–Agricultural Research Service–Rangeland Resources Research Unit, Cheyenne, WY 82009, USA;2. Post-doctoral Research Associate, US Dept of Agriculture–Agricultural Research Service–Rangeland Resources Research Unit, Cheyenne, WY 82009, USA;3. Physical Science Technician, US Dept of Agriculture–Agricultural Research Service–Rangeland Resources Research Unit, Cheyenne, WY 82009, USA;4. Area Statistician US Dept of Agriculture–Agricultural Research Service–Plains Area, Fort Collins, CO 80526, USA;5. Agronomist Cátedra de Forrajicultura, IFEVA, Facultad de Agronomía, Universidad de Buenos Aires, CONICET, C1417DSE, Buenos Aries, Argentina;6. Agronomist, Instituto Nacional de Tecnología Agropecuaria (INTA), Estación Experimental Concepción del Uruguay, Entre Ríos, Argentina
Abstract:Identification of significant interactions between genes and chemical compounds/drugs is an important issue in toxicogenomic studies as well as in drug discovery and development. There are some online and offline computational tools for toxicogenomic data analysis to identify the biomarker genes and their regulatory chemical compounds/drugs. However, none of the researchers has considered yet the identification of significant interactions between genes and compounds. Therefore, in this paper, we have discussed two approaches namely moving range chart (MRC) and logistic moving range chart (LMRC) for the identification of significant up-regulatory (UpR) and down-regulatory (DnR) gene-compound interactions as well as toxicogenomic biomarkers and their regulatory chemical compounds/drugs. We have investigated the performance of both MRC and LMRC approaches using simulated datasets. Simulation results show that both approaches perform almost equally in absence of outliers. However, in presence of outliers, the LMRC shows much better performance than the MRC. In case of real life toxicogenomic data analysis, the proposed LMRC approach detected some important down-regulated biomarker genes those were not detected by other approaches. Therefore, in this paper, our proposal is to use LMRC for robust identification of significant interactions between genes and chemical compounds/drugs.
Keywords:Toxicogenomic data  Gene-compound interaction  Fold change gene expression  Logistic transformation  Moving range chart
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