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Abstract:
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Drug dosage considerations are vital to personalized treatment plans. However, many drug dose response studies are based on adult populations. Dosage guidelines for children are often extrapolated by size or weight. Many drugs are metabolized through the liver; understanding the ontogeny of the liver may contribute to development of drug-dosing guidelines for children. We aim to apply an integrative transcriptome-metabolome approach to gain insights into the ontogeny of liver function using pediatric liver samples that span from newborn to adolescent. First, a stepwise univariate integrative analysis approach was conducted to identify genes and metabolites that were associated with age. Next, to reduce the amount of multiple testing, both genes and metabolites were grouped into modules derived from the topographical overlap matrix. After construction of the modules, each module was summarized by the first principal component and finally module association analysis was completed. Combining genes/metabolites into modules leads to a more impactful interpretation than studying a single gene/metabolite association, thus potentially leading to new understanding of ontogeny of the liver.
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