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      Statistical and Machine-Learning Analyses in Nutritional Genomics Studies

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          Abstract

          Nutritional compounds may have an influence on different OMICs levels, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and metagenomics. The integration of OMICs data is challenging but may provide new knowledge to explain the mechanisms involved in the metabolism of nutrients and diseases. Traditional statistical analyses play an important role in description and data association; however, these statistical procedures are not sufficiently enough powered to interpret the large integrated multiple OMICs (multi-OMICS) datasets. Machine learning (ML) approaches can play a major role in the interpretation of multi-OMICS in nutrition research. Specifically, ML can be used for data mining, sample clustering, and classification to produce predictive models and algorithms for integration of multi-OMICs in response to dietary intake. The objective of this review was to investigate the strategies used for the analysis of multi-OMICs data in nutrition studies. Sixteen recent studies aimed to understand the association between dietary intake and multi-OMICs data are summarized. Multivariate analysis in multi-OMICs nutrition studies is used more commonly for analyses. Overall, as nutrition research incorporated multi-OMICs data, the use of novel approaches of analysis such as ML needs to complement the traditional statistical analyses to fully explain the impact of nutrition on health and disease.

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          Most cited references80

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          Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

          MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. The majority of miRNAs are transcribed from DNA sequences into primary miRNAs and processed into precursor miRNAs, and finally mature miRNAs. In most cases, miRNAs interact with the 3′ untranslated region (3′ UTR) of target mRNAs to induce mRNA degradation and translational repression. However, interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, have also been reported. Under certain conditions, miRNAs can also activate translation or regulate transcription. The interaction of miRNAs with their target genes is dynamic and dependent on many factors, such as subcellular location of miRNAs, the abundancy of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes. Extracellular miRNAs function as chemical messengers to mediate cell-cell communication. In this review, we provide an update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations. We also summarize the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs.
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            Personalized Nutrition by Prediction of Glycemic Responses.

            Elevated postprandial blood glucose levels constitute a global epidemic and a major risk factor for prediabetes and type II diabetes, but existing dietary methods for controlling them have limited efficacy. Here, we continuously monitored week-long glucose levels in an 800-person cohort, measured responses to 46,898 meals, and found high variability in the response to identical meals, suggesting that universal dietary recommendations may have limited utility. We devised a machine-learning algorithm that integrates blood parameters, dietary habits, anthropometrics, physical activity, and gut microbiota measured in this cohort and showed that it accurately predicts personalized postprandial glycemic response to real-life meals. We validated these predictions in an independent 100-person cohort. Finally, a blinded randomized controlled dietary intervention based on this algorithm resulted in significantly lower postprandial responses and consistent alterations to gut microbiota configuration. Together, our results suggest that personalized diets may successfully modify elevated postprandial blood glucose and its metabolic consequences. VIDEO ABSTRACT.
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              The Chi-square test of independence

              The Chi-square statistic is a non-parametric (distribution free) tool designed to analyze group differences when the dependent variable is measured at a nominal level. Like all non-parametric statistics, the Chi-square is robust with respect to the distribution of the data. Specifically, it does not require equality of variances among the study groups or homoscedasticity in the data. It permits evaluation of both dichotomous independent variables, and of multiple group studies. Unlike many other non-parametric and some parametric statistics, the calculations needed to compute the Chi-square provide considerable information about how each of the groups performed in the study. This richness of detail allows the researcher to understand the results and thus to derive more detailed information from this statistic than from many others. The Chi-square is a significance statistic, and should be followed with a strength statistic. The Cramer’s V is the most common strength test used to test the data when a significant Chi-square result has been obtained. Advantages of the Chi-square include its robustness with respect to distribution of the data, its ease of computation, the detailed information that can be derived from the test, its use in studies for which parametric assumptions cannot be met, and its flexibility in handling data from both two group and multiple group studies. Limitations include its sample size requirements, difficulty of interpretation when there are large numbers of categories (20 or more) in the independent or dependent variables, and tendency of the Cramer’s V to produce relative low correlation measures, even for highly significant results.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                14 October 2020
                October 2020
                : 12
                : 10
                : 3140
                Affiliations
                [1 ]Endocrinology and Nephrology Unit, CHU de Québec-Laval University Research Center, Quebec (PQ), QC G1V 4G2, Canada; leila.khorraminezhad.1@ 123456ulaval.ca (L.K.); mickael.leclercq@ 123456crchudequebec.ulaval.ca (M.L.); Arnaud.Droit@ 123456crchudequebec.ulaval.ca (A.D.); Jean-Francois.Bilodeau@ 123456crchudequebec.ulaval.ca (J.-F.B.)
                [2 ]Department of Molecular Medicine, Faculty of Medicine, Laval University, Quebec (PQ), QC G1V 0A6, Canada
                [3 ]Department of Medicine, Faculty of Medicine, Laval University, Quebec (PQ), QC G1V 0A6, Canada
                [4 ]Department of Kinesiology, Faculty of Medicine, Laval University, Quebec (PQ), QC G1V 0A6, Canada
                Author notes
                [* ]Correspondence: Iwona.Rudkowska@ 123456crchudequebec.ulaval.ca ; Tel.: +1-418-525-4444 (ext. 46380)
                Author information
                https://orcid.org/0000-0001-6205-888X
                https://orcid.org/0000-0001-7922-790X
                Article
                nutrients-12-03140
                10.3390/nu12103140
                7602401
                33066636
                f02fda28-e1f1-42ab-bba2-c5d6fabe31eb
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 September 2020
                : 10 October 2020
                Categories
                Review

                Nutrition & Dietetics
                genomics,multi-omics,machine learning,data integration,nutrition
                Nutrition & Dietetics
                genomics, multi-omics, machine learning, data integration, nutrition

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