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      NFnetFu: A novel workflow for microbiome data fusion

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          Abstract

          Microbiome data analysis and its interpretation into meaningful biological insights remain very challenging for numerous reasons, perhaps most prominently, due to the need to account for multiple factors, including collinearity, sparsity (excessive zeros) and effect size, that the complex experimental workflow and subsequent downstream data analysis require. Moreover, a meaningful microbiome data analysis necessitates the development of interpretable models that incorporate inferences across available data as well as background biomedical knowledge. We developed a multimodal framework that considers sparsity (excessive zeros), lower effect size, intrinsically microbial correlations, i.e., collinearity, as well as background biomedical knowledge in the form of a cluster-infused enriched network architecture. Finally, our framework also provides a candidate taxa/Operational Taxonomic Unit (OTU) that can be targeted for future validation experiments. We have developed a tool, the term NFnetFU (Neuro Fuzzy network Fusion), that encompasses our framework and have made it freely available at https://github.com/VartikaBisht6197/NFnetFu.

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          Highlights

          • Microbiome data set have many challenges including collinearity, sparsity (excessive zeros) and effect size.

          • A sequential workflow and downstream data analysis is required to capture knowledge from each step.

          • We developed a microbiome enrichment based fusion score called “ NFnetFu” to facilitate data analysis.

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          Most cited references79

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          Metagenomic biomarker discovery and explanation

          This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.
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            Regression Shrinkage and Selection Via the Lasso

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              Role of the microbiota in immunity and inflammation.

              The microbiota plays a fundamental role on the induction, training, and function of the host immune system. In return, the immune system has largely evolved as a means to maintain the symbiotic relationship of the host with these highly diverse and evolving microbes. When operating optimally, this immune system-microbiota alliance allows the induction of protective responses to pathogens and the maintenance of regulatory pathways involved in the maintenance of tolerance to innocuous antigens. However, in high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses. This phenomenon is proposed to account for some of the dramatic rise in autoimmune and inflammatory disorders in parts of the world where our symbiotic relationship with the microbiota has been the most affected. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Comput Biol Med
                Comput Biol Med
                Computers in Biology and Medicine
                Elsevier
                0010-4825
                1879-0534
                1 August 2021
                August 2021
                : 135
                : 104556
                Affiliations
                [a ]College of Medical and Dental Sciences, Institute of Cancer and Genomic Sciences, Centre for Computational Biology, University of Birmingham, B15 2TT, UK
                [b ]Institute of Translational Medicine, University Hospitals Birmingham NHS, Foundation Trust, B15 2TT, UK
                [c ]NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospital Birmingham, Birmingham, B15 2WB, UK
                [d ]MRC Health Data Research UK HDR, UK
                [e ]NIHR Experimental Cancer Medicine Centre, B15 2TT, Birmingham, UK
                [f ]NIHR Biomedical Research Centre, University Hospital Birmingham, Birmingham, B15 2TT, UK
                Author notes
                []Corresponding author. University of Birmingham, B15 2TT, UK. a.acharjee@ 123456bham.ac.uk
                [1]

                These authors made equal contributions.

                Article
                S0010-4825(21)00350-4 104556
                10.1016/j.compbiomed.2021.104556
                8404037
                34216888
                5ba76071-213f-49e1-b3c9-85794fb86737
                © 2021 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 7 February 2021
                : 4 June 2021
                : 4 June 2021
                Categories
                Article

                microbiome,fuzzy inference,clustering,network fusion
                microbiome, fuzzy inference, clustering, network fusion

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