Assessing and Interpreting the Metagenome Heterogeneity With Power Law

There are two major sequencing technologies for investigating the microbiome: the amplicon sequencing that generates the OTU (operational taxonomic unit) tables of marker genes (e.g., bacterial 16S-rRNA), and the metagenomic shotgun sequencing that generates metagenomic gene abundance (MGA) tables....

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Main Author: Zhanshan (Sam) Ma
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-05-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmicb.2020.00648/full
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author Zhanshan (Sam) Ma
Zhanshan (Sam) Ma
author_facet Zhanshan (Sam) Ma
Zhanshan (Sam) Ma
author_sort Zhanshan (Sam) Ma
collection DOAJ
description There are two major sequencing technologies for investigating the microbiome: the amplicon sequencing that generates the OTU (operational taxonomic unit) tables of marker genes (e.g., bacterial 16S-rRNA), and the metagenomic shotgun sequencing that generates metagenomic gene abundance (MGA) tables. The OTU table is the counterpart of species abundance tables in macrobial ecology of plants and animals, and has been the target of numerous ecological and network analyses in recent gold rush for microbiome research and in great efforts for establishing an inclusive theoretical ecology. Nevertheless, MGA analyses have been largely limited to bioinformatics pipelines and ad hoc statistical methods, and systematic approaches to MGAs guided by classic ecological theories are still few. Here, we argue that, the difference between “gene kinds” and “gene species” are nominal, and the metagenome that a microbiota carries is essentially a ‘community’ of metagenomic genes (MGs). Each row of a MGA table represents a metagenome of a microbiota, and the whole MGA table represents a ‘meta-metagenome’ (or an assemblage of metagenomes) of N microbiotas (microbiome samples). Consequently, the same ecological/network analyses used in OTU analyses should be equally applicable to MGA tables. Here we choose to analyze the heterogeneity of metagenome by introducing classic Taylor’s power law (TPL) and its recent extensions in community ecology. Heterogeneity is a fundamental property of metagenome, particularly in the context of human microbiomes. Recent studies have shown that the heterogeneity of human metagenomes is far more significant than that of human genomes. Therefore, without deep understanding of the human metagenome heterogeneity, personalized medicine of the human microbiome-associated diseases is hardly feasible. The TPL extensions have been successfully applied to measure the heterogeneity of human microbiome based on amplicon-sequencing reads of marker genes (e.g., 16s-rRNA). In this article, we demonstrate the analysis of the metagenomic heterogeneity of human gut microbiome at whole metagenome scale (with type-I power law extension) and metagenomic gene scale (type-III), as well as the heterogeneity of gene clusters, respectively. We further examine the influences of obesity, IBD and diabetes on the heterogeneity, which is of important ramifications for the diagnosis and treatment of human microbiome-associated diseases.
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spelling doaj.art-a759428e0959400191ca895ad437a5b72022-12-22T00:14:07ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-05-011110.3389/fmicb.2020.00648482255Assessing and Interpreting the Metagenome Heterogeneity With Power LawZhanshan (Sam) Ma0Zhanshan (Sam) Ma1Computational Biology and Medical Ecology Lab, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, ChinaCenter for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, ChinaThere are two major sequencing technologies for investigating the microbiome: the amplicon sequencing that generates the OTU (operational taxonomic unit) tables of marker genes (e.g., bacterial 16S-rRNA), and the metagenomic shotgun sequencing that generates metagenomic gene abundance (MGA) tables. The OTU table is the counterpart of species abundance tables in macrobial ecology of plants and animals, and has been the target of numerous ecological and network analyses in recent gold rush for microbiome research and in great efforts for establishing an inclusive theoretical ecology. Nevertheless, MGA analyses have been largely limited to bioinformatics pipelines and ad hoc statistical methods, and systematic approaches to MGAs guided by classic ecological theories are still few. Here, we argue that, the difference between “gene kinds” and “gene species” are nominal, and the metagenome that a microbiota carries is essentially a ‘community’ of metagenomic genes (MGs). Each row of a MGA table represents a metagenome of a microbiota, and the whole MGA table represents a ‘meta-metagenome’ (or an assemblage of metagenomes) of N microbiotas (microbiome samples). Consequently, the same ecological/network analyses used in OTU analyses should be equally applicable to MGA tables. Here we choose to analyze the heterogeneity of metagenome by introducing classic Taylor’s power law (TPL) and its recent extensions in community ecology. Heterogeneity is a fundamental property of metagenome, particularly in the context of human microbiomes. Recent studies have shown that the heterogeneity of human metagenomes is far more significant than that of human genomes. Therefore, without deep understanding of the human metagenome heterogeneity, personalized medicine of the human microbiome-associated diseases is hardly feasible. The TPL extensions have been successfully applied to measure the heterogeneity of human microbiome based on amplicon-sequencing reads of marker genes (e.g., 16s-rRNA). In this article, we demonstrate the analysis of the metagenomic heterogeneity of human gut microbiome at whole metagenome scale (with type-I power law extension) and metagenomic gene scale (type-III), as well as the heterogeneity of gene clusters, respectively. We further examine the influences of obesity, IBD and diabetes on the heterogeneity, which is of important ramifications for the diagnosis and treatment of human microbiome-associated diseases.https://www.frontiersin.org/article/10.3389/fmicb.2020.00648/fullmetagenome ecologymetagenomic gene abundance (MGA) tableTaylor’s power lawpower law extensionsmetagenome spatial heterogeneitymetagenome functional gene cluster (MFGC)
spellingShingle Zhanshan (Sam) Ma
Zhanshan (Sam) Ma
Assessing and Interpreting the Metagenome Heterogeneity With Power Law
Frontiers in Microbiology
metagenome ecology
metagenomic gene abundance (MGA) table
Taylor’s power law
power law extensions
metagenome spatial heterogeneity
metagenome functional gene cluster (MFGC)
title Assessing and Interpreting the Metagenome Heterogeneity With Power Law
title_full Assessing and Interpreting the Metagenome Heterogeneity With Power Law
title_fullStr Assessing and Interpreting the Metagenome Heterogeneity With Power Law
title_full_unstemmed Assessing and Interpreting the Metagenome Heterogeneity With Power Law
title_short Assessing and Interpreting the Metagenome Heterogeneity With Power Law
title_sort assessing and interpreting the metagenome heterogeneity with power law
topic metagenome ecology
metagenomic gene abundance (MGA) table
Taylor’s power law
power law extensions
metagenome spatial heterogeneity
metagenome functional gene cluster (MFGC)
url https://www.frontiersin.org/article/10.3389/fmicb.2020.00648/full
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