Binary Metabolic Phenotypes and Phenotype Diversity Metrics for the Functional Characterization of Microbial Communities
The profiling of 16S rRNA revolutionized the exploration of microbiomes, allowing to describe community composition by enumerating relevant taxa and their abundances. However, taxonomic profiles alone lack interpretability in terms of bacterial metabolism, and their translation into functional chara...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.653314/full |
| _version_ | 1818864021670985728 |
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| author | Stanislav N. Iablokov Pavel S. Novichkov Andrei L. Osterman Dmitry A. Rodionov Dmitry A. Rodionov |
| author_facet | Stanislav N. Iablokov Pavel S. Novichkov Andrei L. Osterman Dmitry A. Rodionov Dmitry A. Rodionov |
| author_sort | Stanislav N. Iablokov |
| collection | DOAJ |
| description | The profiling of 16S rRNA revolutionized the exploration of microbiomes, allowing to describe community composition by enumerating relevant taxa and their abundances. However, taxonomic profiles alone lack interpretability in terms of bacterial metabolism, and their translation into functional characteristics of microbiomes is a challenging task. This bottom-up approach minimally requires a reference collection of major metabolic traits deduced from the complete genomes of individual organisms, an accurate method of projecting these traits from a reference collection to the analyzed amplicon sequence variants (ASVs), and, ultimately, an approach to a microbiome-wide aggregation of predicted individual traits into physiologically relevant cumulative metrics to characterize and compare multiple microbiome samples. In this study, we extended a previously introduced computational approach for the functional profiling of complex microbial communities, which is based on the concept of binary metabolic phenotypes encoding the presence (“1”) or absence (“0”) of various measurable physiological properties in individual organisms that are termed phenotype carriers or non-carriers, respectively. Derived from complete genomes via metabolic reconstruction, binary phenotypes provide a foundation for the prediction of functional traits for each ASV identified in a microbiome sample. Here, we introduced three distinct mapping schemes for a microbiome-wide phenotype prediction and assessed their accuracy on the 16S datasets of mock bacterial communities representing human gut microbiome (HGM) as well as on two large HGM datasets, the American Gut Project and the UK twins study. The 16S sequence-based scheme yielded a more accurate phenotype predictions, while the taxonomy-based schemes demonstrated a reasonable performance to warrant their application for other types of input data (e.g., from shotgun metagenomics or qPCR). In addition to the abundance-weighted Community Phenotype Indices (CPIs) reflecting the fractional representation of various phenotype carriers in microbiome samples, we employ metrics capturing the diversity of phenotype carriers, Phenotype Alpha Diversity (PAD) and Phenotype Beta Diversity (PBD). In combination with CPI, PAD allows to classify the robustness of metabolic phenotypes by their anticipated stability in the face of potential environmental perturbations. PBD provides a promising approach for detecting the metabolic features potentially contributing to disease-associated metabolic traits as illustrated by a comparative analysis of HGM samples from healthy and Crohn’s disease cohorts. |
| first_indexed | 2024-12-19T10:25:02Z |
| format | Article |
| id | doaj.art-a21da3cb636742ea8f0179358f0eae1b |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-19T10:25:02Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-a21da3cb636742ea8f0179358f0eae1b2022-12-21T20:25:56ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-05-011210.3389/fmicb.2021.653314653314Binary Metabolic Phenotypes and Phenotype Diversity Metrics for the Functional Characterization of Microbial CommunitiesStanislav N. Iablokov0Pavel S. Novichkov1Andrei L. Osterman2Dmitry A. Rodionov3Dmitry A. Rodionov4A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, RussiaPhenoBiome Inc., Walnut Creek, CA, United StatesSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United StatesA.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, RussiaSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United StatesThe profiling of 16S rRNA revolutionized the exploration of microbiomes, allowing to describe community composition by enumerating relevant taxa and their abundances. However, taxonomic profiles alone lack interpretability in terms of bacterial metabolism, and their translation into functional characteristics of microbiomes is a challenging task. This bottom-up approach minimally requires a reference collection of major metabolic traits deduced from the complete genomes of individual organisms, an accurate method of projecting these traits from a reference collection to the analyzed amplicon sequence variants (ASVs), and, ultimately, an approach to a microbiome-wide aggregation of predicted individual traits into physiologically relevant cumulative metrics to characterize and compare multiple microbiome samples. In this study, we extended a previously introduced computational approach for the functional profiling of complex microbial communities, which is based on the concept of binary metabolic phenotypes encoding the presence (“1”) or absence (“0”) of various measurable physiological properties in individual organisms that are termed phenotype carriers or non-carriers, respectively. Derived from complete genomes via metabolic reconstruction, binary phenotypes provide a foundation for the prediction of functional traits for each ASV identified in a microbiome sample. Here, we introduced three distinct mapping schemes for a microbiome-wide phenotype prediction and assessed their accuracy on the 16S datasets of mock bacterial communities representing human gut microbiome (HGM) as well as on two large HGM datasets, the American Gut Project and the UK twins study. The 16S sequence-based scheme yielded a more accurate phenotype predictions, while the taxonomy-based schemes demonstrated a reasonable performance to warrant their application for other types of input data (e.g., from shotgun metagenomics or qPCR). In addition to the abundance-weighted Community Phenotype Indices (CPIs) reflecting the fractional representation of various phenotype carriers in microbiome samples, we employ metrics capturing the diversity of phenotype carriers, Phenotype Alpha Diversity (PAD) and Phenotype Beta Diversity (PBD). In combination with CPI, PAD allows to classify the robustness of metabolic phenotypes by their anticipated stability in the face of potential environmental perturbations. PBD provides a promising approach for detecting the metabolic features potentially contributing to disease-associated metabolic traits as illustrated by a comparative analysis of HGM samples from healthy and Crohn’s disease cohorts.https://www.frontiersin.org/articles/10.3389/fmicb.2021.653314/fullpredictive functional profilingmetagenomic16S rRNA sequencingmetabolic phenotypesmicrobiomephenotype diversity |
| spellingShingle | Stanislav N. Iablokov Pavel S. Novichkov Andrei L. Osterman Dmitry A. Rodionov Dmitry A. Rodionov Binary Metabolic Phenotypes and Phenotype Diversity Metrics for the Functional Characterization of Microbial Communities Frontiers in Microbiology predictive functional profiling metagenomic 16S rRNA sequencing metabolic phenotypes microbiome phenotype diversity |
| title | Binary Metabolic Phenotypes and Phenotype Diversity Metrics for the Functional Characterization of Microbial Communities |
| title_full | Binary Metabolic Phenotypes and Phenotype Diversity Metrics for the Functional Characterization of Microbial Communities |
| title_fullStr | Binary Metabolic Phenotypes and Phenotype Diversity Metrics for the Functional Characterization of Microbial Communities |
| title_full_unstemmed | Binary Metabolic Phenotypes and Phenotype Diversity Metrics for the Functional Characterization of Microbial Communities |
| title_short | Binary Metabolic Phenotypes and Phenotype Diversity Metrics for the Functional Characterization of Microbial Communities |
| title_sort | binary metabolic phenotypes and phenotype diversity metrics for the functional characterization of microbial communities |
| topic | predictive functional profiling metagenomic 16S rRNA sequencing metabolic phenotypes microbiome phenotype diversity |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.653314/full |
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