Dataset Information

Beyond Taxonomic Analysis of Microbiomes: A Functional Approach for Revisiting Microbiome Changes in Colorectal Cancer.

ABSTRACT: Colorectal cancer (CRC) is one of the most prevalent cancers in the world, especially in developed countries. In different studies, the association between CRC and dysbiosis of gut microbiome has been reported. However, most of these works focus on the taxonomic variation of the microbiome, which presents little, if any, functional insight about the reason behind and/or consequences of microbiome dysbiosis. In this study, we used a previously reported metagenome dataset which is obtained by sequencing 156 microbiome samples of healthy individuals as the control group (Co), as well as microbiome samples of patients with advanced colorectal adenoma (Ad) and colorectal carcinoma (Ca). Features of the microbiome samples have been analyzed at the level of species, as well as four functional levels, i.e., gene, KEGG orthology (KO) group, Enzyme Commission (EC) number, and reaction. It was shown that, at each of these levels, certain features exist which show significant changing trends during cancer progression. In the next step, a list of these features were extracted, which were shown to be able to predict the category of Co, Ad, and Ca samples with an accuracy of >85%. When only one group of features (species, gene, KO group, EC number, reaction) was used, KO-related features were found to be the most successful features for classifying the three categories of samples. Notably, species-related features showed the least success in sample classification. Furthermore, by applying an independent test set, we showed that these performance trends are not limited to our original dataset. We determined the most important classification features at each of the four functional levels. We propose that these features can be considered as biomarkers of CRC progression. Finally, we show that the intra-diversity of each sample at the levels of bacterial species and genes is much more than those of the KO groups, EC numbers, and reactions of that sample. Therefore, we conclude that the microbiome diversity at the species level, or gene level, is not necessarily associated with the diversity at the functional level, which again indicates the importance of KO-, EC-, and reaction-based features in metagenome analysis. The source code of proposed method is freely available from https://www.bioinformatics.org/mamed.

SUBMITTER: Norouzi-Beirami MH

PROVIDER: S-EPMC6990412 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Beyond Taxonomic Analysis of Microbiomes: A Functional Approach for Revisiting Microbiome Changes in Colorectal Cancer.

Norouzi-Beirami Mohammad Hossein MH Marashi Sayed-Amir SA Banaei-Moghaddam Ali Mohammad AM Kavousi Kaveh K

Frontiers in microbiology 20200123

Colorectal cancer (CRC) is one of the most prevalent cancers in the world, especially in developed countries. In different studies, the association between CRC and dysbiosis of gut microbiome has been reported. However, most of these works focus on the taxonomic variation of the microbiome, which presents little, if any, functional insight about the reason behind and/or consequences of microbiome dysbiosis. In this study, we used a previously reported metagenome dataset which is obtained by sequ ...[more]

PMID: 32038558

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Project description:Exploring microbial community compositions in humans with healthy versus diseased states is crucial to understand the microbe-host interplay associated with the disease progression. Although the relationship between oral cancer and microbiome was previously established, it remained controversial, and yet the ecological characteristics and their responses to oral carcinogenesis have not been well studied. Here, using the bacterial 16S rRNA gene amplicon sequencing along with the in silico function analysis by PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2), we systematically characterized the compositions and the ecological drivers of saliva microbiome in the cohorts of orally healthy, non-recurrent oral verrucous hyperplasia (a pre-cancer lesion), and oral verrucous hyperplasia-associated oral cancer at taxonomic and function levels, and compared them with the re-analysis of publicly available datasets. Diversity analyses showed that microbiome dysbiosis in saliva was significantly linked to oral health status. As oral health deteriorated, the number of core species declined, and metabolic pathways predicted by PICRUSt2 were dysregulated. Partitioned beta-diversity revealed an extremely high species turnover but low function turnover. Functional beta-diversity in saliva microbiome shifted from turnover to nestedness during oral carcinogenesis, which was not observed at taxonomic levels. Correspondingly, the quantitative analysis of stochasticity ratios showed that drivers of microbial composition and functional gene content of saliva microbiomes were primarily governed by the stochastic processes, yet the driver of functional gene content shifted toward deterministic processes as oral cancer developed. Re-analysis of publicly accessible datasets supported not only the distinctive family taxa of Veillonellaceae and Actinomycetaceae present in normal cohorts but also that Flavobacteriaceae and Peptostreptococcaceae as well as the dysregulated metabolic pathways of nucleotides, amino acids, fatty acids, and cell structure were related to oral cancer. Using predicted functional profiles to elucidate the correlations to the oral health status shows superior performance than using taxonomic data among different studies. These findings advance our understanding of the oral ecosystem in relation to oral carcinogenesis and provide a new direction to the development of microbiome-based tools to study the interplay of the oral microbiome, metabolites, and host health.

Project description:Colorectal cancer is a common and deadly disease in the United States accounting for over 50,000 deaths in 2020. This progressive disease is highly preventable with early detection and treatment, but many people do not comply with the recommended screening guidelines. The gut microbiome has emerged as a promising target for noninvasive detection of colorectal cancer. Most microbiome-based classification efforts utilize taxonomic abundance data from operational taxonomic units (OTUs) or amplicon sequence variants (ASVs) with the goal of increasing taxonomic resolution. However, it is unknown which taxonomic resolution is optimal for microbiome-based classification of colorectal cancer. To address this question, we used a reproducible machine learning framework to quantify classification performance of models based on data annotated to phylum, class, order, family, genus, OTU, and ASV levels. We found that model performance increased with increasing taxonomic resolution, up to the family level where performance was equal (P > 0.05) among family (mean area under the receiver operating characteristic curve [AUROC], 0.689), genus (mean AUROC, 0.690), and OTU (mean AUROC, 0.693) levels before decreasing at the ASV level (P < 0.05; mean AUROC, 0.676). These results demonstrate a trade-off between taxonomic resolution and prediction performance, where coarse taxonomic resolution (e.g., phylum) is not distinct enough, but fine resolution (e.g., ASV) is too individualized to accurately classify samples. Similar to the story of Goldilocks and the three bears (L. B. Cauley, Goldilocks and the Three Bears, 1981), mid-range resolution (i.e., family, genus, and OTU) is "just right" for optimal prediction of colorectal cancer from microbiome data. IMPORTANCE Despite being highly preventable, colorectal cancer remains a leading cause of cancer-related death in the United States. Low-cost, noninvasive detection methods could greatly improve our ability to identify and treat early stages of disease. The microbiome has shown promise as a resource for detection of colorectal cancer. Research on the gut microbiome tends to focus on improving our ability to profile species and strain level taxonomic resolution. However, we found that finer resolution impedes the ability to predict colorectal cancer based on the gut microbiome. These results highlight the need for consideration of the appropriate taxonomic resolution for microbiome analyses and that finer resolution is not always more informative.

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Project description:The taxonomic composition and diversity of tick midgut microbiota have been extensively studied in different species of the genera Rhipicephalus, Ixodes, Amblyomma, Haemaphysalis, Hyalomma, Dermacentor, Argas and Ornithodoros, while the functional significance of bacterial diversity has been proportionally less explored. In this study, we used previously published 16S amplicon sequence data sets from three Ixodes scapularis cohorts, two of uninfected nymphs, and one of larvae experimentally infected with Borrelia burgdorferi, to test the functional redundancy of the tick microbiome. We predicted the metabolic profiling of each sample using the state-of-the-art metagenomics tool PICRUSt2. The results showed that the microbiomes of all I. scapularis samples share only 80 taxa (24.6%, total 324), while out of the 342 metabolic pathways predicted, 82.7%, were shared by all the ticks. Borrelia-infected larvae lack 15.4% of pathways found in the microbiome of uninfected nymphs. Taxa contribution analysis showed that the functional microbiome of uninfected ticks was highly redundant, with, in some cases, up to 198 bacterial taxa contributing to a single pathway. However, Borrelia-infected larvae had a smaller redundancy with 6.7% of pathways provided by more than 100 genera, while 15.7-19.2% of pathways were provided by more than 100 genera in the two cohorts of uninfected ticks. In addition, we compared the functional profiles of three microbial communities from each data set, identified through a network-based approach, and we observed functional similarity between them. Based on the functional redundancy and functional similarity of the microbiome of ticks in different developmental stages and infection status, we concluded that the tick gut microbiota is a self-regulating community of very diverse bacteria contributing to a defined set of metabolic pathways and functions with yet unexplored relevance for tick fitness and/or bacterial community stability. We propose a change of focus in which the tick microbiome must be analyzed in all dimensions, highlighting their functional traits, instead of the conventional taxonomic profiling.

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Dataset Information

Beyond Taxonomic Analysis of Microbiomes: A Functional Approach for Revisiting Microbiome Changes in Colorectal Cancer.

Publications

Beyond Taxonomic Analysis of Microbiomes: A Functional Approach for Revisiting Microbiome Changes in Colorectal Cancer.

Similar Datasets

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