Dataset Information

Synthesis of multi-omic data and community metabolic models reveals insights into the role of hydrogen sulfide in colon cancer.

ABSTRACT: Multi-omic data and genome-scale microbial metabolic models have allowed us to examine microbial communities, community function, and interactions in ways that were not available to us historically. Now, one of our biggest challenges is determining how to integrate data and maximize data potential. Our study demonstrates one way in which to test a hypothesis by combining multi-omic data and community metabolic models. Specifically, we assess hydrogen sulfide production in colorectal cancer based on stool, mucosa, and tissue samples collected on and off the tumor site within the same individuals. 16S rRNA microbial community and abundance data were used to select and inform the metabolic models. We then used MICOM, an open source platform, to track the metabolic flux of hydrogen sulfide through a defined microbial community that either represented on-tumor or off-tumor sample communities. We also performed targeted and untargeted metabolomics, and used the former to quantitatively evaluate our model predictions. A deeper look at the models identified several unexpected but feasible reactions, microbes, and microbial interactions involved in hydrogen sulfide production for which our 16S and metabolomic data could not account. These results will guide future in vitro, in vivo, and in silico tests to establish why hydrogen sulfide production is increased in tumor tissue.

SUBMITTER: Hale VL

PROVIDER: S-EPMC6191348 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Synthesis of multi-omic data and community metabolic models reveals insights into the role of hydrogen sulfide in colon cancer.

Hale Vanessa L VL Jeraldo Patricio P Mundy Michael M Yao Janet J Keeney Gary G Scott Nancy N Cheek E Heidi EH Davidson Jennifer J Greene Megan M Martinez Christine C Lehman John J Pettry Chandra C Reed Erica E Lyke Kelly K White Bryan A BA Diener Christian C Resendis-Antonio Osbaldo O Gransee Jaime J Dutta Tumpa T Petterson Xuan-Mai XM Boardman Lisa L Larson David D Nelson Heidi H Chia Nicholas N

Methods (San Diego, Calif.) 20180426

Multi-omic data and genome-scale microbial metabolic models have allowed us to examine microbial communities, community function, and interactions in ways that were not available to us historically. Now, one of our biggest challenges is determining how to integrate data and maximize data potential. Our study demonstrates one way in which to test a hypothesis by combining multi-omic data and community metabolic models. Specifically, we assess hydrogen sulfide production in colorectal cancer based ...[more]

PMID: 29704665

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Project description:BackgroundOne goal of multi-omic studies is to identify interpretable predictive models for outcomes of interest, with analytes drawn from multiple omes. Such findings could support refined biological insight and hypothesis generation. However, standard analytical approaches are not designed to be "ome aware." Thus, some researchers analyze data from one ome at a time, and then combine predictions across omes. Others resort to correlation studies, cataloging pairwise relationships, but lacking an obvious approach for cohesive and interpretable summaries of these catalogs.MethodsWe present a novel workflow for building predictive regression models from network neighborhoods in multi-omic networks. First, we generate pairwise regression models across all pairs of analytes from all omes, encoding the resulting "top table" of relationships in a network. Then, we build predictive logistic regression models using the analytes in network neighborhoods of interest. We call this method CANTARE (Consolidated Analysis of Network Topology And Regression Elements).ResultsWe applied CANTARE to previously published data from healthy controls and patients with inflammatory bowel disease (IBD) consisting of three omes: gut microbiome, metabolomics, and microbial-derived enzymes. We identified 8 unique predictive models with AUC > 0.90. The number of predictors in these models ranged from 3 to 13. We compare the results of CANTARE to random forests and elastic-net penalized regressions, analyzing AUC, predictions, and predictors. CANTARE AUC values were competitive with those generated by random forests and penalized regressions. The top 3 CANTARE models had a greater dynamic range of predicted probabilities than did random forests and penalized regressions (p-value = 1.35 × 10-5). CANTARE models were significantly more likely to prioritize predictors from multiple omes than were the alternatives (p-value = 0.005). We also showed that predictive models from a network based on pairwise models with an interaction term for IBD have higher AUC than predictive models built from a correlation network (p-value = 0.016). R scripts and a CANTARE User's Guide are available at https://sourceforge.net/projects/cytomelodics/files/CANTARE/ .ConclusionCANTARE offers a flexible approach for building parsimonious, interpretable multi-omic models. These models yield quantitative and directional effect sizes for predictors and support the generation of hypotheses for follow-up investigation.

Dataset Information

Synthesis of multi-omic data and community metabolic models reveals insights into the role of hydrogen sulfide in colon cancer.

Publications

Synthesis of multi-omic data and community metabolic models reveals insights into the role of hydrogen sulfide in colon cancer.

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