Inferring directional relationships in microbial communities using signed Bayesian networks

Background Microbe-microbe and host-microbe interactions in a microbiome play a vital role in both health and disease. However, the structure of the microbial community and the colonization patterns are highly complex to infer even under controlled wet laboratory conditions. In this study, we investigate what information, if any, can be provided by a Bayesian Network (BN) about a microbial community. Unlike the previously proposed Co-occurrence Networks (CoNs), BNs are based on conditional dependencies and can help in revealing complex associations. Results In this paper, we propose a way of combining a BN and a CoN to construct a signed Bayesian Network (sBN). We report a surprising association between directed edges in signed BNs and known colonization orders. Conclusions BNs are powerful tools for community analysis and extracting influences and colonization patterns, even though the analysis only uses an abundance matrix with no temporal information. We conclude that directed edges in sBNs when combined with negative correlations are consistent with and strongly suggestive of colonization order.

[1]  William D. Shannon,et al.  Patterned progression of bacterial populations in the premature infant gut , 2014, Proceedings of the National Academy of Sciences.

[2]  Giri Narasimhan,et al.  Dynamic interaction network inference from longitudinal microbiome data , 2018 .

[3]  Scott T. Weiss,et al.  Longitudinal Prediction of the Infant Gut Microbiome with Dynamic Bayesian Networks , 2016, Scientific Reports.

[4]  M A Krohn,et al.  Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation , 1991, Journal of clinical microbiology.

[5]  Hong Gu,et al.  BiomeNet: A Bayesian Model for Inference of Metabolic Divergence among Microbial Communities , 2014, PLoS Comput. Biol..

[6]  Diego Colombo,et al.  Order-independent constraint-based causal structure learning , 2012, J. Mach. Learn. Res..

[7]  Joshua B. Tenenbaum,et al.  Inferring causal networks from observations and interventions , 2003, Cogn. Sci..

[8]  Deborah A. Hogan,et al.  Medically important bacterial–fungal interactions , 2010, Nature Reviews Microbiology.

[9]  Nir Friedman,et al.  Probabilistic Graphical Models - Principles and Techniques , 2009 .

[10]  Tommi S. Jaakkola,et al.  Continuous Representations of Time-Series Gene Expression Data , 2003, J. Comput. Biol..

[11]  Thomas S. Richardson,et al.  Learning high-dimensional directed acyclic graphs with latent and selection variables , 2011, 1104.5617.

[12]  N. Cerca,et al.  Influence of Biofilm Formation by Gardnerella vaginalis and Other Anaerobes on Bacterial Vaginosis. , 2015, The Journal of infectious diseases.

[13]  Jing Yu,et al.  Computational Inference of Neural Information Flow Networks , 2006, PLoS Comput. Biol..

[14]  Hong Yan,et al.  Incorporating prior information into differential network analysis using non‐paranormal graphical models , 2017, Bioinform..

[15]  Jean-Baptiste Denis,et al.  Bayesian Networks , 2014 .

[16]  D. Grenier,et al.  The oral cavity as a reservoir of bacterial pathogens for focal infections. , 2000, Microbes and infection.

[17]  Thomas H. Scheike,et al.  Coordinate Descent Methods for the Penalized Semiparametric Additive Hazards Model , 2012 .

[18]  Marco Scutari,et al.  Bayesian Network Constraint-Based Structure Learning Algorithms: Parallel and Optimised Implementations in the bnlearn R Package , 2014, ArXiv.

[19]  Nicholas J. Cox,et al.  Speaking Stata: Correlation with Confidence, or Fisher's z revisited , 2008 .

[20]  Claus Dethlefsen,et al.  deal: A Package for Learning Bayesian Networks , 2003 .

[21]  Nir Friedman,et al.  Data Analysis with Bayesian Networks: A Bootstrap Approach , 1999, UAI.

[22]  Erliang Zeng,et al.  Microbiome Analysis: State of the Art and Future Trends , 2016 .

[23]  Blair J. Rossetti,et al.  Biogeography of a human oral microbiome at the micron scale , 2016, Proceedings of the National Academy of Sciences.

[24]  Elizabeth A. Grice,et al.  The skin microbiome , 2020, Nature.

[25]  Giri Narasimhan,et al.  Inferring Relationships in Microbiomes from Signed Bayesian Networks , 2018, 2018 IEEE 8th International Conference on Computational Advances in Bio and Medical Sciences (ICCABS).

[26]  S. Lebeer,et al.  Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health , 2015, Front. Physiol..

[27]  B. Efron,et al.  Bootstrap confidence levels for phylogenetic trees. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Bartek Wilczynski,et al.  BNFinder: exact and efficient method for learning Bayesian networks , 2008, Bioinform..

[29]  Xuan Vinh Nguyen,et al.  GlobalMIT: learning globally optimal dynamic bayesian network with the mutual information test criterion , 2011, Bioinform..

[30]  C. Zenobia,et al.  The relationship of the oral microbiotia to periodontal health and disease. , 2011, Cell host & microbe.

[31]  Curtis Huttenhower,et al.  Microbial Co-occurrence Relationships in the Human Microbiome , 2012, PLoS Comput. Biol..

[32]  M. Campos,et al.  Microbial "social networks" , 2015, BMC Genomics.

[33]  Y. Sanz,et al.  Imbalance in the composition of the duodenal microbiota of children with coeliac disease. , 2007, Journal of medical microbiology.

[34]  Ivo Grosse,et al.  Comparison of the oral microbiome of patients with generalized aggressive periodontitis and periodontitis-free subjects. , 2019, Archives of oral biology.

[35]  M. Kilian,et al.  Microbiology of the early colonization of human enamel and root surfaces in vivo. , 1987, Scandinavian journal of dental research.

[36]  R. Fichorova,et al.  The Human Microbiome during Bacterial Vaginosis , 2016, Clinical Microbiology Reviews.

[37]  J. D. de Winter Using the Student ’ s t-test with extremely small sample sizes , 2013 .

[38]  Scott T. Weiss,et al.  CGBayesNets: Conditional Gaussian Bayesian Network Learning and Inference with Mixed Discrete and Continuous Data , 2014, PLoS Comput. Biol..

[39]  Judea Pearl,et al.  Probabilistic reasoning in intelligent systems - networks of plausible inference , 1991, Morgan Kaufmann series in representation and reasoning.

[40]  Michal Linial,et al.  Using Bayesian Networks to Analyze Expression Data , 2000, J. Comput. Biol..

[41]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[42]  Peter Bühlmann,et al.  Causal Inference Using Graphical Models with the R Package pcalg , 2012 .

[43]  Robert J. Palmer,et al.  Communication among Oral Bacteria , 2002, Microbiology and Molecular Biology Reviews.

[44]  Lu Wang,et al.  The NIH Human Microbiome Project. , 2009, Genome research.

[45]  Tom Burr,et al.  Causation, Prediction, and Search , 2003, Technometrics.

[46]  H. Darmani Todar's Online Textbook of Bacteriology , 2006 .

[47]  Pearl D Houghteling,et al.  Why Is Initial Bacterial Colonization of the Intestine Important to Infants' and Children's Health? , 2015, Journal of pediatric gastroenterology and nutrition.

[48]  B. Efron,et al.  Bootstrap confidence levels for phylogenetic trees. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[49]  Yeisoo Yu,et al.  Uncovering the novel characteristics of Asian honey bee, Apis cerana, by whole genome sequencing , 2015, BMC Genomics.

[50]  P. Kolenbrander,et al.  Adhere today, here tomorrow: oral bacterial adherence , 1993, Journal of bacteriology.

[51]  Judea Pearl,et al.  Equivalence and Synthesis of Causal Models , 1990, UAI.

[52]  R. Knight,et al.  Bacterial Community Variation in Human Body Habitats Across Space and Time , 2009, Science.

[53]  Marco Scutari,et al.  Learning Bayesian Networks with the bnlearn R Package , 2009, 0908.3817.

[54]  Martin Hartmann,et al.  Introducing mothur: Open-Source, Platform-Independent, Community-Supported Software for Describing and Comparing Microbial Communities , 2009, Applied and Environmental Microbiology.

[55]  Katherine H. Huang,et al.  Structure, Function and Diversity of the Healthy Human Microbiome , 2012, Nature.

[56]  Julia Oh,et al.  Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis , 2012, Genome research.

[57]  Zaid Abdo,et al.  Temporal Dynamics of the Human Vaginal Microbiota , 2012, Science Translational Medicine.