Deciphering microbial interactions and detecting keystone species with co-occurrence networks

Co-occurrence networks produced from microbial survey sequencing data are frequently used to identify interactions between community members. While this approach has potential to reveal ecological processes, it has been insufficiently validated due to the technical limitations inherent in studying complex microbial ecosystems. Here, we simulate multi-species microbial communities with known interaction patterns using generalized Lotka-Volterra dynamics. We then construct co-occurrence networks and evaluate how well networks reveal the underlying interactions and how experimental and ecological parameters can affect network inference and interpretation. We find that co-occurrence networks can recapitulate interaction networks under certain conditions, but that they lose interpretability when the effects of habitat filtering become significant. We demonstrate that networks suffer from local hot spots of spurious correlation in the neighborhood of hub species that engage in many interactions. We also identify topological features associated with keystone species in co-occurrence networks. This study provides a substantiated framework to guide environmental microbiologists in the construction and interpretation of co-occurrence networks from microbial survey datasets.

[1]  C. Fuqua,et al.  Bacterial competition: surviving and thriving in the microbial jungle , 2010, Nature Reviews Microbiology.

[2]  E. Stackebrandt,et al.  Effect of genome size and rrn gene copy number on PCR amplification of 16S rRNA genes from a mixture of bacterial species , 1995, Applied and environmental microbiology.

[3]  R. Daniel,et al.  Phylogenetic Diversity and Metabolic Potential Revealed in a Glacier Ice Metagenome , 2009, Applied and Environmental Microbiology.

[4]  Alan M. Frieze,et al.  Random graphs , 2006, SODA '06.

[5]  J. Diamond,et al.  Ecology and Evolution of Communities , 1976, Nature.

[6]  Duncan J. Watts,et al.  Collective dynamics of ‘small-world’ networks , 1998, Nature.

[7]  J. Raes,et al.  Microbial interactions: from networks to models , 2012, Nature Reviews Microbiology.

[8]  T. Urich,et al.  Longitudinal study of murine microbiota activity and interactions with the host during acute inflammation and recovery , 2014, The ISME Journal.

[9]  Serguei Saavedra,et al.  Strong contributors to network persistence are the most vulnerable to extinction , 2011, Nature.

[10]  Gunnar Rätsch,et al.  Ecological Modeling from Time-Series Inference: Insight into Dynamics and Stability of Intestinal Microbiota , 2013, PLoS Comput. Biol..

[11]  K. Foster,et al.  Competition, Not Cooperation, Dominates Interactions among Culturable Microbial Species , 2012, Current Biology.

[12]  Christine Wiedinmyer,et al.  Characterization of Airborne Microbial Communities at a High-Elevation Site and Their Potential To Act as Atmospheric Ice Nuclei , 2009, Applied and Environmental Microbiology.

[13]  Daniel Segrè,et al.  Environments that Induce Synthetic Microbial Ecosystems , 2010, PLoS Comput. Biol..

[14]  J. Faith,et al.  Predicting a Human Gut Microbiota’s Response to Diet in Gnotobiotic Mice , 2011, Science.

[15]  Martin F. Polz,et al.  Bias in Template-to-Product Ratios in Multitemplate PCR , 1998, Applied and Environmental Microbiology.

[16]  Didier L. Baho,et al.  Fundamentals of Microbial Community Resistance and Resilience , 2012, Front. Microbio..

[17]  R. Solé,et al.  Ecological networks and their fragility , 2006, Nature.

[18]  Gábor Csárdi,et al.  The igraph software package for complex network research , 2006 .

[19]  Jonathan Friedman,et al.  Inferring Correlation Networks from Genomic Survey Data , 2012, PLoS Comput. Biol..

[20]  R. Arditi,et al.  Microbial Interactions within a Cheese Microbial Community , 2007, Applied and Environmental Microbiology.

[21]  M. Wagner,et al.  A ‘rare biosphere’ microorganism contributes to sulfate reduction in a peatland , 2010, The ISME Journal.

[22]  Mark D. McDonnell,et al.  Methods for Generating Complex Networks with Selected Structural Properties for Simulations: A Review and Tutorial for Neuroscientists , 2011, Front. Comput. Neurosci..

[23]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[24]  Karline Soetaert,et al.  Solving Differential Equations in R: Package deSolve , 2010 .

[25]  Colin Fontaine,et al.  Stability of Ecological Communities and the Architecture of Mutualistic and Trophic Networks , 2010, Science.

[26]  N. Fierer,et al.  The generation and maintenance of diversity in microbial communities. , 2011, American journal of botany.

[27]  V. Eguíluz,et al.  Highly clustered scale-free networks. , 2001, Physical review. E, Statistical, nonlinear, and soft matter physics.

[28]  Albert,et al.  Emergence of scaling in random networks , 1999, Science.

[29]  Daniel Falush,et al.  Sex and virulence in Escherichia coli: an evolutionary perspective , 2006, Molecular microbiology.

[30]  W. Wanek,et al.  Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing , 2013, Proceedings of the National Academy of Sciences.

[31]  Mehrdad Hajibabaei,et al.  Next‐generation sequencing technologies for environmental DNA research , 2012, Molecular ecology.

[32]  W. Sloan,et al.  Prokaryotic diversity and its limits: microbial community structure in nature and implications for microbial ecology. , 2004, Current opinion in microbiology.

[33]  J. Banfield,et al.  Community structure and metabolism through reconstruction of microbial genomes from the environment , 2004, Nature.

[34]  L. Forney,et al.  The tragedy of the uncommon: understanding limitations in the analysis of microbial diversity , 2008, The ISME Journal.

[35]  H. Flint,et al.  Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon , 2012, The ISME Journal.

[36]  Noah Fierer,et al.  Using network analysis to explore co-occurrence patterns in soil microbial communities , 2011, The ISME Journal.

[37]  William A. Walters,et al.  Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample , 2010, Proceedings of the National Academy of Sciences.

[38]  Roded Sharan,et al.  Competitive and cooperative metabolic interactions in bacterial communities. , 2011, Nature communications.

[39]  Nicholas J. Gotelli,et al.  SPECIES CO‐OCCURRENCE: A META‐ANALYSIS OF J. M. DIAMOND'S ASSEMBLY RULES MODEL , 2002 .

[40]  S. Tringe,et al.  Comparative Metagenomics of Microbial Communities , 2004, Science.

[41]  Charles Ashbacher,et al.  An Illustrated Guide to Theoretical Ecology , 2003 .

[42]  N. Zhou,et al.  Intragenomic Heterogeneity of 16S rRNA Genes Causes Overestimation of Prokaryotic Diversity , 2013, Applied and Environmental Microbiology.

[43]  Christophe Caron,et al.  Towards the human intestinal microbiota phylogenetic core. , 2009, Environmental microbiology.

[44]  Alexandros Stamatakis,et al.  Metagenomic species profiling using universal phylogenetic marker genes , 2013, Nature Methods.

[45]  Debojyoti Dutta,et al.  Local similarity analysis reveals unique associations among marine bacterioplankton species and environmental factors , 2006, Bioinform..

[46]  Lewi Stone,et al.  Competitive exclusion, or species aggregation? , 1992, Oecologia.

[47]  Fabian J. Theis,et al.  Gaussian graphical modeling reconstructs pathway reactions from high-throughput metabolomics data , 2011, BMC Systems Biology.

[48]  Jillian F Banfield,et al.  Microbial communities in acid mine drainage. , 2003, FEMS microbiology ecology.

[49]  J. Wimpenny,et al.  A unifying hypothesis for the structure of microbial biofilms based on cellular automaton models , 1997 .

[50]  B. Stecher,et al.  Colonization resistance and microbial ecophysiology: using gnotobiotic mouse models and single-cell technology to explore the intestinal jungle. , 2013, FEMS microbiology reviews.

[51]  S. Acinas,et al.  Divergence and Redundancy of 16S rRNA Sequences in Genomes with Multiple rrn Operons , 2004, Journal of bacteriology.

[52]  Stefan Bertilsson,et al.  Coherent dynamics and association networks among lake bacterioplankton taxa , 2011, The ISME Journal.

[53]  R. Knight,et al.  Quantitative and Qualitative β Diversity Measures Lead to Different Insights into Factors That Structure Microbial Communities , 2007, Applied and Environmental Microbiology.

[54]  Susan M. Huse,et al.  Microbial Population Structures in the Deep Marine Biosphere , 2007, Science.

[55]  L. Raskin,et al.  Diversity and dynamics of microbial communities in engineered environments and their implications for process stability. , 2003, Current opinion in biotechnology.

[56]  Peter Salamon,et al.  Viral and microbial community dynamics in four aquatic environments , 2010, The ISME Journal.

[57]  J. Castilla,et al.  Challenges in the Quest for Keystones , 1996 .

[58]  L. Roesch,et al.  Low sequencing efforts bias analyses of shared taxa in microbial communities , 2012, Folia Microbiologica.

[59]  Knut Rudi,et al.  Web of ecological interactions in an experimental gut microbiota. , 2010, Environmental microbiology.

[60]  F. Brockman,et al.  Effect of PCR template concentration on the composition and distribution of total community 16S rDNA clone libraries , 1997, Molecular ecology.

[61]  M. Wagner,et al.  Barcoded Primers Used in Multiplex Amplicon Pyrosequencing Bias Amplification , 2011, Applied and Environmental Microbiology.

[62]  G. Pusch,et al.  Phylogenetic conservatism of functional traits in microorganisms , 2012, The ISME Journal.

[63]  A. Klindworth,et al.  Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies , 2012, Nucleic acids research.

[64]  Susan M. Huse,et al.  Global Patterns of Bacterial Beta-Diversity in Seafloor and Seawater Ecosystems , 2011, PloS one.