Genetic Co-Occurrence Network across Sequenced Microbes

The phenotype of any organism on earth is, in large part, the consequence of interplay between numerous gene products encoded in the genome, and such interplay between gene products affects the evolutionary fate of the genome itself through the resulting phenotype. In this regard, contemporary genomes can be used as molecular records that reveal associations of various genes working in their natural lifestyles. By analyzing thousands of orthologs across ~600 bacterial species, we constructed a map of gene-gene co-occurrence across much of the sequenced biome. If genes preferentially co-occur in the same organisms, they were called herein correlogs; in the opposite case, called anti-correlogs. To quantify correlogy and anti-correlogy, we alleviated the contribution of indirect correlations between genes by adapting ideas developed for reverse engineering of transcriptional regulatory networks. Resultant correlogous associations are highly enriched for physically interacting proteins and for co-expressed transcripts, clearly differentiating a subgroup of functionally-obligatory protein interactions from conditional or transient interactions. Other biochemical and phylogenetic properties were also found to be reflected in correlogous and anti-correlogous relationships. Additionally, our study elucidates the global organization of the gene association map, in which various modules of correlogous genes are strikingly interconnected by anti-correlogous crosstalk between the modules. We then demonstrate the effectiveness of such associations along different domains of life and environmental microbial communities. These phylogenetic profiling approaches infer functional coupling of genes regardless of mechanistic details, and may be useful to guide exogenous gene import in synthetic biology.Comment: Supporting information is available at PLoS Computational Biolog

The fecal resistome of dairy cattle is associated with diet during nursing.

Antimicrobial resistance is a global public health concern, and livestock play a significant role in selecting for resistance and maintaining such reservoirs. Here we study the succession of dairy cattle resistome during early life using metagenomic sequencing, as well as the relationship between resistome, gut microbiota, and diet. In our dataset, the gut of dairy calves serves as a reservoir of 329 antimicrobial resistance genes (ARGs) presumably conferring resistance to 17 classes of antibiotics, and the abundance of ARGs declines gradually during nursing. ARGs appear to co-occur with antibacterial biocide or metal resistance genes. Colostrum is a potential source of ARGs observed in calves at day 2. The dynamic changes in the resistome are likely a result of gut microbiota assembly, which is closely associated with diet transition in dairy calves. Modifications in the resistome may be possible via early-life dietary interventions to reduce overall antimicrobial resistance

Metabolic network percolation quantifies biosynthetic capabilities across the human oral microbiome

The biosynthetic capabilities of microbes underlie their growth and interactions, playing a prominent role in microbial community structure. For large, diverse microbial communities, prediction of these capabilities is limited by uncertainty about metabolic functions and environmental conditions. To address this challenge, we propose a probabilistic method, inspired by percolation theory, to computationally quantify how robustly a genome-derived metabolic network produces a given set of metabolites under an ensemble of variable environments. We used this method to compile an atlas of predicted biosynthetic capabilities for 97 metabolites across 456 human oral microbes. This atlas captures taxonomically-related trends in biomass composition, and makes it possible to estimate inter-microbial metabolic distances that correlate with microbial co-occurrences. We also found a distinct cluster of fastidious/uncultivated taxa, including several Saccharibacteria (TM7) species, characterized by their abundant metabolic deficiencies. By embracing uncertainty, our approach can be broadly applied to understanding metabolic interactions in complex microbial ecosystems.T32GM008764 - NIGMS NIH HHS; T32 GM008764 - NIGMS NIH HHS; R01 DE024468 - NIDCR NIH HHS; R01 GM121950 - NIGMS NIH HHS; DE-SC0012627 - Biological and Environmental Research; RGP0020/2016 - Human Frontier Science Program; NSFOCE-BSF 1635070 - National Science Foundation; HR0011-15-C-0091 - Defense Advanced Research Projects Agency; R37DE016937 - NIDCR NIH HHS; R37 DE016937 - NIDCR NIH HHS; R01GM121950 - NIGMS NIH HHS; R01DE024468 - NIDCR NIH HHS; 1457695 - National Science FoundationPublished versio

Soil Microbial Networks Shift Across a High-Elevation Successional Gradient.

While it is well established that microbial composition and diversity shift along environmental gradients, how interactions among microbes change is poorly understood. Here, we tested how community structure and species interactions among diverse groups of soil microbes (bacteria, fungi, non-fungal eukaryotes) change across a fundamental ecological gradient, succession. Our study system is a high-elevation alpine ecosystem that exhibits variability in successional stage due to topography and harsh environmental conditions. We used hierarchical Bayesian joint distribution modeling to remove the influence of environmental covariates on species distributions and generated interaction networks using the residual species-to-species variance-covariance matrix. We hypothesized that as ecological succession proceeds, diversity will increase, species composition will change, and soil microbial networks will become more complex. As expected, we found that diversity of most taxonomic groups increased over succession, and species composition changed considerably. Interestingly, and contrary to our hypothesis, interaction networks became less complex over succession (fewer interactions per taxon). Interactions between photosynthetic microbes and any other organism became less frequent over the gradient, whereas interactions between plants or soil microfauna and any other organism were more abundant in late succession. Results demonstrate that patterns in diversity and composition do not necessarily relate to patterns in network complexity and suggest that network analyses provide new insight into the ecology of highly diverse, microscopic communities

The Gut Microbiota of Bali among the World Populations: Connecting Diet, Urbanisation, and Obesity.

Community assembly of the gut microbiota is believed to be achieved through an interaction between the host’s lifestyle and genetic. Failure to address these population-specific factors may lead to unsuccessful detection of obesity patterns in the human gut microbiota. This thesis aimed to extricate lifestyle and genotypic patterns from the human gut microbiota, and to identify obesity patterns in the microbiota of a population with defined lifestyle and ethnogeography. This study utilized the unique cultural and ethnogeography characteristics of Bali people. In the first part of this thesis, the faecal microbiota of 36 ethnic Balinese individuals was compared by obesity, diet patterns (through food frequency questionnaire), and genetic lineage (through mitochondrial DNA [mtDNA] haplotyping). Subjects with non-R mtDNA haplogroup were found to have a higher prevalence of Prevotella-dominated enterotype and higher risk of developing obesity. Moreover, the enterotypes were found to be linked to long-term diet patterns, particularly to choices of staple foods in meals. In the second part of this thesis, the microbiota of 41 Bali individuals was contrasted with the microbiota of 283 other people from 7 ethnogeographically distinct rural and urban populations. Principal Coordinate Analyses of the unweighted Unifrac distance placed Bali individuals between the rural and urban samples, reflecting Bali’s status as a newly-industrialised society. Urbanisation is also associated with the abundance of Prevotella and Bacteroides across populations, but not obesity. Collectively, these findings highlighted that perpetuating host factors (lifestyle, genotype) are drivers of microbial community assembly in the human gut. Importantly, this thesis showed that understanding the genetic and socio-cultural context of a population could be the key to effective identification of microbial biomarkers in obesity

Strong associations between microbe phenotypes and their network architecture

Understanding the dependence and interplay between architecture and function in biological networks has great relevance to disease progression, biological fabrication and biological systems in general. We propose methods to assess the association of various microbe characteristics and phenotypes with the topology of their networks. We adopt an automated approach to characterize metabolic networks of 32 microbial species using 11 topological metrics from complex networks. Clustering allows us to extract the indispensable, independent and informative metrics. Using hierarchical linear modeling, we identify relevant subgroups of these metrics and establish that they associate with microbial phenotypes surprisingly well. This work can serve as a stepping stone to cataloging biologically relevant topological properties of networks and towards better modeling of phenotypes. The methods we use can also be applied to networks from other disciplines.Comment: Replaced by the version scheduled to appear in Phys. Rev. E (Rapid Comm.

Evidence of global-scale aeolian dispersal and endemism in isolated geothermal microbial communities of Antarctica

New evidence in aerobiology challenges the assumption that geographical isolation is an effective barrier to microbial transport. However, given the uncertainty with which aerobiological organisms are recruited into existing communities, the ultimate impact of microbial dispersal is difficult to assess. To evaluate the ecological significance of global-scale microbial dispersal, molecular genetic approaches were used to examine microbial communities inhabiting fumarolic soils on Mt. Erebus, the southernmost geothermal site on Earth. There, hot, fumarolic soils provide an effective environmental filter to test the viability of organisms that have been distributed via aeolian transport over geological time. We find that cosmopolitan thermophiles dominate the surface, whereas endemic Archaea and members of poorly understood Bacterial candidate divisions dominate the immediate subsurface. These results imply that aeolian processes readily disperse viable organisms globally, where they are incorporated into pre-existing complex communities of endemic and cosmopolitan taxa