More Like this

1. Learning from the unknown: exploring the range of bacterial functionality

   https://doi.org/10.1093/nar/gkad757  

   Mahlich, Yannick; Zhu, Chengsheng; Chung, Henri; Velaga, Pavan K.; De Paolis Kaluza, M. Clara; Radivojac, Predrag; Friedberg, Iddo; Bromberg, Yana (September 2023, Nucleic Acids Research)

   Abstract Determining the repertoire of a microbe's molecular functions is a central question in microbial biology. Modern techniques achieve this goal by comparing microbial genetic material against reference databases of functionally annotated genes/proteins or known taxonomic markers such as 16S rRNA. Here, we describe a novel approach to exploring bacterial functional repertoires without reference databases. Our Fusion scheme establishes functional relationships between bacteria and assigns organisms to Fusion-taxa that differ from otherwise defined taxonomic clades. Three key findings of our work stand out. First, bacterial functional comparisons outperform marker genes in assigning taxonomic clades. Fusion profiles are also better for this task than other functional annotation schemes. Second, Fusion-taxa are robust to addition of novel organisms and are, arguably, able to capture the environment-driven bacterial diversity. Finally, our alignment-free nucleic acid-based Siamese Neural Network model, created using Fusion functions, enables finding shared functionality of very distant, possibly structurally different, microbial homologs. Our work can thus help annotate functional repertoires of bacterial organisms and further guide our understanding of microbial communities. 

   more » « less
2. Salinity Impacts the Functional mcrA and dsrA Gene Abundances in Everglades Marshes

   https://doi.org/10.3390/microorganisms11051180  

   Jordan, Deidra S.; Kominoski, John; Servais, Shelby; Mills, DeEtta (May 2023, Microorganisms)

   Coastal wetlands, such as the Everglades, are increasingly being exposed to stressors that have the potential to modify their existing ecological processes because of global climate change. Their soil microbiomes include a population of organisms important for biogeochemical cycling, but continual stresses can disturb the community’s composition, causing functional changes. The Everglades feature wetlands with varied salinity levels, implying that they contain microbial communities with a variety of salt tolerances and microbial functions. Therefore, tracking the effects of stresses on these populations in freshwater and brackish marshes is critical. The study addressed this by utilizing next generation sequencing (NGS) to construct a baseline soil microbial community. The carbon and sulfur cycles were studied by sequencing a microbial functional gene involved in each process, the mcrA and dsrA functional genes, respectively. Saline was introduced over two years to observe the taxonomic alterations that occurred after a long-term disturbance such as seawater intrusion. It was observed that saltwater dosing increased sulfite reduction in freshwater peat soils and decreased methylotrophy in brackish peat soils. These findings add to the understanding of microbiomes by demonstrating how changes in soil qualities impact communities both before and after a disturbance such as saltwater intrusion. 

   more » « less
3. Immune-Microbiota Crosstalk Underlying Inflammatory Bowel Disease

   https://doi.org/10.1007/978-3-030-91415-8_2  

   Xu, Congmin; Mac, Quoc D.; Jia, Qiong; Qiu, Peng (November 2021, In: Wei, Y., Li, M., Skums, P., Cai, Z. (eds) Bioinformatics Research and Applications. ISBRA 2021. Lecture Notes in Computer Science)

   Wei, Yanjie; Li, Min; Skums, Pavel; Cai, Zhipeng (Ed.)

   Long-time evolution has shaped a harmonious host-microbiota symbiosis consisting of intestinal microbiota in conjunction with the host immune system. Inflammatory bowel disease (IBD) is a result of the dysbiotic microbial composition together with aberrant mucosal immune responses, while the underlying mechanism is far from clear. In this report, we creatively proposed that when correlating with the host metabolism, functional microbial communities matter more than individual bacteria. Based on this assumption, we performed a systematic analysis to characterize the co-metabolism of host and gut microbiota established on a set of newly diagnosed Crohn’s disease (CD) samples and healthy controls. From the host side, we applied gene set enrichment analysis on host mucosal proteome data to identify those host pathways associated with CD. At the same time, we applied community detection analysis on the metagenomic data of mucosal microbiota to identify those microbial communities, which were assembled for a functional purpose. Then, the correlation analysis between host pathways and microbial communities was conducted. We discovered two microbial communities negatively correlated with IBD enriched host pathways. The dominant genera for these two microbial communities are known as health-benefits and could serve as a reference for designing complex beneficial microorganisms for IBD treatment. The correlated host pathways are all relevant to MHC antigen presentation pathways, which hints toward a possible mechanism of immune-microbiota cross talk underlying IBD. 

   more » « less
4. Linking plasmid-based beta-lactamases to their bacterial hosts using single-cell fusion PCR

   https://doi.org/10.7554/eLife.66834  

   Diebold, Peter J; New, Felicia N; Hovan, Michael; Satlin, Michael J; Brito, Ilana L (July 2021, eLife)

   null (Ed.)

   The horizonal transfer of plasmid-encoded genes allows bacteria to adapt to constantly shifting environmental pressures, bestowing functional advantages to their bacterial hosts such as antibiotic resistance, metal resistance, virulence factors, and polysaccharide utilization. However, common molecular methods such as short- and long-read sequencing of microbiomes cannot associate extrachromosomal plasmids with the genome of the host bacterium. Alternative methods to link plasmids to host bacteria are either laborious, expensive, or prone to contamination. Here we present the One-step Isolation and Lysis PCR (OIL-PCR) method, which molecularly links plasmid-encoded genes with the bacterial 16S rRNA gene via fusion PCR performed within an emulsion. After validating this method, we apply it to identify the bacterial hosts of three clinically relevant beta-lactamases within the gut microbiomes of neutropenic patients, as they are particularly vulnerable multidrug-resistant infections. We successfully detect the known association of a multi-drug resistant plasmid with Klebsiella pneumoniae , as well as the novel associations of two low-abundance genera, Romboutsia and Agathobacter . Further investigation with OIL-PCR confirmed that our detection of Romboutsia is due to its physical association with Klebsiella as opposed to directly harboring the beta-lactamase genes. Here we put forth a robust, accessible, and high-throughput platform for sensitively surveying the bacterial hosts of mobile genes, as well as detecting physical bacterial associations such as those occurring within biofilms and complex microbial communities. 

   more » « less
5. Optimizing state change detection in functional temporal networks through dynamic community detection

   https://doi.org/10.1093/comnet/cny030  

   Vaiana, Michael; Goldberg, Ethan M.; Muldoon, Sarah F.; Porter, ed., Mason (December 2018, Journal of Complex Networks)

   Abstract Dynamic community detection provides a coherent description of network clusters over time, allowing one to track the growth and death of communities as the network evolves. However, modularity maximization, a popular method for performing multilayer community detection, requires the specification of an appropriate null network as well as resolution and interlayer coupling parameters. Importantly, the ability of the algorithm to accurately detect community evolution is dependent on the choice of these parameters. In functional temporal networks, where evolving communities reflect changing functional relationships between network nodes, it is especially important that the detected communities reflect any state changes of the system. Here, we present analytical work suggesting that a uniform null network provides improved sensitivity to the detection of small evolving communities in temporal networks with positive edge weights bounded above by 1, such as certain types of correlation networks. We then propose a method for increasing the sensitivity of modularity maximization to state changes in nodal dynamics by modelling self-identity links between layers based on the self-similarity of the network nodes between layers. This method is more appropriate for functional temporal networks from both a modelling and mathematical perspective, as it incorporates the dynamic nature of network nodes. We motivate our method based on applications in neuroscience where network nodes represent neurons and functional edges represent similarity of firing patterns in time. We show that in simulated data sets of neuronal spike trains, updating interlayer links based on the firing properties of the neurons provides superior community detection of evolving network structure when groups of neurons change their firing properties over time. Finally, we apply our method to experimental calcium imaging data that monitors the spiking activity of hundreds of neurons to track the evolution of neuronal communities during a state change from the awake to anaesthetized state. 

   more » « less