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Navid, Ali

Publications and source records attributed to Navid, Ali.

STREAMS guidelines: standards for technical reporting in environmental and host-associated microbiome studies

The interdisciplinary nature of microbiome research, coupled with the generation of complex multi-omics data, makes knowledge sharing challenging. The Strengthening the Organization and Reporting of Microbiome Studies (STORMS) guidelines provide a checklist for the reporting of study information, experimental design and analytical methods within a scientific manuscript on human microbiome research. Here, in this Consensus Statement, we present the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines. The guidelines expand on STORMS and include 67 items to support the reporting and review of environmental (for example, terrestrial, aquatic, atmospheric and engineered), synthetic and non-human host-associated microbiome studies in a standardized and machine-actionable manner. Based on input from 248 researchers spanning 28 countries, we provide detailed guidance, including comparisons with STORMS, and case studies that demonstrate the usage of the STREAMS guidelines. In conclusion, STREAMS, like STORMS, will be a living community resource updated by the Consortium with consensus-building input of the broader community.

59 BASIC BIOLOGICAL SCIENCES↗

Transporter annotations are holding up progress in metabolic modeling

Mechanistic, constraint-based models of microbial isolates or communities are a staple in the metabolic analysis toolbox, but predictions about microbe-microbe and microbe-environment interactions are only as good as the accuracy of transporter annotations. A number of hurdles stand in the way of comprehensive functional assignments for membrane transporters. These include general or non-specific substrate assignments, ambiguity in the localization, directionality and reversibility of a transporter, and the many-to-many mapping of substrates, transporters and genes. In this perspective, we summarize progress in both experimental and computational approaches used to determine the function of transporters and consider paths forward that integrate both. Investment in accurate, high-throughput functional characterization is needed to train the next-generation of predictive tools toward genome-scale metabolic network reconstructions that better predict phenotypes and interactions. More reliable predictions in this domain will benefit fields ranging from personalized medicine to metabolic engineering to microbial ecology.

Casey, John↗

Multi-scale models of whole cells: progress and challenges

Whole-cell modeling is “the ultimate goal” of computational systems biology and “a grand challenge for 21st century”. These complex, highly detailed models account for the activity of every molecule in a cell and serve as comprehensive knowledgebases for the modeled system. Their scope and utility far surpass those of other systems models. In fact, whole-cell models (WCMs) are an amalgam of several types of “system” models. The models are simulated using a hybrid modeling method where the appropriate mathematical methods for each biological process are used to simulate their behavior. Given the complexity of the models, the process of developing and curating these models is labor-intensive and to date only a handful of these models have been developed. While whole-cell models provide valuable and novel biological insights, and to date have identified some novel biological phenomena, their most important contribution has been to highlight the discrepancy between available data and observations that are used for the parametrization and validation of complex biological models. Another realization has been that current whole-cell modeling simulators are slow and to run models that mimic more complex (e.g., multi-cellular) biosystems, those need to be executed in an accelerated fashion on high-performance computing platforms. In this manuscript, we review the progress of whole-cell modeling to date and discuss some of the ways that they can be improved.

59 BASIC BIOLOGICAL SCIENCES↗

Uses of Multi-Objective Flux Analysis for Optimization of Microbial Production of Secondary Metabolites

Secondary metabolites are not essential for the growth of microorganisms, but they play a critical role in how microbes interact with their surroundings. In addition to this important ecological role, secondary metabolites also have a variety of agricultural, medicinal, and industrial uses, and thus the examination of secondary metabolism of plants and microbes is a growing scientific field. While the chemical production of certain secondary metabolites is possible, industrial-scale microbial production is a green and economically attractive alternative. This is even more true, given the advances in bioengineering that allow us to alter the workings of microbes in order to increase their production of compounds of interest. This type of engineering requires detailed knowledge of the “chassis” organism’s metabolism. Since the resources and the catalytic capacity of enzymes in microbes is finite, it is important to examine the tradeoffs between various bioprocesses in an engineered system and alter its working in a manner that minimally perturbs the robustness of the system while allowing for the maximum production of a product of interest. The in silico multi-objective analysis of metabolism using genome-scale models is an ideal method for such examinations.

59 BASIC BIOLOGICAL SCIENCES↗

Electrogenetic signaling and information propagation for controlling microbial consortia via programmed lysis

To probe signal propagation and genetic actuation in microbial consortia, we have coopted the components of both redox and quorum sensing (QS) signaling into a communication network for guiding composition by “programming” cell lysis. Here, in this paper, we use an electrode to generate hydrogen peroxide as a redox cue that determines consortia composition. The oxidative stress regulon of Escherichia coli, OxyR, is employed to receive and transform this signal into a QS signal that coordinates the lysis of a subpopulation of cells. We examine a suite of information transfer modalities including “monoculture” and “transmitter-receiver” models, as well as a series of genetic circuits that introduce time-delays for altering information relay, thereby expanding design space. A simple mathematical model aids in developing communication schemes that accommodate the transient nature of redox signals and the “collective” attributes of QS signals. We suggest this platform methodology will be useful in understanding and controlling synthetic microbial consortia for a variety of applications, including biomanufacturing and biocontainment.

59 BASIC BIOLOGICAL SCIENCES↗