2,402 research outputs found
Metabolic Model-based Ecological Modeling for Probiotic Design
The microbial community composition in the human gut has a profound effect on
human health. This observation has lead to extensive use of microbiome
therapies, including over-the-counter ``probiotic" treatments intended to alter
the composition of the microbiome. Despite so much promise and commercial
interest, the factors that contribute to the success or failure of
microbiome-targeted treatments remain unclear. We investigate the biotic
interactions that lead to successful engraftment of a novel bacterial strain
introduced to the microbiome as in probiotic treatments. We use pairwise
genome-scale metabolic modeling with a generalized resource allocation
constraint to build a network of interactions between 818 species with well
developed models available in the AGORA database. We create induced sub-graphs
using the taxa present in samples from three experimental engraftment studies
and assess the likelihood of invader engraftment based on network structure. To
do so, we use a set of dynamical models designed to reflect connect network
topology to growth dynamics. We show that a generalized Lotka-Volterra model
has strong ability to predict if a particular invader or probiotic will
successfully engraft into an individual's microbiome. Furthermore, we show that
the mechanistic nature of the model is useful for revealing which
microbe-microbe interactions potentially drive engraftment.Comment: 18 pages, 6 figure
Minimizing the number of optimizations for efficient community dynamic flux balance analysis
Dynamic flux balance analysis uses a quasi-steady state assumption to
calculate an organism's metabolic activity at each time-step of a dynamic
simulation, using the well-known technique of flux balance analysis. For
microbial communities, this calculation is especially costly and involves
solving a linear constrained optimization problem for each member of the
community at each time step. However, this is unnecessary and inefficient, as
prior solutions can be used to inform future time steps. Here, we show that a
basis for the space of internal fluxes can be chosen for each microbe in a
community and this basis can be used to simulate forward by solving a
relatively inexpensive system of linear equations at most time steps. We can
use this solution as long as the resulting metabolic activity remains within
the optimization problem's constraints (i.e. the solution to the linear system
of equations remains a feasible to the linear program). As the solution becomes
infeasible, it first becomes a feasible but degenerate solution to the
optimization problem, and we can solve a different but related optimization
problem to choose an appropriate basis to continue forward simulation. We
demonstrate the efficiency and robustness of our method by comparing with
currently used methods on a four species community, and show that our method
requires at least fewer optimizations to be solved. For reproducibility,
we prototyped the method using Python. Source code is available at
\verb|https://github.com/jdbrunner/surfin_fba|.Comment: 9 figure
Evolution of DNA Replication Protein Complexes in Eukaryotes and Archaea
BACKGROUND: The replication of DNA in Archaea and eukaryotes requires several ancillary complexes, including proliferating cell nuclear antigen (PCNA), replication factor C (RFC), and the minichromosome maintenance (MCM) complex. Bacterial DNA replication utilizes comparable proteins, but these are distantly related phylogenetically to their archaeal and eukaryotic counterparts at best. METHODOLOGY/PRINCIPAL FINDINGS: While the structures of each of the complexes do not differ significantly between the archaeal and eukaryotic versions thereof, the evolutionary dynamic in the two cases does. The number of subunits in each complex is constant across all taxa. However, they vary subtly with regard to composition. In some taxa the subunits are all identical in sequence, while in others some are homologous rather than identical. In the case of eukaryotes, there is no phylogenetic variation in the makeup of each complex-all appear to derive from a common eukaryotic ancestor. This is not the case in Archaea, where the relationship between the subunits within each complex varies taxon-to-taxon. We have performed a detailed phylogenetic analysis of these relationships in order to better understand the gene duplications and divergences that gave rise to the homologous subunits in Archaea. CONCLUSION/SIGNIFICANCE: This domain level difference in evolution suggests that different forces have driven the evolution of DNA replication proteins in each of these two domains. In addition, the phylogenies of all three gene families support the distinctiveness of the proposed archaeal phylum Thaumarchaeota
Numerical Method for Accessing the Universal Scaling Function for a Multi-Particle Discrete Time Asymmetric Exclusion Process
In the universality class of the one dimensional Kardar-Parisi-Zhang surface
growth, Derrida and Lebowitz conjectured the universality of not only the
scaling exponents, but of an entire scaling function. Since Derrida and
Lebowitz's original publication [PRL 80 209 (1998)] this universality has been
verified for a variety of continuous time, periodic boundary systems in the KPZ
universality class. Here, we present a numerical method for directly examining
the entire particle flux of the asymmetric exclusion process (ASEP), thus
providing an alternative to more difficult cumulant ratios studies. Using this
method, we find that the Derrida-Lebowitz scaling function (DLSF) properly
characterizes the large system size limit (N-->infty) of a single particle
discrete time system, even in the case of very small system sizes (N <= 22).
This fact allows us to not only verify that the DLSF properly characterizes
multiple particle discrete-time asymmetric exclusion processes, but also
provides a way to numerically solve for quantities of interest, such as the
particle hopping flux. This method can thus serve to further increase the ease
and accessibility of studies involving even more challenging dynamics, such as
the open boundary ASEP
Lambda-prophage induction modeled as a cooperative failure mode of lytic repression
We analyze a system-level model for lytic repression of lambda-phage in E.
coli using reliability theory, showing that the repressor circuit comprises 4
redundant components whose failure mode is prophage induction. Our model
reflects the specific biochemical mechanisms involved in regulation, including
long-range cooperative binding, and its detailed predictions for prophage
induction in E. coli under ultra-violet radiation are in good agreement with
experimental data.Comment: added referenc
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