Biology subjects

Vega, N.

Publications and source records attributed to Vega, N..

6 recordsLinked to original sources

bioRxiv2024

Variance in C. elegans gut bacterial load suggests complex host-microbe dynamics

Variation in bacterial composition inside a host is a result of complex dynamics of microbial community assembly, but little is known about these dynamics. To deconstruct the factors that contribute to this variation, we used a combination of experimental and modeling approaches. We found that demographic stochasticity and stationary heterogeneity in the host carrying capacity or bacterial growth rate are insufficient to explain quantitatively the variation observed in our empirical data. Instead, we found that the data can be understood if the host-bacteria system can be viewed as stochastically switching between high and low growth rates phenotypes. This suggests the dynamics significantly more complex than logistic growth used in canonical models of microbiome assembly. We develop mathematical models of this process that can explain various aspects of our data. We highlight the limitations of snapshot data in describing variation in host-associated communities and the importance of using time-series data along with mathematical models to understand microbial dynamics within a host.

biophysics↗

bioRxiv2023

Identification of conserved gene expression programs activated in multiple modes of torpor across vertebrate clades.

Torpor encompasses adaptations to diverse extreme environmental stressors such as hibernation, aestivation, brumation, and daily torpor. Here we introduce StrokeofGenus, an analytic pipeline that identifies distinct transcriptomic states and conservation of gene expression patterns across studies, tissues, and species. We use StrokeofGenus to study multiple and diverse forms of torpor from publicly available RNA-seq datasets that span eight species and two classes. We identify three transcriptionally distinct states during the cycle of heterothermia: euthermia, torpor, and interbout arousal. We also identify torpor-specific gene expression patterns that are conserved both across tissues and between species with over three hundred million years of evolutionary divergence. We further demonstrate the general conservation of gene expression patterns in multiple forms of torpor, implying a common evolutionary origin for this process. Although here we apply StrokeofGenus to analysis of torpor, it can be used to interrogate any other complex physiological processes defined by transient transcriptomic states. HIGHLIGHTSO_LIStrokeofGenus integrates orthologue annotation, non-negative matrix factorization, and transfer learning for cross-species analysis. C_LIO_LIStrokeofGenus identifies conserved topor-related gene expression patterns across divergent species and cell types. C_LIO_LIHeterothermia has three distinct transcriptomic states. C_LIO_LITorpor-specific gene expression patterns are conserved between species and forms of torpor. C_LI

physiology↗

bioRxiv2023

Maximum Likelihood Estimators For Colony Forming Units

There is a recognized need to measure the abundance of microbes in hospital environments, in the sanitation industry, and in food preparation. Doctors, microbiologists, and food safety experts have been addressing this need by using serial dilution methods to grow bacterial colonies in small enough numbers to count and, from these counts, to infer bacterial concentrations measured in Colony Forming Units (CFUs). There are two primary types of such methods: plating bacteria on a growth medium and counting their resulting colonies or counting the number of tubes at a given dilution that have growth. Traditionally, these types of data have been analyzed separately using different analytic methods. Here we build a direct correspondence between these approaches, which allows one to extend the use of the Most Probable Number (MPN) method from the liquid tubes experiments, for which it was developed, to the growth plates. We also discuss how to combine measurements taken at different dilutions, and we review several ways of analyzing colony counts, including the Poison and truncated Poison methods. For all methods, we discuss their relevant error bounds, assumptions, strengths, and weaknesses. We provide an online calculator for these estimators.

biophysics↗

bioRxiv2022

Batching inflates error rates in microbial colonization of Caenorhabditis elegans: an empirical investigation of the statistical properties of count-based data

Heterogeneity is ubiquitous across individuals in biological data, and sample batching, a form of biological averaging, inevitably loses information about this heterogeneity. The consequences for inference from biologically averaged data are frequently opaque, particularly when the underlying populations are non-normal. Here we investigate a case where biological averaging is common - count-based measurement of bacterial load in individual Caenorhabditis elegans - to empirically determine the consequences of batching. We find that both central measures and measures of variation on individual-based data contain biologically relevant information that is useful for distinguishing between groups, and that batch-based inference readily produces both false positive and false negative results in these comparisons. These results support the use of individual rather than batched samples when possible, illustrate the importance of understanding distributions across individuals within a sample frame, and indicate the need to consider effect size when drawing conclusions from biologically averaged data.

microbiology↗

bioRxiv2019

The population and evolutionary dynamics of bacteriophage: Why be temperate revisited

Bacteriophages are deemed either lytic (virulent) or temperate, respectively depending on whether their genomes are transmitted solely horizontally, or both horizontally and vertically. To elucidate the ecological and evolutionary conditions under which natural selection will favor the evolution and maintenance of lytic or temperate modes of phage replication and transmission, we use a comprehensive mathematical model of the dynamics of temperate and virulent phage in populations of bacteria sensitive and resistant to these viruses. For our numerical analysis of the properties of this model, we use parameters estimated with the temperate bacteriophage Lambda, {lambda}, its clear and virulent mutants, and E. coli sensitive and resistant - refractory to these phages. Using batch and serial transfer population dynamic and reconstruction experiments, we test the hypotheses generated from this theoretical analysis. Based on the results of this jointly theoretical and experimental study, we postulate the conditions under which natural selection will favor the evolution and maintenance of lytic and temperate modes of phage replication and transmission. A compelling and novel prediction this in silico, in vitro, and in plastico study makes is lysogenic bacteria from natural populations will be resistant-refractory to the phage for which they are lysogenic as well as lytic phage sharing the same receptors as these temperate viruses.

evolutionary biology↗

bioRxiv2019

Mucoidy, a general mechanism for maintaining lytic phage in populations of bacteria

We present evidence that phage resistance resulting from overproduction of exopolysaccharides, mucoidy, provides a general answer to the longstanding question of how lytic viruses are maintained in populations dominated by bacteria upon which they cannot replicate. In serial transfer culture, populations of mucoid E. coli MG1655 that are resistant to lytic phages with different receptors, and thereby requiring independent mutations for surface resistance, are capable of maintaining these phages with little effect on their total density. Based on the results of our analysis of a mathematical model, we postulate that the maintenance of phage in populations dominated by mucoid cells can be attributed primarily to high rates of transition from the resistant mucoid states to susceptible non-mucoid states. Our tests with both population dynamic and single cell experiments as well as DNA sequence analysis are consistent with this hypothesis. We discuss reasons for the generalized resistance of these mucoid E. coli, and the genetic and molecular mechanisms responsible for the high rate of transition from mucoid to sensitive states responsible for the maintenance of lytic phage in mucoid populations of E. coli.

microbiology↗