Biology subjects

Franz, E.

Publications and source records attributed to Franz, E..

4 recordsLinked to original sources

bioRxiv2021

phylogatR: Phylogeographic data aggregation and repurposing

Patterns of genetic diversity within species contain information about the history of that species, including how they have responded to historical climate change and how easily the organism is able to disperse across its habitat. More than 40,000 phylogeographic and population genetic investigations have been published to date, each collecting genetic data from hundreds of samples. Despite these millions of data points, meta-analyses are challenging because the synthesis of results across hundreds of studies, each using different methods and forms of analysis, is a daunting and time-consuming task. It is more efficient to proceed by repurposing existing data and using automated data analysis. To facilitate data repurposing, we created a database (phylogatR) that aggregates data from different sources and conducts automated multiple sequence alignments and data curation to provide users with nearly ready-to-analyze sets of data for thousands of species. Two types of scientific research will be made easier by phylogatR, large meta-analyses of thousands of species that can address classic questions in evolutionary biology and ecology and student- or citizen-science based investigations that will introduce a broad range of people to the analysis of genetic data. phylogatR enhances the value of existing data via the creation of software and web-based tools that enable these data to be recycled and reanalyzed and increase accessibility to big data for research labs and classroom instructors with limited computational expertise and resources.

bioinformatics↗

bioRxiv2021

Asymptomatic gut colonization by extended-spectrum beta-lactamase-producing Escherichia coli is not associated with an altered gut microbiome or metabolome in Dutch adults

BackgroundGut colonization by antibiotic resistant E. coli strains, including extended-spectrum beta-lactamase (ESBL)-producing E. coli is a risk factor for developing overt infection. The gut microbiome can provide colonization resistance against enteropathogens, but it remains unclear whether it confers resistance against potentially pathogenic ESBL-producing E. coli. MaterialsFrom a Dutch cross-sectional population study (PIENTER-3), feces from 2751 individuals were used to culture ESBL-producing bacteria. Of these, we selected 49 samples which were positive for an ESBL-producing Escherichia coli (ESBL+), and negative for a variety of variables known to affect microbiome composition. These were matched in a 1:1 ratio to ESBL- samples based on age, sex, having been abroad in the past six months and ethnicity. Shotgun metagenomic sequencing was performed and taxonomic species composition and functional annotations (microbial metabolism and carbohydrate-active enzymes) were determined. Targeted quantitative metabolic profiling (1H NMR-spectroscopy) was performed to investigate metabolomic profiles. ResultsNo differences in alpha or beta diversity were observed, nor in relative abundance, between ESBL+ and ESBL- individuals based on bacterial species level composition. Machine learning approaches based on microbiota composition did not accurately predict ESBL status (area under the receiver operating characteristic curve (AUROC)=0.53), neither when based on functional profiles. The metabolome did also not convincingly differ between ESBL groups as assessed by a variety of approaches, including machine learning through random forest (AUROC=0.61). ConclusionUsing a combination of multi-omics and machine learning approaches, we conclude that asymptomatic gut carriage of ESBL-producing E. coli is not associated with an altered microbiome composition or function. This may suggest that microbiome-mediated colonization resistance against ESBL-producing E. coli is not as relevant as it is against other enteropathogens.

microbiology↗

bioRxiv2020

Emergence and global spread of Listeria monocytogenes main clinical clonal complex

Retracing microbial emergence and spread is essential to understanding the evolution and dynamics of pathogens. The bacterial foodborne pathogen Listeria monocytogenes clonal complex 1 (Lm-CC1) is the most prevalent clonal group associated with listeriosis, and is strongly associated with cattle and dairy products. Here we analysed 2,021 Lm-CC1 isolates collected from 40 countries, since the first Lm isolation to the present day, to define its evolutionary history and population dynamics. Our results suggest that Lm-CC1 spread worldwide from North America following the Industrial Revolution through two waves of expansion, coinciding with the transatlantic livestock trade in the second half of the 19th century and the rapid growth of cattle farming in the 20th century. Lm-CC1 then firmly established at a local level, with limited inter-country spread. This study provides an unprecedented insight into Lm-CC1 phylogeography and dynamics and can contribute to effective disease surveillance to reduce the burden of listeriosis.

genomics↗

bioRxiv2020

Osteosarcoma tumors maintain intertumoral heterogeneity, even while adapting to environmental pressures that drive clonal selection

BackgroundTumors are complex tissues containing collections of phenotypically diverse malignant and nonmalignant cells. We know little of the mechanisms that govern heterogeneity of tumor cells nor of the role heterogeneity plays in overcoming stresses, such as adaptation to different microenvironments. Osteosarcoma is an ideal model for studying these mechanisms--it exhibits widespread inter- and intra-tumoral heterogeneity, predictable patterns of metastasis, and a lack of clear targetable driver mutations. Understanding the processes that facilitate adaptation to primary and metastatic microenvironments could inform the development of therapeutic targeting strategies. ResultsWe investigated single-cell RNA-sequencing profiles of 47,977 cells obtained from cell line and patient-derived xenograft models as cells adapted to growth within primary bone and metastatic lung environments. Tumor cells maintained phenotypic heterogeneity as they responded to the selective pressures imposed during bone and lung colonization. Heterogenous subsets of cells defined by distinct transcriptional profiles were maintained within bone- and lung-colonizing tumors, despite high-level selection. One prominent heterogenous feature involving glucose metabolism was clearly validated using immunofluorescence staining. Finally, using concurrent lineage tracing and single-cell transcriptomics, we found that lung colonization enriches for multiple clones with distinct transcriptional profiles that are preserved across cellular generations. ConclusionsResponse to environmental stressors occurs through complex and dynamic phenotypic adaptations. Heterogeneity is maintained, even in conditions that enforce clonal selection. These findings likely reflect the influences of developmental processes promoting diversification of tumor cell subpopulations, which are retained, even in the face of selective pressures.

cancer biology↗