12 research outputs found

    Genome-scale co-expression network comparison across escherichia coli and salmonella enterica serovar typhimurium reveals significant conservation at the regulon level of local regulators despite their dissimilar lifestyles

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    Availability of genome-wide gene expression datasets provides the opportunity to study gene expression across different organisms under a plethora of experimental conditions. In our previous work, we developed an algorithm called COMODO (COnserved MODules across Organisms) that identifies conserved expression modules between two species. In the present study, we expanded COMODO to detect the co-expression conservation across three organisms by adapting the statistics behind it. We applied COMODO to study expression conservation/divergence between Escherichia coli, Salmonella enterica, and Bacillus subtilis. We observed that some parts of the regulatory interaction networks were conserved between E. coli and S. enterica especially in the regulon of local regulators. However, such conservation was not observed between the regulatory interaction networks of B. subtilis and the two other species. We found co-expression conservation on a number of genes involved in quorum sensing, but almost no conservation for genes involved in pathogenicity across E. coli and S. enterica which could partially explain their different lifestyles. We concluded that despite their different lifestyles, no significant rewiring have occurred at the level of local regulons involved for instance, and notable conservation can be detected in signaling pathways and stress sensing in the phylogenetically close species S. enterica and E. coli. Moreover, conservation of local regulons seems to depend on the evolutionary time of divergence across species disappearing at larger distances as shown by the comparison with B. subtilis. Global regulons follow a different trend and show major rewiring even at the limited evolutionary distance that separates E. coli and S. enterica

    Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders

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    How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark the fidelity of stem cell differentiation or cell programming, or interpret the pathogenicity of noncoding variation. Here, we study histone modifications across thirteen tissues during human organogenesis. We integrate the data with transcription to build an overview of how the human genome differentially regulates alternative organ fates including by repression. Promoters from nearly 20,000 genes partition into discrete states. Key developmental gene sets are actively repressed outside of the appropriate organ without obvious bivalency. Candidate enhancers, functional in zebrafish, allow imputation of tissue-specific and shared patterns of transcription factor binding. Overlaying more than 700 noncoding mutations from patients with developmental disorders allows correlation to unanticipated target genes. Taken together, the data provide a comprehensive genomic framework for investigating normal and abnormal human development

    Developing stakeholder-driven scenarios on land sharing and land sparing – Insights from five European case studies

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    Empirical research on land sharing and land sparing has been criticized because preferences of local stakeholders, socio-economic aspects, a bundle of ecosystem services and the local context were only rarely integrated. Using storylines and scenarios is a common approach to include land use drivers and local contexts or to cope with the uncertainties of future developments. The objective of the presented research is to develop comparable participatory regional land use scenarios for the year 2030 reflecting land sharing, land sparing and more intermediate developments across five different European landscapes (Austria, Germany, Switzerland, The Netherlands and Spain). In order to ensure methodological consistency among the five case studies, a hierarchical multi-scale scenario approach was developed, which consisted of i) the selection of a common global storyline to frame a common sphere of uncertainty for all case studies, ii) the definition of three contrasting qualitative European storylines (representing developments for land sharing, land sparing and a balanced storyline), and iii) the development of three explorative case study-specific land use scenarios with regional stakeholders in workshops. Land use transition rules defined by stakeholders were used to generate three different spatially-explicit scenarios for each case study by means of high-resolution land use maps. All scenarios incorporated various aspects of land use and management to allow subsequent quantification of multiple ecosystem services and biodiversity indicators. The comparison of the final scenarios showed both common as well as diverging trends among the case studies. For instance, stakeholders identified further possibilities to intensify land management in all case studies in the land sparing scenario. In addition, in most case studies stakeholders agreed on the most preferred scenario, i.e. either land sharing or balanced, and the most likely one, i.e. balanced. However, they expressed some skepticism regarding the general plausibility of land sparing in a European context. It can be concluded that stakeholder perceptions and the local context can be integrated in land sharing and land sparing contexts subject to particular process design principles

    Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders

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    From Springer Nature via Jisc Publications RouterHistory: received 2019-10-04, accepted 2020-06-18, registration 2020-06-24, pub-electronic 2020-08-06, online 2020-08-06, collection 2020-12Publication status: PublishedFunder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265; Grant(s): CRTF, PhD studentship, MR/J003352/1, MR/L009986/1, MR/L009986/1, MR/S036121/1, MR/000638/1Funder: Academy of Medical Sciences; doi: https://doi.org/10.13039/501100000691; Grant(s): Lecturer starter grantFunder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440; Grant(s): 088566, 097820, 105610Abstract: How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark the fidelity of stem cell differentiation or cell programming, or interpret the pathogenicity of noncoding variation. Here, we study histone modifications across thirteen tissues during human organogenesis. We integrate the data with transcription to build an overview of how the human genome differentially regulates alternative organ fates including by repression. Promoters from nearly 20,000 genes partition into discrete states. Key developmental gene sets are actively repressed outside of the appropriate organ without obvious bivalency. Candidate enhancers, functional in zebrafish, allow imputation of tissue-specific and shared patterns of transcription factor binding. Overlaying more than 700 noncoding mutations from patients with developmental disorders allows correlation to unanticipated target genes. Taken together, the data provide a comprehensive genomic framework for investigating normal and abnormal human development

    COLOMBOS: Access Port for Cross-Platform Bacterial Expression Compendia

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    Background: Microarrays are the main technology for large-scale transcriptional gene expression profiling, but the large bodies of data available in public databases are not useful due to the large heterogeneity. There are several initiatives that attempt to bundle these data into expression compendia, but such resources for bacterial organisms are scarce and limited to integration of experiments from the same platform or to indirect integration of per experiment analysis results. Methodology/Principal Findings: We have constructed comprehensive organism-specific cross-platform expression compendia for three bacterial model organisms (Escherichia coli, Bacillus subtilis, and Salmonella enterica serovar Typhimurium) together with an access portal, dubbed COLOMBOS, that not only provides easy access to the compendia, but also includes a suite of tools for exploring, analyzing, and visualizing the data within these compendia. It is freely available at http://bioi.biw.kuleuven.be/colombos. The compendia are unique in directly combining expression information from different microarray platforms and experiments, and we illustrate the potential benefits of this direct integration with a case study: extending the known regulon of the Fur transcription factor of E. coli. The compendia also incorporate extensive annotations for both genes and experimental conditions; these heterogeneous data are functionally integrated in the COLOMBOS analysis tools to interactively browse and query the compendia not only for specific genes or experiments, but also metabolic pathways, transcriptional regulation mechanisms, experimental conditions, biological processes, etc. Conclusions/Significance: We have created cross-platform expression compendia for several bacterial organisms and developed a complementary access port COLOMBOS, that also serves as a convenient expression analysis tool to extract useful biological information. This work is relevant to a large community of microbiologists by facilitating the use of publicly available microarray experiments to support their research

    Model-based evaluation of land management strategies with regard to multiple ecosystem services

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    In agroecosystem management, conflicts between various services such as food provision and nutrient regulation are common. This study examined the trade-offs between selected ecosystem services such as food provision, water quantity and quality, erosion and climate regulations in an agricultural catchment in Western Switzerland. The aim was to explore the existing land use conflicts by a shift in land use and management strategy following two stakeholder-defined scenarios based on either land sparing or land sharing concepts. The Soil and Water Assessment Tool (SWAT) was used to build an agro-hydrologic model of the region, which was calibrated and validated based on daily river discharge, monthly nitrate and annual crop yield, considering uncertainties associated with land management set up and model parameterization. The results show that land sparing scenario has the highest agricultural benefit, while also the highest nitrate concentration and GHG emissions. The land sharing scenario improves water quality and climate regulation services and reduces food provision. The management changes considered in the two land use scenarios did not seem to reduce the conflict but only led to a shift in trade-offs. Water quantity and erosion regulation remain unaffected by the two scenarios
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