scholarly journals Dual RNA-seq reveals no plastic transcriptional response of the coccidian parasiteEimeria falciformisto host immune defenses

2017 ◽  
Author(s):  
Totta Ehret ◽  
Simone Spork ◽  
Christoph Dieterich ◽  
Richard Lucius ◽  
Emanuel Heitlinger

ABSTRACTBackgroundParasites can either respond to differences in immune defenses that exist between individual hosts plastically or, alternatively, follow a genetically canalized (“hard wired”) program of infection. Assuming that large-scale functional plasticity would be discernible in the parasite transcriptome we have performed a dual RNA-seq study of the full lifecycle ofEimeria falciformisusing infected mice with different immune status (e.g. naïve versus immune animals) as models for coccidian infections.ResultsWe compared parasite and host transcriptomes (dual transcriptome) between naïve and challenge infected mice, as well as between immune competent and immune deficient ones. Mice with different immune competence show transcriptional differences as well as differences in parasite reproduction (oocyst shedding). Broad gene categories represented by differently abundant host genes indicate enrichments for immune reaction and tissue repair functions. More specifically, TGF-beta, EGF, TNF and IL-1 and IL-6 are examples of functional annotations represented differently depending on host immune status. Much in contrast, parasite transcriptomes were neither different between Coccidia isolated from immune competent and immune deficient mice, nor between those harvested from naïve and challenge infected mice. Instead, parasite transcriptomes have distinct profiles early and late in infection, characterized largely by biosynthesis or motility associated functional gene groups, respectively. Extracellular sporozoite and oocyst stages showed distinct transcriptional profiles and sporozoite transcriptomes were found enriched for species specific genes and likely pathogenicity factors.ConclusionWe propose that the niche and host-specific parasiteE. falciformisuses a genetically canalized program of infection. This program is likely fixed in an evolutionary process rather than employing phenotypic plasticity to interact with its host. In turn this might (negatively) influence the ability of the parasite to use different host species and (positively or negatively) influence its evolutionary potential for adaptation to different hosts or niches.


Author(s):  
Robin Herbrechter ◽  
Nadine Hube ◽  
Raoul Buchholz ◽  
Andreas Reiner

AbstractIonotropic glutamate receptors (iGluRs) play key roles for signaling in the central nervous system. Alternative splicing and RNA editing are well-known mechanisms to increase iGluR diversity and to provide context-dependent regulation. Earlier work on isoform identification has focused on the analysis of cloned transcripts, mostly from rodents. We here set out to obtain a systematic overview of iGluR splicing and editing in human brain based on RNA-Seq data. Using data from two large-scale transcriptome studies, we established a workflow for the de novo identification and quantification of alternative splice and editing events. We detected all canonical iGluR splice junctions, assessed the abundance of alternative events described in the literature, and identified new splice events in AMPA, kainate, delta, and NMDA receptor subunits. Notable events include an abundant transcript encoding the GluA4 amino-terminal domain, GluA4-ATD, a novel C-terminal GluD1 (delta receptor 1) isoform, GluD1-b, and potentially new GluK4 and GluN2C isoforms. C-terminal GluN1 splicing may be controlled by inclusion of a cassette exon, which shows preference for one of the two acceptor sites in the last exon. Moreover, we identified alternative untranslated regions (UTRs) and species-specific differences in splicing. In contrast, editing in exonic iGluR regions appears to be mostly limited to ten previously described sites, two of which result in silent amino acid changes. Coupling of proximal editing/editing and editing/splice events occurs to variable degree. Overall, this analysis provides the first inventory of alternative splicing and editing in human brain iGluRs and provides the impetus for further transcriptome-based and functional investigations.



BMC Genomics ◽  
2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Totta Ehret ◽  
Simone Spork ◽  
Christoph Dieterich ◽  
Richard Lucius ◽  
Emanuel Heitlinger


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lin Que ◽  
David Lukacsovich ◽  
Wenshu Luo ◽  
Csaba Földy

AbstractThe diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. In this study, we used single-cell RNA-seq in morphologically identified parvalbumin interneurons (PV-INs), and studied their transcriptomic states in the morphological, physiological, and developmental domains. Overall, we find high transcriptomic similarity among PV-INs, with few genes showing divergent expression between morphologically different types. Furthermore, PV-INs show a uniform synaptic cell adhesion molecule (CAM) profile, suggesting that CAM expression in mature PV cells does not reflect wiring specificity after development. Together, our results suggest that while PV-INs differ in anatomy and in vivo activity, their continuous transcriptomic and homogenous biophysical landscapes are not predictive of these distinct identities.



Author(s):  
Aniket Bhattacharya ◽  
Vineet Jha ◽  
Khushboo Singhal ◽  
Mahar Fatima ◽  
Dayanidhi Singh ◽  
...  

Abstract Alu repeats contribute to phylogenetic novelties in conserved regulatory networks in primates. Our study highlights how exonized Alus could nucleate large-scale mRNA-miRNA interactions. Using a functional genomics approach, we characterize a transcript isoform of an orphan gene, CYP20A1 (CYP20A1_Alu-LT) that has exonization of 23 Alus in its 3’UTR. CYP20A1_Alu-LT, confirmed by 3’RACE, is an outlier in length (9 kb 3’UTR) and widely expressed. Using publically available datasets, we demonstrate its expression in higher primates and presence in single nucleus RNA-seq of 15928 human cortical neurons. miRanda predicts ∼4700 miRNA recognition elements (MREs) for ∼1000 miRNAs, primarily originated within these 3’UTR-Alus. CYP20A1_Alu-LT could be a potential multi-miRNA sponge as it harbors ≥10 MREs for 140 miRNAs and has cytosolic localization. We further tested whether expression of CYP20A1_Alu-LT correlates with mRNAs harboring similar MRE targets. RNA-seq with conjoint miRNA-seq analysis was done in primary human neurons where we observed CYP20A1_Alu-LT to be downregulated during heat shock response and upregulated in HIV1-Tat treatment. 380 genes were positively correlated with its expression (significantly downregulated in heat shock and upregulated in Tat) and they harbored MREs for nine expressed miRNAs which were also enriched in CYP20A1_Alu-LT. MREs were significantly enriched in these 380 genes compared to random sets of differentially expressed genes (p = 8.134e-12). Gene ontology suggested involvement of these genes in neuronal development and hemostasis pathways thus proposing a novel component of Alu-miRNA mediated transcriptional modulation that could govern specific physiological outcomes in higher primates.



Author(s):  
Yan Cui ◽  
Wenqiao Wayne Yuan ◽  
Zhijian Pei

Continuous use of petroleum derived fuels is widely recognized as unsustainable due to depleting supplies and the accumulation of greenhouse gases in the environment. Renewable, carbon neutral transport fuels are needed for environmental and economic sustainabilities. Algae have been demonstrated to be one of the most promising sources for biofuel production. However, large-scale algae production and harvesting for energy manufacturing are too costly using existing methods. The approach of growing algae on solid carriers is innovative and can potentially lead to cost-effective manufacturing of algae biofuels. As cells approach to the solid surface, many factors come in to influence microbial attachment such as the surface wettability, free energy, polarity, roughness and topography. Surface wettability plays an important role in the initial cell attachment. For further contact, surface free energy and polarity are more directly related to cell-substratum attachment strength. Surface roughness and texture are species-specific parameters and have been applied widely in attachment studies.



2018 ◽  
Vol 15 (16) ◽  
pp. 5189-5202 ◽  
Author(s):  
Gustaf Granath ◽  
Håkan Rydin ◽  
Jennifer L. Baltzer ◽  
Fia Bengtsson ◽  
Nicholas Boncek ◽  
...  

Abstract. Rain-fed peatlands are dominated by peat mosses (Sphagnum sp.), which for their growth depend on nutrients, water and CO2 uptake from the atmosphere. As the isotopic composition of carbon (12,13C) and oxygen (16,18O) of these Sphagnum mosses are affected by environmental conditions, Sphagnum tissue accumulated in peat constitutes a potential long-term archive that can be used for climate reconstruction. However, there is inadequate understanding of how isotope values are influenced by environmental conditions, which restricts their current use as environmental and palaeoenvironmental indicators. Here we tested (i) to what extent C and O isotopic variation in living tissue of Sphagnum is species-specific and associated with local hydrological gradients, climatic gradients (evapotranspiration, temperature, precipitation) and elevation; (ii) whether the C isotopic signature can be a proxy for net primary productivity (NPP) of Sphagnum; and (iii) to what extent Sphagnum tissue δ18O tracks the δ18O isotope signature of precipitation. In total, we analysed 337 samples from 93 sites across North America and Eurasia using two important peat-forming Sphagnum species (S. magellanicum, S. fuscum) common to the Holarctic realm. There were differences in δ13C values between species. For S. magellanicum δ13C decreased with increasing height above the water table (HWT, R2=17 %) and was positively correlated to productivity (R2=7 %). Together these two variables explained 46 % of the between-site variation in δ13C values. For S. fuscum, productivity was the only significant predictor of δ13C but had low explanatory power (total R2=6 %). For δ18O values, approximately 90 % of the variation was found between sites. Globally modelled annual δ18O values in precipitation explained 69 % of the between-site variation in tissue δ18O. S. magellanicum showed lower δ18O enrichment than S. fuscum (−0.83 ‰ lower). Elevation and climatic variables were weak predictors of tissue δ18O values after controlling for δ18O values of the precipitation. To summarize, our study provides evidence for (a) good predictability of tissue δ18O values from modelled annual δ18O values in precipitation, and (b) the possibility of relating tissue δ13C values to HWT and NPP, but this appears to be species-dependent. These results suggest that isotope composition can be used on a large scale for climatic reconstructions but that such models should be species-specific.



2021 ◽  
Vol 8 ◽  
Author(s):  
Kim de Mutsert ◽  
Kristy A. Lewis ◽  
Eric D. White ◽  
Joe Buszowski

Coastal erosion and wetland loss are affecting Louisiana to such an extent that the loss of land between 1932 and 2016 was close to 5,000 km2. To mitigate this decline, coastal protection and restoration projects are being planned and implemented by the State of Louisiana, United States. The Louisiana Coastal Master Plan (CMP) is an adaptive management approach that provides a suite of projects that are predicted to build or maintain land and protect coastal communities. Restoring the coast with this 50-year large-scale restoration and risk reduction plan has the potential to change the biomass and distribution of economically and ecologically important fisheries species in this region. However, not restoring the coast may have negative impacts on these species due to the loss of habitat. This research uses an ecosystem model to evaluate the effects of plan implementation versus a future without action (FWOA) on the biomass and distribution of fisheries species in the estuaries over 50 years of model simulations. By simulating effects using a spatially-explicit ecosystem model, not only can the changes in biomass in response to plan implementation be evaluated, but also the distribution of species in response to the planned restoration and risk reduction projects. Simulations are performed under two relative sea level rise (SLR) scenarios to understand the effects of climate change on project performance and subsequent fisheries species biomass and distribution. Simulation output of eight economically important fisheries species shows that the plan mostly results in increases in species biomass, but that the outcomes are species-specific and basin-specific. The SLR scenario highly affects the amount of wetland habitat maintained after 50 years (with higher levels of wetland loss under increased SLR) and, subsequently, the biomass of species depending on that habitat. Species distribution results can be used to identify expected changes for specific species on a regional basis. By making this type of information available to resource managers, precautionary measures of ecosystem management and adaptation can be implemented.



2020 ◽  
Author(s):  
Ramon Viñas ◽  
Tiago Azevedo ◽  
Eric R. Gamazon ◽  
Pietro Liò

AbstractA question of fundamental biological significance is to what extent the expression of a subset of genes can be used to recover the full transcriptome, with important implications for biological discovery and clinical application. To address this challenge, we present GAIN-GTEx, a method for gene expression imputation based on Generative Adversarial Imputation Networks. In order to increase the applicability of our approach, we leverage data from GTEx v8, a reference resource that has generated a comprehensive collection of transcriptomes from a diverse set of human tissues. We compare our model to several standard and state-of-the-art imputation methods and show that GAIN-GTEx is significantly superior in terms of predictive performance and runtime. Furthermore, our results indicate strong generalisation on RNA-Seq data from 3 cancer types across varying levels of missingness. Our work can facilitate a cost-effective integration of large-scale RNA biorepositories into genomic studies of disease, with high applicability across diverse tissue types.



2020 ◽  
Author(s):  
Noel-Marie Plonski ◽  
Emily Johnson ◽  
Madeline Frederick ◽  
Heather Mercer ◽  
Gail Fraizer ◽  
...  

AbstractBackgroundAs the number of RNA-seq datasets that become available to explore transcriptome diversity increases, so does the need for easy-to-use comprehensive computational workflows. Many available tools facilitate analyses of one of the two major mechanisms of transcriptome diversity, namely, differential expression of isoforms due to alternative splicing, while the second major mechanism - RNA editing due to post-transcriptional changes of individual nucleotides – remains under-appreciated. Both these mechanisms play an essential role in physiological and diseases processes, including cancer and neurological disorders. However, elucidation of RNA editing events at transcriptome-wide level requires increasingly complex computational tools, in turn resulting in a steep entrance barrier for labs who are interested in high-throughput variant calling applications on a large scale but lack the manpower and/or computational expertise.ResultsHere we present an easy-to-use, fully automated, computational pipeline (Automated Isoform Diversity Detector, AIDD) that contains open source tools for various tasks needed to map transcriptome diversity, including RNA editing events. To facilitate reproducibility and avoid system dependencies, the pipeline is contained within a pre-configured VirtualBox environment. The analytical tasks and format conversions are accomplished via a set of automated scripts that enable the user to go from a set of raw data, such as fastq files, to publication-ready results and figures in one step. A publicly available dataset of Zika virus-infected neural progenitor cells is used to illustrate AIDD’s capabilities.ConclusionsAIDD pipeline offers a user-friendly interface for comprehensive and reproducible RNA-seq analyses. Among unique features of AIDD are its ability to infer RNA editing patterns, including ADAR editing, and inclusion of Guttman scale patterns for time series analysis of such editing landscapes. AIDD-based results show importance of diversity of ADAR isoforms, key RNA editing enzymes linked with the innate immune system and viral infections. These findings offer insights into the potential role of ADAR editing dysregulation in the disease mechanisms, including those of congenital Zika syndrome. Because of its automated all-inclusive features, AIDD pipeline enables even a novice user to easily explore common mechanisms of transcriptome diversity, including RNA editing landscapes.



2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chayaporn Suphavilai ◽  
Shumei Chia ◽  
Ankur Sharma ◽  
Lorna Tu ◽  
Rafael Peres Da Silva ◽  
...  

AbstractWhile understanding molecular heterogeneity across patients underpins precision oncology, there is increasing appreciation for taking intra-tumor heterogeneity into account. Based on large-scale analysis of cancer omics datasets, we highlight the importance of intra-tumor transcriptomic heterogeneity (ITTH) for predicting clinical outcomes. Leveraging single-cell RNA-seq (scRNA-seq) with a recommender system (CaDRReS-Sc), we show that heterogeneous gene-expression signatures can predict drug response with high accuracy (80%). Using patient-proximal cell lines, we established the validity of CaDRReS-Sc’s monotherapy (Pearson r>0.6) and combinatorial predictions targeting clone-specific vulnerabilities (>10% improvement). Applying CaDRReS-Sc to rapidly expanding scRNA-seq compendiums can serve as in silico screen to accelerate drug-repurposing studies. Availability: https://github.com/CSB5/CaDRReS-Sc.



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