scholarly journals The signal and the noise - characteristics of antisense RNA in complex microbial communities

2019 ◽  
Author(s):  
Thomas Yssing Michaelsen ◽  
Jakob Brandt ◽  
Caitlin Singleton ◽  
Rasmus Hansen Kirkegaard ◽  
Nicola Segata ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microbial Communities ◽  
Antisense Rna ◽  
High Throughput Sequencing ◽  
Antisense Transcription ◽  
Individual Species ◽  
List Type ◽  
Additional Information ◽  
Noise Characteristics ◽  
Insight Into

AbstractHigh-throughput sequencing has allowed unprecedented insight into the composition and function of complex microbial communities. With the onset of metatranscriptomics, it is now possible to interrogate the transcriptome of multiple organisms simultaneously to get an overview of the gene expression of the entire community. Studies have successfully used metatranscriptomics to identify and describe relationships between gene expression levels and community characteristics. However, metatranscriptomic datasets contain a rich suite of additional information which is just beginning to be explored. In this minireview we discuss the different computational strategies for handling antisense expression in metatranscriptomic samples and highlight their potentially detrimental effects on downstream analysis and interpretation. We also surveyed the antisense transcriptome of multiple genomes and metagenome-assembled genomes (MAGs) from five different datasets and found high variability in the level of antisense transcription for individual species which were consistent across samples. Importantly, we tested the hypothesis that antisense transcription is primarily the product of transcriptional noise and found mixed support, suggesting that the total observed antisense RNA in complex communities arises from a compounded effect of both random, biological and technical factors. Antisense transcription can provide a rich set of information, from technical details about data quality to novel insight into the biology of complex microbial communities.Key pointsSeveral fundamentally different approaches are used to handle antisense RNAPrevalence of antisense RNA is highly variable between communities, genomes, and genes.Antisense RNA is likely an opaque mixture of technical, biological and random effects

scholarly journals The Signal and the Noise: Characteristics of Antisense RNA in Complex Microbial Communities

mSystems ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Thomas Yssing Michaelsen ◽  
Jakob Brandt ◽  
Caitlin Margaret Singleton ◽  
Rasmus Hansen Kirkegaard ◽  
Johanna Wiesinger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microbial Communities ◽  
Antisense Rna ◽  
Antisense Transcription ◽  
Individual Species ◽  
Data Sets ◽  
Antisense Expression ◽  
Noise Characteristics ◽  
Starting Point ◽  
Insight Into

ABSTRACT High-throughput sequencing has allowed unprecedented insight into the composition and function of complex microbial communities. With metatranscriptomics, it is possible to interrogate the transcriptomes of multiple organisms simultaneously to get an overview of the gene expression of the entire community. Studies have successfully used metatranscriptomics to identify and describe relationships between gene expression levels and community characteristics. However, metatranscriptomic data sets contain a rich suite of additional information that is just beginning to be explored. Here, we focus on antisense expression in metatranscriptomics, discuss the different computational strategies for handling it, and highlight the strengths but also potentially detrimental effects on downstream analysis and interpretation. We also analyzed the antisense transcriptomes of multiple genomes and metagenome-assembled genomes (MAGs) from five different data sets and found high variability in the levels of antisense transcription for individual species, which were consistent across samples. Importantly, we challenged the conceptual framework that antisense transcription is primarily the product of transcriptional noise and found mixed support, suggesting that the total observed antisense RNA in complex communities arises from the combined effect of unknown biological and technical factors. Antisense transcription can be highly informative, including technical details about data quality and novel insight into the biology of complex microbial communities. IMPORTANCE This study systematically evaluated the global patterns of microbial antisense expression across various environments and provides a bird’s-eye view of general patterns observed across data sets, which can provide guidelines in our understanding of antisense expression as well as interpretation of metatranscriptomic data in general. This analysis highlights that in some environments, antisense expression from microbial communities can dominate over regular gene expression. We explored some potential drivers of antisense transcription, but more importantly, this study serves as a starting point, highlighting topics for future research and providing guidelines to include antisense expression in generic bioinformatic pipelines for metatranscriptomic data.

scholarly journals Regulation of antisense RNA expression during cardiac MHC gene switching in response to pressure overload

2006 ◽  
Vol 290 (6) ◽  
pp. H2351-H2361 ◽  
Author(s):  
F. Haddad ◽  
A. X. Qin ◽  
P. W. Bodell ◽  
L. Y. Zhang ◽  
H. Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Left Ventricle ◽  
Mrna Expression ◽  
Antisense Rna ◽  
Pressure Overload ◽  
Antisense Transcription ◽  
Regulatory Sequences ◽  
Rna Regulation ◽  
Regulation Scheme ◽  
Antisense Regulation

Hypertension has been shown to cause cardiac hypertrophy and a shift in myosin heavy chain (MHC) gene expression from the faster α- to slower β-MHC isoform. The expression of the β- and α-MHC pre-mRNAs, mRNAs, as well as the newly discovered antisense β-RNA were analyzed in three regions of the normal control (NC) and 12-day pressure-overloaded (AbCon) hearts: the left ventricle apex, left ventricle base, and the septum. The RNA analyses in the AbCon heart targeted both the 5′ and the 3′ ends of each RNA molecule. β-MHC mRNA expression significantly increased relative to control in all three regions, regardless of the target site (5′ or 3′ end). In contrast, β-MHC pre-mRNA expression in the AbCon heart depended on the site of the measurement (5′ vs. 3′ end). For example, whereas the pre-mRNA did not change when targeted at the 3′ end (last intron), it increased significantly in the AbCon heart when measurement targeted the 5′ end (2nd intron) of the 25-kb molecule. Analyses of the antisense β-RNA revealed that its expression in the AbCon heart was significantly decreased relative to control regardless of its measurement site. A negative correlation was observed between the β-mRNA expression and the antisense β-RNA ( P < 0.05), suggesting an inhibitory role of antisense RNA on the sense β-MHC gene expression. In contrast, a positive correlation was observed between the antisense β-RNA and the α-MHC pre-mRNA ( P < 0.05). This latter observation along with the α-MHC gene position relative to that of the β-antisense suggest that the α-MHC sense and β-antisense transcription are coregulated likely via common intergenic regulatory sequences. Our results suggest that the increased β-MHC expression in the AbCon heart not only is the result of increased β-MHC transcription but also involves an antisense β-RNA regulation scheme. Although the exact mechanism concerning antisense regulation is not clear, it could involve modulation of both transcriptional activity of the β-MHC gene and posttranscriptional processing.

Does everything now make (anti)sense?

2006 ◽  
Vol 34 (6) ◽  
pp. 1148-1150 ◽  
Author(s):  
J.A. Timmons ◽  
L. Good
Keyword(s):  
Gene Expression ◽  
Antisense Rna ◽  
Functional Annotation ◽  
Rna World ◽  
Antisense Transcription ◽  
Functional Importance ◽  
Protein Coding ◽  
Species Diversification ◽  
Mammalian Genomes ◽  
Powerful Mechanism

The data generated by the FANTOM (Functional Annotation of Mouse) consortium, Compugen and Affymetrix have collectively provided evidence that most of the mammalian genomes are actively transcribed. The emergence of an antisense RNA world brings new practical complexities to the study and detection of gene expression. However, we also need to address the fundamental questions regarding the functional importance of these molecules. In this brief paper, we focus on non-coding natural antisense transcription, as it appears to be a potentially powerful mechanism for extending the complexity of the protein coding genome, which is currently unable to explain inter-species diversification.

Exploiting XGBoost For Predicting Enhancer-Promoter Interactions.

2020 ◽  
Vol 15 ◽  
Author(s):  
Xiaojuan Yu ◽  
Jianguo Zhou ◽  
Mingming Zhao ◽  
Chao Yi ◽  
Qing Duan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Genetic Basis ◽  
High Throughput Sequencing ◽  
The Other ◽  
Proximal Promoter ◽  
Sequence Feature ◽  
Distal Enhancer ◽  
Recent Emergence ◽  
Insight Into

: It is well-known that gene expression and disease control are co-regulated by the interaction between the distal enhancer and the proximal promoter, and the study of enhancer promoter interactions (EPIs) can help us to gain insight into the genetic basis of diseases. Although the recent emergence of some high-throughput sequencing methods have given us a deeper understanding of EPIs, accurate prediction of EPIs still have some limitations. In this paper, we trained a XGBoost based model and introduced two sets of features (i.e. epigenomic and sequence feature) to predict the interactions between the enhancer and the promoter in different cell lines. We compared XGBoost with the other four methods. Extensive experimental results have shown that XGBoost based method is effective in predicting EPIs across three cell lines. Especially epigenomic and sequence features can boost prediction.

scholarly journals Microbiota Composition and Functional Profiling Throughout the Gastrointestinal Tract of Commercial Weaning Piglets

2019 ◽  
Vol 7 (9) ◽  
pp. 343 ◽  
Author(s):  
Gresse ◽  
Chaucheyras Durand ◽  
Dunière ◽  
Blanquet-Diot ◽  
Forano
Keyword(s):  
Microbial Communities ◽  
Digestive Tract ◽  
High Throughput Sequencing ◽  
Archaeal Community ◽  
Short Chain Fatty Acids ◽  
Structural Level ◽  
Additional Information ◽  
Functional Profiling ◽  
Enteric Infections ◽  
Weaning Piglets

Dietary, environmental, and social stresses induced by weaning transition in pig production are associated with alterations of gut microbiota, diarrhea, and enteric infections. With the boom of -omic technologies, numerous studies have investigated the dynamics of fecal bacterial communities of piglets throughout weaning but much less research has been focused on the composition and functional properties of microbial communities inhabiting other gastrointestinal segments. The objective of the present study was to bring additional information about the piglet bacterial and archaeal microbiota throughout the entire digestive tract, both at the structural level by using quantitative PCR and high-throughput sequencing, and on functionality by measurement of short-chain fatty acids and predictions using Tax4Fun tool. Our results highlighted strong structural and functional differences between microbial communities inhabiting the fore and the lower gut as well as a quantitatively important archaeal community in the hindgut. The presence of opportunistic pathogens was also noticed throughout the entire digestive tract and could trigger infection emergence. Understanding the role of the intestinal piglet microbiota at weaning could provide further information about the etiology of post-weaning infections and lead to the development of effective preventive solutions.

scholarly journals Differential gene expression and the importance of regulatory ncRNAs in acidophilic microorganisms

2019 ◽  
Author(s):  
Daniela S. Aliaga Goltsman ◽  
Loren Hauser ◽  
Mauna Dasari ◽  
Brian C. Thomas ◽  
Jillian F. Banfield
Keyword(s):  
Gene Expression ◽  
Microbial Communities ◽  
Environmental Conditions ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Acidophilic Microorganisms ◽  
Sense Strand ◽  
Acidic Conditions ◽  
Group Ii ◽  
Insight Into

ABSTRACTGene expression profiles provide insight into how microorganisms respond to changing environmental conditions. However, few studies have integrated expression profile analyses of both coding genes and non-coding RNAs (ncRNAs) to characterize the functional activity of microbial community members. Here, we defined gene expression profiles from environmental and laboratory-grown acidophilic biofilms using RNASeq. In total, 15.8 million Illumina reads were mapped to the genomes of 26 acidophilic microorganisms and nine viruses reconstructed from the Richmond Mine at Iron Mountain, California. More than 99% of the genome was transcribed in three Leptospirillum species, and > 80% in the archaea G-plasma and Ferroplasma Type II. High gene expression by G-plasma and the Leptospirillum Group II UBA strain correlated with extremely acidic conditions, whereas high transcriptional expression of Leptospirillum Group III and Leptospirillum Group II 5way-CG strain occurred under higher pH and lower temperature. While expression of CRISPR Cas genes occurs on the sense strand, expression of the CRISPR loci occurs on the antisense strand in the Leptospirilli. A novel riboswitch associated with the biosynthetic pathway for the osmolyte ectoine was upregulated when each specific Leptospirillum Group II strain was growing under the conditions most favorable for it. Newly described ncRNAs associated with CO dehydrogenase (CODH) suggest regulation of expression of CODH as a CO sensor in mature biofilms in the Leptospirilli. Results reveal the ways in which environmental conditions shape transcriptional profiles of organisms growing in acidophilic microbial communities and highlight the significance of ncRNAs in regulating gene expression.IMPORTANCEMicroorganisms play important roles in environmental acidification and in metal-recovery based bioleaching processes. Therefore, characterizing how actively growing microbial communities respond to different environments is key to understanding their role in those processes. Microorganisms express their genes, both coding and non-coding, differently depending on environmental factors, thus evaluating community expression profiles inform about the ecology of actively growing microorganisms. Here we used community transcriptomic analyses to characterize gene expression profiles from biofilm communities growing under extremely acidic conditions. Results expand our knowledge of how acidophilic microorganisms respond to changes in their environment and provide insight into possible gene regulation mechanisms.

scholarly journals RNA Phage Biology in a Metagenomic Era

Viruses ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 386 ◽  
Author(s):  
Julie Callanan ◽  
Stephen Stockdale ◽  
Andrey Shkoporov ◽  
Lorraine Draper ◽  
R. Ross ◽  
...  
Keyword(s):  
Dark Matter ◽  
Microbial Communities ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Rna Viruses ◽  
Biological Significance ◽  
Relevant Information ◽  
Biological Features ◽  
Insight Into ◽  
Rna Phage

The number of novel bacteriophage sequences has expanded significantly as a result of many metagenomic studies of phage populations in diverse environments. Most of these novel sequences bear little or no homology to existing databases (referred to as the “viral dark matter”). Also, these sequences are primarily derived from DNA-encoded bacteriophages (phages) with few RNA phages included. Despite the rapid advancements in high-throughput sequencing, few studies enrich for RNA viruses, i.e., target viral rather than cellular fraction and/or RNA rather than DNA via a reverse transcriptase step, in an attempt to capture the RNA viruses present in a microbial communities. It is timely to compile existing and relevant information about RNA phages to provide an insight into many of their important biological features, which should aid in sequence-based discovery and in their subsequent annotation. Without comprehensive studies, the biological significance of RNA phages has been largely ignored. Future bacteriophage studies should be adapted to ensure they are properly represented in phageomic studies.

scholarly journals Metaproteomics: Much More than Measuring Gene Expression in Microbial Communities

mSystems ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Manuel Kleiner
Keyword(s):  
Gene Expression ◽  
Community Structure ◽  
Microbial Community ◽  
Microbial Communities ◽  
Large Scale ◽  
Molecular Level ◽  
Carbon Sources ◽  
Community Members ◽  
Insight Into

ABSTRACT Metaproteomics is the large-scale identification and quantification of proteins from microbial communities and thus provides direct insight into the phenotypes of microorganisms on the molecular level. Initially, metaproteomics was mainly used to assess the “expressed” metabolism and physiology of microbial community members. However, recently developed metaproteomic tools allow quantification of per-species biomass to determine community structure, in situ carbon sources of community members, and the uptake of labeled substrates by community members. In this perspective, I provide a brief overview of the questions that we can currently address, as well as new metaproteomics-based approaches that we and others are developing to address even more questions in the study of microbial communities and plant and animal microbiota. I also highlight some areas and technologies where I anticipate developments and potentially major breakthroughs in the next 5 years and beyond.

scholarly journals HALPER facilitates the identification of regulatory element orthologs across species

2020 ◽  
Vol 36 (15) ◽  
pp. 4339-4340 ◽  
Author(s):  
Xiaoyu Zhang ◽  
Irene M Kaplow ◽  
Morgan Wirthlin ◽  
Tae Yoon Park ◽  
Andreas R Pfenning
Keyword(s):  
Gene Expression ◽  
High Throughput Sequencing ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Supplementary Information ◽  
Individual Species ◽  
Cell Type Specificity ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Protein Coding

Abstract Summary Diverse traits have evolved through cis-regulatory changes in genome sequence that influence the magnitude, timing and cell type-specificity of gene expression. Advances in high-throughput sequencing and regulatory genomics have led to the identification of regulatory elements in individual species, but these genomic regions remain difficult to align across taxonomic orders due to their lack of sequence conservation relative to protein coding genes. The groundwork for tracing the evolution of regulatory elements is provided by the recent assembly of hundreds of genomes, the generation of reference-free Cactus multiple sequence alignments of these genomes, and the development of the halLiftover tool for mapping regions across these alignments. We present halLiftover Post-processing for the Evolution of Regulatory Elements (HALPER), a tool for constructing contiguous regulatory element orthologs from the outputs of halLiftover. We anticipate that this tool will enable users to efficiently identify orthologs of regulatory elements across hundreds of species, providing novel insights into the evolution of traits that have evolved through gene expression. Availability and implementation HALPER is implemented in python and available on github: https://github.com/pfenninglab/halLiftover-postprocessing. Supplementary information Supplementary data are available at Bioinformatics online.

Nanoparticle-plasma Membrane Interactions: Thermodynamics, Toxicity and Cellular Response

2020 ◽  
Vol 27 (20) ◽  
pp. 3330-3345
Author(s):  
Ana G. Rodríguez-Hernández ◽  
Rafael Vazquez-Duhalt ◽  
Alejandro Huerta-Saquero
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Cellular Response ◽  
Cellular Level ◽  
Membrane Interactions ◽  
Daily Lives ◽  
Cellular Physiology ◽  
Associated Proteins ◽  
First Contact ◽  
Insight Into

Nanomaterials have become part of our daily lives, particularly nanoparticles contained in food, water, cosmetics, additives and textiles. Nanoparticles interact with organisms at the cellular level. The cell membrane is the first protective barrier against the potential toxic effect of nanoparticles. This first contact, including the interaction between the cell membranes -and associated proteins- and the nanoparticles is critically reviewed here. Nanoparticles, depending on their toxicity, can cause cellular physiology alterations, such as a disruption in cell signaling or changes in gene expression and they can trigger immune responses and even apoptosis. Additionally, the fundamental thermodynamics behind the nanoparticle-membrane and nanoparticle-proteins-membrane interactions are discussed. The analysis is intended to increase our insight into the mechanisms involved in these interactions. Finally, consequences are reviewed and discussed.

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