scholarly journals MicrobioLink: An Integrated Computational Pipeline to Infer Functional Effects of Microbiome–Host Interactions

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1278
Author(s):  
Tahila Andrighetti ◽  
Balazs Bohar ◽  
Ney Lemke ◽  
Padhmanand Sudhakar ◽  
Tamas Korcsmaros
Keyword(s):  
Biological Significance ◽  
Molecular Networks ◽  
Computational Pipeline ◽  
Host Proteins ◽  
Disease Pathogenesis ◽  
Host Interactions ◽  
Cellular Processes ◽  
Downstream Effects ◽  
Host Genes

Microbiome–host interactions play significant roles in health and in various diseases including autoimmune disorders. Uncovering these inter-kingdom cross-talks propels our understanding of disease pathogenesis and provides useful leads on potential therapeutic targets. Despite the biological significance of microbe–host interactions, there is a big gap in understanding the downstream effects of these interactions on host processes. Computational methods are expected to fill this gap by generating, integrating, and prioritizing predictions—as experimental detection remains challenging due to feasibility issues. Here, we present MicrobioLink, a computational pipeline to integrate predicted interactions between microbial and host proteins together with host molecular networks. Using the concept of network diffusion, MicrobioLink can analyse how microbial proteins in a certain context are influencing cellular processes by modulating gene or protein expression. We demonstrated the applicability of the pipeline using a case study. We used gut metaproteomic data from Crohn’s disease patients and healthy controls to uncover the mechanisms by which the microbial proteins can modulate host genes which belong to biological processes implicated in disease pathogenesis. MicrobioLink, which is agnostic of the microbial protein sources (bacterial, viral, etc.), is freely available on GitHub.

scholarly journals MicrobioLink: An integrated computational pipeline to infer functional effects of microbiome-host interactions

2019 ◽  
Author(s):  
Tahila Andrighetti ◽  
Balazs Bohar ◽  
Ney Lemke ◽  
Padhmanand Sudhakar ◽  
Tamas Korcsmaros
Keyword(s):  
Biological Significance ◽  
Molecular Networks ◽  
Computational Pipeline ◽  
Host Proteins ◽  
Disease Pathogenesis ◽  
Host Interactions ◽  
Cellular Processes ◽  
Downstream Effects ◽  
Host Genes

AbstractMicrobiome-host interactions play significant roles in health and in various diseases including auto-immune disorders. Uncovering these inter-kingdom cross-talks propels our understanding of disease pathogenesis, and provides useful leads on potential therapeutic targets. Despite the biological significance of microbe-host interactions, there is a big gap in understanding the downstream effects of these interactions on host processes. Computational methods are expected to fill this gap by generating, integrating and prioritizing predictions - as experimental detection remains challenging due to feasibility issues. Here, we present MicrobioLink, a computational pipeline to integrate predicted interactions between microbial and host proteins together with host molecular networks. Using the concept of network diffusion, MicrobioLink can analyse how microbial proteins in a certain context are influencing cellular processes by modulating gene or protein expression. We demonstrated the applicability of the pipeline using a case study. We used gut metaproteomic data from Crohn’s disease patients and healthy controls to uncover the mechanisms by which the microbial proteins can modulate host genes which belong to biological processes implicated in disease pathogenesis. MicrobioLink, which is agnostic of the microbial protein sources (bacterial, viral etc), is freely available on GitHub (https://github.com/korcsmarosgroup/HMIpipeline).

scholarly journals A novel stepwise integrative analysis pipeline reveals distinct microbiota-host interactions and link to symptoms in irritable bowel syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Annikka Polster ◽  
Lena Öhman ◽  
Julien Tap ◽  
Muriel Derrien ◽  
Boris Le Nevé ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Complex Variable ◽  
16S Rrna Gene Sequencing ◽  
Integrative Analysis ◽  
Rrna Gene ◽  
Analysis Pipeline ◽  
Host Interactions ◽  
Functional Relationships ◽  
Irritable Bowel ◽  
Host Genes

AbstractAlthough incompletely understood, microbiota-host interactions are assumed to be altered in irritable bowel syndrome (IBS). We, therefore, aimed to develop a novel analysis pipeline tailored for the integrative analysis of microbiota-host interactions and association to symptoms and prove its utility in a pilot cohort. A multilayer stepwise integrative analysis pipeline was developed to visualize complex variable associations. Application of the pipeline was demonstrated on a dataset of IBS patients and healthy controls (HC), using the R software package to analyze colonic host mRNA and mucosal microbiota (16S rRNA gene sequencing), as well as gastrointestinal (GI) and psychological symptoms. In total, 42 IBS patients (57% female, mean age 33.6 (range 18–58)) and 20 HC (60% female, mean age 26.8 (range 23–41)) were included. Only in IBS patients, mRNA expression of Toll-like receptor 4 and genes associated with barrier function (PAR2, OCLN, TJP1) intercorrelated closely, suggesting potential functional relationships. This host genes-based “permeability cluster” was associated to mucosa-adjacent Chlamydiae and Lentisphaerae, and furthermore associated to satiety as well as to anxiety, depression and fatigue. In both IBS patients and HC, chromogranins, secretogranins and TLRs clustered together. In IBS patients, this host genes-based “immune-enteroendocrine cluster” was associated to specific members of Firmicutes, and to depression and fatigue, whereas in HC no significant association to microbiota was identified. We have developed a stepwise integrative analysis pipeline that allowed identification of unique host-microbiota intercorrelation patterns and association to symptoms in IBS patients. This analysis pipeline may aid in advancing the understanding of complex variable associations in health and disease.

scholarly journals Competing Endogenous RNAs in Cervical Carcinogenesis: A New Layer of Complexity

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 991
Author(s):  
Fernanda Costa Brandão Berti ◽  
Sara Cristina Lobo-Alves ◽  
Camila de Freitas Oliveira-Toré ◽  
Amanda Salviano-Silva ◽  
Karen Brajão de Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Cervical Carcinogenesis ◽  
Molecular Changes ◽  
Cellular Processes ◽  
Target Mrnas ◽  
Competing Endogenous Rnas ◽  
Cervical Cells ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs) regulate gene expression by binding to complementary sequences within target mRNAs. Apart from working ‘solo’, miRNAs may interact in important molecular networks such as competing endogenous RNA (ceRNA) axes. By competing for a limited pool of miRNAs, transcripts such as long noncoding RNAs (lncRNAs) and mRNAs can regulate each other, fine-tuning gene expression. Several ceRNA networks led by different lncRNAs—described here as lncRNA-mediated ceRNAs—seem to play essential roles in cervical cancer (CC). By conducting an extensive search, we summarized networks involved in CC, highlighting the major impacts of such dynamic molecular changes over multiple cellular processes. Through the sponging of distinct miRNAs, some lncRNAs as HOTAIR, MALAT1, NEAT1, OIP5-AS1, and XIST trigger crucial molecular changes, ultimately increasing cell proliferation, migration, invasion, and inhibiting apoptosis. Likewise, several lncRNAs seem to be a sponge for important tumor-suppressive miRNAs (as miR-140-5p, miR-143-3p, miR-148a-3p, and miR-206), impairing such molecules from exerting a negative post-transcriptional regulation over target mRNAs. Curiously, some of the involved mRNAs code for important proteins such as PTEN, ROCK1, and MAPK1, known to modulate cell growth, proliferation, apoptosis, and adhesion in CC. Overall, we highlight important lncRNA-mediated functional interactions occurring in cervical cells and their closely related impact on cervical carcinogenesis.

scholarly journals Chikungunya and Zika Viruses: Co-Circulation and the Interplay between Viral Proteins and Host Factors

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 448
Author(s):  
Sineewanlaya Wichit ◽  
Nuttamonpat Gumpangseth ◽  
Rodolphe Hamel ◽  
Sakda Yainoy ◽  
Siwaret Arikit ◽  
...  
Keyword(s):  
Antiviral Drug ◽  
Virus Transmission ◽  
Antiviral Agent ◽  
Viral Proteins ◽  
Targeted Therapeutics ◽  
Limited Information ◽  
Mosquito Vectors ◽  
Host Proteins ◽  
Host Interactions ◽  
Viral Host Interactions

Chikungunya and Zika viruses, both transmitted by mosquito vectors, have globally re-emerged over for the last 60 years and resulted in crucial social and economic concerns. Presently, there is no specific antiviral agent or vaccine against these debilitating viruses. Understanding viral–host interactions is needed to develop targeted therapeutics. However, there is presently limited information in this area. In this review, we start with the updated virology and replication cycle of each virus. Transmission by similar mosquito vectors, frequent co-circulation, and occurrence of co-infection are summarized. Finally, the targeted host proteins/factors used by the viruses are discussed. There is an urgent need to better understand the virus–host interactions that will facilitate antiviral drug development and thus reduce the global burden of infections caused by arboviruses.

scholarly journals Viruses go modular

2020 ◽  
Vol 295 (14) ◽  
pp. 4604-4616 ◽  
Author(s):  
Ariel Shepley-McTaggart ◽  
Hao Fan ◽  
Marius Sudol ◽  
Ronald N. Harty
Keyword(s):  
Hippo Pathway ◽  
Host Proteins ◽  
Dna Viruses ◽  
Ww Domain ◽  
Ww Domains ◽  
Host Interactions ◽  
New Class ◽  
Domain Interactions ◽  
Molecular Aspects ◽  
The Hippo Pathway

The WW domain is a modular protein structure that recognizes the proline-rich Pro-Pro-x-Tyr (PPxY) motif contained in specific target proteins. The compact modular nature of the WW domain makes it ideal for mediating interactions between proteins in complex networks and signaling pathways of the cell (e.g. the Hippo pathway). As a result, WW domains play key roles in a plethora of both normal and disease processes. Intriguingly, RNA and DNA viruses have evolved strategies to hijack cellular WW domain–containing proteins and thereby exploit the modular functions of these host proteins for various steps of the virus life cycle, including entry, replication, and egress. In this review, we summarize key findings in this rapidly expanding field, in which new virus-host interactions continue to be identified. Further unraveling of the molecular aspects of these crucial virus-host interactions will continue to enhance our fundamental understanding of the biology and pathogenesis of these viruses. We anticipate that additional insights into these interactions will help support strategies to develop a new class of small-molecule inhibitors of viral PPxY-host WW-domain interactions that could be used as antiviral therapeutics.

Spatial and temporal turnover of parasite species and parasite-host interactions: a case study with fleas and gamasid mites parasitic on small mammals

2020 ◽  
Vol 119 (7) ◽  
pp. 2093-2104
Author(s):  
Boris R. Krasnov ◽  
Natalia P. Korallo-Vinarskaya ◽  
Maxim V. Vinarski ◽  
Irina S. Khokhlova
Keyword(s):  
Small Mammals ◽  
Parasite Species ◽  
Host Interactions ◽  
Gamasid Mites ◽  
Temporal Turnover

scholarly journals System-Based Approaches to Delineate the Antiviral Innate Immune Landscape

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1196
Author(s):  
Karsten Krey ◽  
Aleksandra W. Babnis ◽  
Andreas Pichlmair
Keyword(s):  
Large Scale ◽  
Innate Immune ◽  
Host Interactions ◽  
Interferon Stimulated Genes ◽  
Cellular Processes ◽  
Virus Inhibition ◽  
Cellular Factors ◽  
Functional Factors ◽  
Infected Cells ◽  
Screening Approaches

Viruses pose substantial challenges for society, economy, healthcare systems, and research. Their distinctive pathologies are based on specific interactions with cellular factors. In order to develop new antiviral treatments, it is of central importance to understand how viruses interact with their host and how infected cells react to the virus on a molecular level. Invading viruses are commonly sensed by components of the innate immune system, which is composed of a highly effective yet complex network of proteins that, in most cases, mediate efficient virus inhibition. Central to this process is the activity of interferons and other cytokines that coordinate the antiviral response. So far, numerous methods have been used to identify how viruses interact with cellular processes and revealed that the innate immune response is highly complex and involves interferon-stimulated genes and their binding partners as functional factors. Novel approaches and careful experimental design, combined with large-scale, high-throughput methods and cutting-edge analysis pipelines, have to be utilized to delineate the antiviral innate immune landscape at a global level. In this review, we describe different currently used screening approaches, how they contributed to our knowledge on virus–host interactions, and essential considerations that have to be taken into account when planning such experiments.

Recent advances in network medicine: From disease mechanisms to new treatment strategies

2020 ◽  
Vol 26 (5) ◽  
pp. 609-615
Author(s):  
Ítalo Faria do Valle
Keyword(s):  
Molecular Mechanisms ◽  
Biological Significance ◽  
Treatment Strategies ◽  
Molecular Networks ◽  
Network Medicine ◽  
Disease Mechanisms ◽  
Protein Interactome ◽  
Cellular Context ◽  
Human Proteins ◽  
New Treatment

Conventional reductionist approaches have guided most of our understanding in disease diagnostic and treatment. However, most diseases are not consequence of perturbations in a single protein or metabolite, but rather of the effect that these perturbations have in their cellular context. The emerging field of network medicine offers a set of tools to explore molecular networks and to retrieve insights about mechanisms of different diseases. The study of the protein interactome, the map of physical interactions among human proteins, revealed that disease proteins tend to interact with each other, linking diseases to well-defined interactome neighborhoods. These disease-associated neighborhoods have been defined as disease modules, and they can uncover the biological significance of genes identified by genetic studies, reveal molecular mechanisms that connect different phenotypes, and help identify new pharmacological strategies for disease treatment. Therefore, network medicine offers a framework in which the complexity of different aspects of multiple sclerosis can be explored in an integrative fashion, which can ultimately provide insights about disease mechanisms and treatment.

scholarly journals Alternative Experimental Models for Studying Influenza Proteins, Host–Virus Interactions and Anti-Influenza Drugs

2019 ◽  
Vol 12 (4) ◽  
pp. 147 ◽  
Author(s):  
Sonja C. J. H. Chua ◽  
Hui Qing Tan ◽  
David Engelberg ◽  
Lina H. K. Lim
Keyword(s):  
Protein Function ◽  
Viral Infections ◽  
Experimental Models ◽  
Host Proteins ◽  
Physiological Basis ◽  
Host Interactions ◽  
Experimental Systems ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Unique Potential

Ninety years after the discovery of the virus causing the influenza disease, this malady remains one of the biggest public health threats to mankind. Currently available drugs and vaccines only partially reduce deaths and hospitalizations. Some of the reasons for this disturbing situation stem from the sophistication of the viral machinery, but another reason is the lack of a complete understanding of the molecular and physiological basis of viral infections and host–pathogen interactions. Even the functions of the influenza proteins, their mechanisms of action and interaction with host proteins have not been fully revealed. These questions have traditionally been studied in mammalian animal models, mainly ferrets and mice (as well as pigs and non-human primates) and in cell lines. Although obviously relevant as models to humans, these experimental systems are very complex and are not conveniently accessible to various genetic, molecular and biochemical approaches. The fact that influenza remains an unsolved problem, in combination with the limitations of the conventional experimental models, motivated increasing attempts to use the power of other models, such as low eukaryotes, including invertebrate, and primary cell cultures. In this review, we summarized the efforts to study influenza in yeast, Drosophila, zebrafish and primary human tissue cultures and the major contributions these studies have made toward a better understanding of the disease. We feel that these models are still under-utilized and we highlight the unique potential each model has for better comprehending virus–host interactions and viral protein function.

Epigenetic regulation of geminivirus pathogenesis: a case of relentless recalibration of defence responses in plants

2020 ◽  
Vol 71 (22) ◽  
pp. 6890-6906 ◽  
Author(s):  
Fauzia Zarreen ◽  
Supriya Chakraborty
Keyword(s):  
Viral Genome ◽  
Current Knowledge ◽  
Plant Viruses ◽  
Limited Evidence ◽  
Host Proteins ◽  
Crop Species ◽  
Cellular Processes ◽  
Wide Range ◽  
Defence Responses ◽  
Epigenetic Processes

Abstract Geminiviruses constitute one of the largest families of plant viruses and they infect many economically important crops. The proteins encoded by the single-stranded DNA genome of these viruses interact with a wide range of host proteins to cause global dysregulation of cellular processes and help establish infection in the host. Geminiviruses have evolved numerous mechanisms to exploit host epigenetic processes to ensure the replication and survival of the viral genome. Here, we review our current knowledge of diverse epigenetic processes that have been implicated in the regulation of geminivirus pathogenesis, including DNA methylation, histone post-transcriptional modification, chromatin remodelling, and nucleosome repositioning. In addition, we discuss the currently limited evidence of host epigenetic defence responses that are aimed at counteracting geminivirus infection, and the potential for exploiting these responses for the generation of resistance against geminiviruses in crop species.

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