Microbiome Research and Multi-Omics Integration for Personalized Medicine in Asthma

Asthma is a multifactorial inflammatory disorder of the respiratory system characterized by high diversity in clinical manifestations, underlying pathological mechanisms and response to treatment. It is generally established that human microbiota plays an essential role in shaping a healthy immune response, while its perturbation can cause chronic inflammation related to a wide range of diseases, including asthma. Systems biology approaches encompassing microbiome analysis can offer valuable platforms towards a global understanding of asthma complexity and improving patients’ classification, status monitoring and therapeutic choices. In the present review, we summarize recent studies exploring the contribution of microbiota dysbiosis to asthma pathogenesis and heterogeneity in the context of asthma phenotypes–endotypes and administered medication. We subsequently focus on emerging efforts to gain deeper insights into microbiota–host interactions driving asthma complexity by integrating microbiome and host multi-omics data. One of the most prominent achievements of these research efforts is the association of refractory neutrophilic asthma with certain microbial signatures, including predominant pathogenic bacterial taxa (such as Proteobacteria phyla, Gammaproteobacteria class, especially species from Haemophilus and Moraxella genera). Overall, despite existing challenges, large-scale multi-omics endeavors may provide promising biomarkers and therapeutic targets for future development of novel microbe-based personalized strategies for diagnosis, prevention and/or treatment of uncontrollable asthma.

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Post-Translational Modifications of Proteins: Novel Insights in the Autoimmune Response in Rheumatoid Arthritis

Cells ◽

10.3390/cells8070657 ◽

2019 ◽

Vol 8 (7) ◽

pp. 657 ◽

Cited By ~ 10

Author(s):

Francesco Carubbi ◽

Alessia Alunno ◽

Roberto Gerli ◽

Roberto Giacomelli

Keyword(s):

Rheumatoid Arthritis ◽

Wide Spectrum ◽

Clinical Manifestations ◽

Autoimmune Response ◽

Response To Treatment ◽

Post Translational Modifications ◽

Wide Range ◽

Specific Proteins ◽

Modified Proteins ◽

Immunogenic Properties

Post-translational modifications (PTM) are chemical changes mostly catalyzed by enzymes that recognize specific target sequences in specific proteins. These modifications play a key role in regulating the folding of proteins, their targeting to specific subcellular compartments, their interaction with ligands or other proteins, and eventually their immunogenic properties. Citrullination is the best characterized PTM in the field of rheumatology, with antibodies anticyclic citrullinated peptides being the gold standard for the diagnosis of rheumatoid arthritis (RA). In recent years, growing evidence supports not only that a wide range of proteins are subject to citrullination and can trigger an autoimmune response in RA, but also that several other PTMs such as carbamylation and acetylation occur in patients with this disease. This induces a wide spectrum of autoantibodies, as biomarkers, with different sensitivity and specificity for diagnosis, which may be linked to peculiar clinical manifestations and/or response to treatment. The purpose of this review article is to critically summarize the available literature on antibodies against post-translationally modified proteins, in particular antibodies against citrullinated proteins (ACPA) and antibodies against modified proteins (AMPA), and outline their diagnostic and prognostic role to be implemented in clinical practice for RA patients.

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A curated transcriptome dataset collection to investigate inborn errors of immunity

10.1101/526004 ◽

2019 ◽

Author(s):

Salim Bougarn ◽

Sabri Boughorbel ◽

Damien Chaussabel ◽

Nico Marr

Keyword(s):

Web Application ◽

Large Scale ◽

Mononuclear Cells ◽

Ex Vivo ◽

Clinical Manifestations ◽

Inherited Disorders ◽

Transcriptional Responses ◽

Control Subjects ◽

A Genome ◽

Wide Range

ABSTRACTPrimary immunodeficiencies (PIDs) are a heterogeneous group of inherited disorders, frequently caused by loss-of-function and less commonly by gain-of-function mutations, which can result in susceptibility to a broad or a very narrow range of infections but also in inflammatory, allergic or malignant diseases. Owing to the wide range in clinical manifestations and variability in penetrance and expressivity, there is an urgent need to better understand the underlying molecular, cellular and immunological phenotypes in PID patients in order to improve clinical diagnosis and management. Here we have compiled a manually curated collection of public transcriptome datasets mainly obtained from human whole blood, peripheral blood mononuclear cells (PBMCs) or fibroblasts of patients with PIDs and of control subjects for subsequent meta-analysis, query and interpretation. A total of nineteen (19) datasets derived from studies of PID patients were identified and retrieved from the NCBI Gene Expression Omnibus (GEO) database and loaded in GXB, a custom web application designed for interactive query and visualization of integrated large-scale data. The dataset collection includes samples from well characterized PID patients that were stimulated ex vivo under a variety of conditions to assess the molecular consequences of the underlying, naturally occurring gene defects on a genome-wide scale. Multiple sample groupings and rank lists were generated to facilitate comparisons of the transcriptional responses between different PID patients and control subjects. The GXB tool enables browsing of a single transcript across studies, thereby providing new perspectives on the role of a given molecule across biological systems and PID patients. This dataset collection is available at: http://pid.gxbsidra.org/dm3/geneBrowser/list.

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Exploring Leishmania-Host Interaction with Reactome, a Database of Biological Pathways and Processes

10.1101/2021.03.23.436718 ◽

2021 ◽

Author(s):

Julieth Irene Murillo Silva ◽

Bijay Jassal ◽

Maria Adelaida Gomez ◽

Henning Hermjakob

Keyword(s):

Clinical Manifestations ◽

Host Cells ◽

Leishmania Infection ◽

Contextual Knowledge ◽

Growth And Survival ◽

Cell Recruitment ◽

Host Interactions ◽

Host Interaction ◽

Wide Range ◽

Infection Pathway

Leishmaniasis is a parasitic disease with a wide range of clinical manifestations. Multiple aspects of the Leishmania-host interaction, such as genetic factors and modulation of microbicidal functions in host cells, influence pathogenesis, disease severity and treatment outcome. How do scientists contend with this complexity? Here, we work towards representing detailed, contextual knowledge on Leishmania-host interactions in the Reactome pathway database to facilitate the extraction of novel mechanistic insights from existing datasets. The Reactome database uses a hierarchy of abstractions that allows for the incorporation of detailed contextual knowledge on biological processes matched to differentially expressed genes. It also includes tools for enhanced over-representation analysis that exploits this extra information. We conducted a systematic curation of published studies documenting different aspects of the Leishmania-host interaction. The 'Leishmania infection pathway' included four sub-pathways: phagocytosis, killing mechanisms, cell recruitment, and Leishmania parasite growth and survival. As proof-of-principle of the usefulness of the released pathway, we used it to analyze two previously released transcriptomic datasets of human and murine macrophages infected with Leishmania. Our results provide insights on the participation of ADORA2B signaling pathway in the modulation of IL10 and IL6 in infected macrophages. This work opens the way for other researchers to contribute to, and make use of, the Reactome database.

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Enterovirus D68: molecular biological characteristics, features of infection

MediAl ◽

10.21145/2225-0026-2019-2-40-54 ◽

2019 ◽

pp. 40-54

Author(s):

V. V. Zverev ◽

N. A. Novikova

Keyword(s):

Genetic Diversity ◽

Respiratory Tract ◽

Large Scale ◽

Clinical Manifestations ◽

The United States ◽

Biological Properties ◽

Steady Increase ◽

Acid Sensitivity ◽

Human Pathology ◽

Wide Range

Human enteroviruses (genus Enterovirus, family Picornaviridae) are infectious agents characterized by a wide range of clinical manifestations. EV-D68, associated with respiratory and neurological diseases, plays a significant role in human pathology. The virus was discovered in 1962 and has long been detected only sporadically, but since the late 2000s there has been a steady increase in cases of detection of the virus in different countries of the world. A large-scale outbreak of EV-D68 infection occurred in the United States in 2014. The virus is characterized by unique biological properties, combining the characteristics of enteroviruses and rhinoviruses, has a significant genetic diversity and is currently represented by strains of four main phylogenetic lines. Due to the acid sensitivity, the main place of virus replication are epithelial cells of the respiratory tract. EV-D68 causes mainly pathology of the upper and lower respiratory tract of varying severity, but there are numerous data on the connection of the virus with the occurrence of acute flaccid paralysis and exacerbations of asthma. The risk groups for the disease EV-D68 infection are different age groups of the population, mainly young children. The analytical review provides information on the taxonomic position and classification history, the structural structure of the virion and genome, and the genetic diversity of the virus. Much of the material is devoted to clinical and epidemiological aspects of infection. The issues of the current state of specific prevention and therapy of EV-D68 infection are highlighted. Information on approaches and methods of virus identification is given.

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A curated transcriptome dataset collection to investigate inborn errors of immunity

F1000Research ◽

10.12688/f1000research.18048.1 ◽

2019 ◽

Vol 8 ◽

pp. 188

Author(s):

Salim Bougarn ◽

Sabri Boughorbel ◽

Damien Chaussabel ◽

Nico Marr

Keyword(s):

Web Application ◽

Large Scale ◽

Mononuclear Cells ◽

Ex Vivo ◽

Clinical Manifestations ◽

Inherited Disorders ◽

Transcriptional Responses ◽

Control Subjects ◽

A Genome ◽

Wide Range

Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited disorders, frequently caused by loss-of-function and less commonly by gain-of-function mutations, which can result in susceptibility to a broad or a very narrow range of infections but also in inflammatory, allergic or malignant diseases. Owing to the wide range in clinical manifestations and variability in penetrance and expressivity, there is an urgent need to better understand the underlying molecular, cellular and immunological phenotypes in PID patients in order to improve clinical diagnosis and management. Here we have compiled a manually curated collection of public transcriptome datasets mainly obtained from human whole blood, peripheral blood mononuclear cells (PBMCs) or fibroblasts of patients with PIDs and of control subjects for subsequent meta-analysis, query and interpretation. A total of nineteen (19) datasets derived from studies of PID patients were identified and retrieved from the NCBI Gene Expression Omnibus (GEO) database and loaded in GXB, a custom web application designed for interactive query and visualization of integrated large-scale data. The dataset collection includes samples from well characterized PID patients that were stimulated ex vivo under a variety of conditions to assess the molecular consequences of the underlying, naturally occurring gene defects on a genome-wide scale. Multiple sample groupings and rank lists were generated to facilitate comparisons of the transcriptional responses between different PID patients and control subjects. The GXB tool enables browsing of a single transcript across studies, thereby providing new perspectives on the role of a given molecule across biological systems and PID patients. This dataset collection is available at http://pid.gxbsidra.org/dm3/geneBrowser/list.

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A curated transcriptome dataset collection to investigate inborn errors of immunity

F1000Research ◽

10.12688/f1000research.18048.2 ◽

2019 ◽

Vol 8 ◽

pp. 188

Author(s):

Salim Bougarn ◽

Sabri Boughorbel ◽

Damien Chaussabel ◽

Nico Marr

Keyword(s):

Web Application ◽

Large Scale ◽

Mononuclear Cells ◽

Ex Vivo ◽

Clinical Manifestations ◽

Inherited Disorders ◽

Transcriptional Responses ◽

Control Subjects ◽

A Genome ◽

Wide Range

Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited disorders, frequently caused by loss-of-function and less commonly by gain-of-function mutations, which can result in susceptibility to a broad or a very narrow range of infections but also in inflammatory, allergic or malignant diseases. Owing to the wide range in clinical manifestations and variability in penetrance and expressivity, there is an urgent need to better understand the underlying molecular, cellular and immunological phenotypes in PID patients in order to improve clinical diagnosis and management. Here we have compiled a manually curated collection of public transcriptome datasets mainly obtained from human whole blood, peripheral blood mononuclear cells (PBMCs) or fibroblasts of patients with PIDs and of control subjects for subsequent meta-analysis, query and interpretation. A total of eighteen (18) datasets derived from studies of PID patients were identified and retrieved from the NCBI Gene Expression Omnibus (GEO) database and loaded in GXB, a custom web application designed for interactive query and visualization of integrated large-scale data. The dataset collection includes samples from well characterized PID patients that were stimulated ex vivo under a variety of conditions to assess the molecular consequences of the underlying, naturally occurring gene defects on a genome-wide scale. Multiple sample groupings and rank lists were generated to facilitate comparisons of the transcriptional responses between different PID patients and control subjects. The GXB tool enables browsing of a single transcript across studies, thereby providing new perspectives on the role of a given molecule across biological systems and PID patients. This dataset collection is available at http://pid.gxbsidra.org/dm3/geneBrowser/list.

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Atypical Clinical Manifestations of Loiasis and Their Relevance for Endemic Populations

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz417 ◽

2019 ◽

Vol 6 (11) ◽

Cited By ~ 2

Author(s):

Kevin G Buell ◽

Charles Whittaker ◽

Cédric B Chesnais ◽

Paul D Jewell ◽

Sébastien D S Pion ◽

...

Keyword(s):

Large Scale ◽

Case Reports ◽

Clinical Manifestations ◽

Central Africa ◽

Epidemiological Studies ◽

True Rate ◽

Public Health Burden ◽

Wide Range ◽

Atypical Manifestations ◽

Atypical Presentations

Abstract Background Loiasis is mostly considered a relatively benign infection when compared with other filarial and parasitic diseases, with Calabar swellings and eyeworm being the most common signs. Yet, there are numerous reports in the literature of more serious sequelae. Establishing the relationship between infection and disease is a crucial first step toward estimating the burden of loiasis. Methods We conducted a systematic review of case reports containing 329 individuals and detailing clinical manifestations of loiasis with a focus on nonclassical, atypical presentations. Results Results indicate a high proportion (47%) of atypical presentations in the case reports identified, encompassing a wide range of cardiac, respiratory, gastrointestinal, renal, neurological, ophthalmological, and dermatological pathologies. Individuals with high microfilarial densities and residing in an endemic country were at greater risk of suffering from atypical manifestations. Conclusions Our findings have important implications for understanding the clinical spectrum of conditions associated with Loa loa infection, which extends well beyond the classical eyeworm and Calabar swellings. As case reports may overestimate the true rate of atypical manifestations in endemic populations, large-scale, longitudinal clinico-epidemiological studies will be required to refine our estimates and demonstrate causality between loiasis and the breadth of clinical manifestations reported. Even if the rates of atypical presentations were found to be lower, given that residents of loiasis-endemic areas are both numerous and the group most at risk of severe atypical manifestations, our conclusions support the recognition of loiasis as a significant public health burden across Central Africa.

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Quantitative assessment of NCLDV–host interactions predicted by co-occurrence analyses

10.1101/2020.10.16.342030 ◽

2020 ◽

Author(s):

Lingjie Meng ◽

Hisashi Endo ◽

Romain Blanc-Mathieu ◽

Samuel Chaffron ◽

Rodrigo Hernández-Velázquez ◽

...

Keyword(s):

Large Scale ◽

Positive Likelihood Ratio ◽

Prediction Performance ◽

Marine Environments ◽

Sequencing Data ◽

Dna Viruses ◽

Host Interactions ◽

Filtering Method ◽

Wide Range ◽

Host Relationships

AbstractNucleocytoplasmic DNA viruses (NCLDVs) are highly diverse and abundant in marine environments. However, knowledge of their hosts is limited because only a few NCLDVs have been isolated so far. Taking advantage of the recent large-scale marine metagenomics census, in silico host prediction approaches are expected to fill the gap and further expand our knowledge of virus–host relationships for unknown NCLDVs. In this study, we built co-occurrence networks of NCLDVs and eukaryotic taxa to predict virus–host interactions using Tara Oceans sequencing data. Using the positive likelihood ratio to assess the performance of host prediction for NCLDVs, we benchmarked several co-occurrence approaches and demonstrated an increase in the odds ratio of predicting true positive relationships four-fold compared with random host predictions. To further refine host predictions from high-dimensional co-occurrence networks, we developed a phylogeny-informed filtering method, Taxon Interaction Mapper, and showed it further improved the prediction performance by twelve-fold. Finally, we inferred virophage – NCLDV networks to corroborate that co-occurrence approaches are effective for predicting interacting partners of NCLDVs in marine environments.ImportanceNCLDVs can infect a wide range of eukaryotes although their life cycle is less dependent on hosts compared with other viruses. However, our understanding of NCLDV– host systems is highly limited because few of these viruses have been isolated so far. Co-occurrence information has been assumed to be useful to predict virus–host interactions. In this study, we quantitatively show the effectiveness of co-occurrence inference for NCLDV host prediction. We also improve the prediction performance with a phylogeny-guided method, which leads to a concise list of candidate host lineages for three NCLDV families. Our results underpin the usage of co-occurrence approach for metagenomic exploration of the ecology of this diverse group of viruses.

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Quantitative Assessment of Nucleocytoplasmic Large DNA Virus and Host Interactions Predicted by Co-occurrence Analyses

mSphere ◽

10.1128/msphere.01298-20 ◽

2021 ◽

Vol 6 (2) ◽

Author(s):

Lingjie Meng ◽

Hisashi Endo ◽

Romain Blanc-Mathieu ◽

Samuel Chaffron ◽

Rodrigo Hernández-Velázquez ◽

...

Keyword(s):

Large Scale ◽

Positive Likelihood Ratio ◽

Prediction Performance ◽

Marine Environments ◽

Sequencing Data ◽

Dna Viruses ◽

Host Interactions ◽

Wide Range ◽

Nucleocytoplasmic Large Dna Virus ◽

Nucleocytoplasmic Large Dna Viruses

ABSTRACT Nucleocytoplasmic large DNA viruses (NCLDVs) are highly diverse and abundant in marine environments. However, the knowledge of their hosts is limited because only a few NCLDVs have been isolated so far. Taking advantage of the recent large-scale marine metagenomics census, in silico host prediction approaches are expected to fill the gap and further expand our knowledge of virus-host relationships for unknown NCLDVs. In this study, we built co-occurrence networks of NCLDVs and eukaryotic taxa to predict virus-host interactions using Tara Oceans sequencing data. Using the positive likelihood ratio to assess the performance of host prediction for NCLDVs, we benchmarked several co-occurrence approaches and demonstrated an increase in the odds ratio of predicting true positive relationships 4-fold compared to random host predictions. To further refine host predictions from high-dimensional co-occurrence networks, we developed a phylogeny-informed filtering method, Taxon Interaction Mapper, and showed it further improved the prediction performance by 12-fold. Finally, we inferred virophage-NCLDV networks to corroborate that co-occurrence approaches are effective for predicting interacting partners of NCLDVs in marine environments. IMPORTANCE NCLDVs can infect a wide range of eukaryotes, although their life cycle is less dependent on hosts compared to other viruses. However, our understanding of NCLDV-host systems is highly limited because few of these viruses have been isolated so far. Co-occurrence information has been assumed to be useful to predict virus-host interactions. In this study, we quantitatively show the effectiveness of co-occurrence inference for NCLDV host prediction. We also improve the prediction performance with a phylogeny-guided method, which leads to a concise list of candidate host lineages for three NCLDV families. Our results underpin the usage of co-occurrence approaches for the metagenomic exploration of the ecology of this diverse group of viruses.

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Electron microscopy study of reactively sputter-deposited Ti/N films on silicon

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100131449 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1362-1363

Author(s):

V. C. Kannan ◽

A. K. Singh ◽

R. B. Irwin ◽

S. Chittipeddi ◽

F. D. Nkansah ◽

...

Keyword(s):

Integrated Circuits ◽

Large Scale ◽

Hexagonal Phase ◽

Microscopy Study ◽

Electron Microscopy Study ◽

Process Conditions ◽

Tin Films ◽

Wide Range ◽

Fcc Phase ◽

Circuits Vlsi

Titanium nitride (TiN) films have historically been used as diffusion barrier between silicon and aluminum, as an adhesion layer for tungsten deposition and as an interconnect material etc. Recently, the role of TiN films as contact barriers in very large scale silicon integrated circuits (VLSI) has been extensively studied. TiN films have resistivities on the order of 20μ Ω-cm which is much lower than that of titanium (nearly 66μ Ω-cm). Deposited TiN films show resistivities which vary from 20 to 100μ Ω-cm depending upon the type of deposition and process conditions. TiNx is known to have a NaCl type crystal structure for a wide range of compositions. Change in color from metallic luster to gold reflects the stabilization of the TiNx (FCC) phase over the close packed Ti(N) hexagonal phase. It was found that TiN (1:1) ideal composition with the FCC (NaCl-type) structure gives the best electrical property.

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