A comprehensive collection of systems biology data characterizing the host response to viral infection

The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). By comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection

The Infectious Disease Ontology in the Age of COVID-19

The Infectious Disease Ontology (IDO) is a suite of interoperable ontology modules that aims to provide coverage of all aspects of the infectious disease domain, including biomedical research, clinical care, and public health. IDO Core is designed to be a disease and pathogen neutral ontology, covering just those types of entities and relations that are relevant to infectious diseases generally. IDO Core is then extended by a collection of ontology modules focusing on specific diseases and pathogens. In this paper we present applications of IDO Core within various areas of infectious disease research, together with an overview of all IDO extension ontologies and the methodology on the basis of which they are built. We also survey recent developments involving IDO, including the creation of IDO Virus; the Coronaviruses Infectious Disease Ontology (CIDO); and an extension of CIDO focused on COVID-19 (IDO-CovID-19).We also discuss how these ontologies might assist in information-driven efforts to deal with the ongoing COVID-19 pandemic, to accelerate data discovery in the early stages of future pandemics, and to promote reproducibility of infectious disease research

Integrating the landscape epidemiology and genetics of RNA viruses: rabies in domestic dogs as a model

Landscape epidemiology and landscape genetics combine advances in molecular techniques, spatial analyses and epidemiological models to generate a more real-world understanding of infectious disease dynamics and provide powerful new tools for the study of RNA viruses. Using dog rabies as a model we have identified how key questions regarding viral spread and persistence can be addressed using a combination of these techniques. In contrast to wildlife rabies, investigations into the landscape epidemiology of domestic dog rabies requires more detailed assessment of the role of humans in disease spread, including the incorporation of anthropogenic landscape features, human movements and socio-cultural factors into spatial models. In particular, identifying and quantifying the influence of anthropogenic features on pathogen spread and measuring the permeability of dispersal barriers are important considerations for planning control strategies, and may differ according to cultural, social and geographical variation across countries or continents. Challenges for dog rabies research include the development of metapopulation models and transmission networks using genetic information to uncover potential source/sink dynamics and identify the main routes of viral dissemination. Information generated from a landscape genetics approach will facilitate spatially strategic control programmes that accommodate for heterogeneities in the landscape and therefore utilise resources in the most cost-effective way. This can include the efficient placement of vaccine barriers, surveillance points and adaptive management for large-scale control programmes

Surveillance and response systems for elimination of tropical diseases : summary of a thematic series in infectious diseases of poverty

The peer-reviewed journal Infectious Diseases of Poverty provides a new platform to engage with, and disseminate in an open-access format, science outside traditional disciplinary boundaries. The current piece reviews a thematic series on surveillance-response systems for elimination of tropical diseases. Overall, 22 contributions covering a broad array of diseases are featured - i.e. clonorchiasis, dengue, hepatitis, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), H7N9 avian influenza, lymphatic filariasis, malaria, Middle East respiratory syndrome (MERS), rabies, schistosomiasis and tuberculosis (TB). There are five scoping reviews, a commentary, a letter to the editor, an opinion piece and an editorial pertaining to the theme "Elimination of tropical disease through surveillance and response". The remaining 13 articles are original contributions mainly covering (i) drug resistance; (ii) innovation and validation in the field of mathematical modelling; (iii) elimination of infectious diseases; and (iv) social media reports on disease outbreak notifications released by national health authorities. Analysis of the authors' affiliations reveals that scientists from the People's Republic of China (P.R. China) are prominently represented. Possible explanations include the fact that the 2012 and 2014 international conferences pertaining to surveillance-response mechanisms were both hosted by the National Institute of Parasitic Diseases (NIPD) in Shanghai, coupled with P.R. China's growing importance with regard to the control of infectious diseases. Within 4 to 22 months of publication, three of the 22 contributions were viewed more than 10 000 times each. With sustained efforts focusing on relevant and strategic information towards control and elimination of infectious diseases, Infectious Diseases of Poverty has become a leading journal in the field of surveillance and response systems in infectious diseases and beyond

Role of the microbiome, probiotics, and 'dysbiosis therapy' in critical illness.

Purpose of reviewLoss of 'health-promoting' microbes and overgrowth of pathogenic bacteria (dysbiosis) in ICU is believed to contribute to nosocomial infections, sepsis, and organ failure (multiple organ dysfunction syndrome). This review discusses new understanding of ICU dysbiosis, new data for probiotics and fecal transplantation in ICU, and new data characterizing the ICU microbiome.Recent findingsICU dysbiosis results from many factors, including ubiquitous antibiotic use and overuse. Despite advances in antibiotic therapy, infections and mortality from often multidrug-resistant organisms (i.e., Clostridium difficile) are increasing. This raises the question of whether restoration of a healthy microbiome via probiotics or other 'dysbiosis therapies' would be an optimal alternative, or parallel treatment option, to antibiotics. Recent clinical data demonstrate probiotics can reduce ICU infections and probiotics or fecal microbial transplant (FMT) can treat Clostridium difficile. This contributes to recommendations that probiotics should be considered to prevent infection in ICU. Unfortunately, significant clinical variability limits the strength of current recommendations and further large clinical trials of probiotics and FMT are needed. Before larger trials of 'dysbiosis therapy' can be thoughtfully undertaken, further characterization of ICU dysbiosis is needed. To addressing this, we conducted an initial analysis demonstrating a rapid and marked change from a 'healthy' microbiome to an often pathogen-dominant microbiota (dysbiosis) in a broad ICU population.SummaryA growing body of evidence suggests critical illness and ubiquitous antibiotic use leads to ICU dysbiosis that is associated with increased ICU infection, sepsis, and multiple organ dysfunction syndrome. Probiotics and FMT show promise as ICU therapies for infection. We hope future-targeted therapies using microbiome signatures can be developed to correct 'illness-promoting' dysbiosis to restore a healthy microbiome post-ICU to improve patient outcomes

Characterizing the Role of Prophages on WHIB7 Expression and Antibiotic Resistance in Mycobacterium Chelonae

Mycobacterial pathogens are responsible for an ongoing public health crisis. Mycobacterium abscessus is the causative agent of lung infections that disproportionately affect immunocompromised individuals and is the most intrinsically antibiotic-resistant bacterial species known. These characteristics make M. abscessus infections difficult to treat, with a success rate of only 45%. While some extensively resistant isolates are caused by mutations in drug targets, others appear to be a result of increased intrinsic drug resistance. Common among these strains is the presence of integrated viral genomes (prophage) that are known to contribute to fitness and antibiotic resistance in other pathogens but whose roles are largely unknown in mycobacteria. M. chelonae is an opprtunisitc pathogen that is closely related to M. abscessus. We have demonstrated that the presence of an M. abscessus cluster R prophage, McProf, in M. chelonae, increased resistance to antibiotics, such as amikacin, relative to strains lacking the prophage. The presence of McProf also enhances amikacin resistance in response to sub-lethal concentrations of antibiotics, or other cellular stresses such as infection by a second phage, BPs. Relative to strains carrying only one of the prophages or no prophage, the strain carrying two prophages, BPs and McProf, had the highest amikacin resistance. This strain also showed increased expression of the transcriptional activator, whiB7, which promotes expression of intrinsic antibiotic resistance genes. We investigated the role of BPs lysogenic gene products in the presence of McProf and showed that individual expression of these genes does not contribute to whiB7 upregulation, indicating that McProf likely plays a larger role in mediating this intrinsic resistance. We identified a McProf-encoded polymorphic toxin system and evaluated its effect on whiB7 expression in M. chelonae carrying the BPs prophage. The polymorphic toxin system elevates whiB7 expression but does not fully account for the dramatic increase in expression observed in the M. chelonae strain carrying both prophages. This work suggests that prophages play a role in increasing intrinsic antibiotic resistance and stress adaptation in pathogenic mycobacteria. Given that most pathogenic mycobacteria carry one or more prophages, characterizing how prophages regulate antibiotic resistance genes and adaptation to stresses will provide insight for developing more effective therapies for mycobacterial diseases

Research opportunities on immunocompetence in space

The most significant of the available data on the effects of space flight on immunocompetences and the potential operational and clinical significance of reported changes are as follows: (1) reduced postflight blastogenic response of peripheral lymphocytes from space crew members; (2) postflight neutrophilia persisting up to 7 days; (3) gingival inflammation of the Skylab astronauts; (4) postflight lymphocytopenia, eosinopenia, and monocytopenia; (5) modifications and shifts in the microflora of space crews and spacecraft; and (6) microbial contamination of cabin air and drinking water. These responses and data disclose numerous gaps in the knowledge that is essential for an adequate understanding of space-related changes in immunocompetence

Host-linked soil viral ecology along a permafrost thaw gradient

Climate change threatens to release abundant carbon that is sequestered at high latitudes, but the constraints on microbial metabolisms that mediate the release of methane and carbon dioxide are poorly understood1,2,3,4,5,6,7. The role of viruses, which are known to affect microbial dynamics, metabolism and biogeochemistry in the oceans8,9,10, remains largely unexplored in soil. Here, we aimed to investigate how viruses influence microbial ecology and carbon metabolism in peatland soils along a permafrost thaw gradient in Sweden. We recovered 1,907 viral populations (genomes and large genome fragments) from 197 bulk soil and size-fractionated metagenomes, 58% of which were detected in metatranscriptomes and presumed to be active. In silico predictions linked 35% of the viruses to microbial host populations, highlighting likely viral predators of key carbon-cycling microorganisms, including methanogens and methanotrophs. Lineage-specific virus/host ratios varied, suggesting that viral infection dynamics may differentially impact microbial responses to a changing climate. Virus-encoded glycoside hydrolases, including an endomannanase with confirmed functional activity, indicated that viruses influence complex carbon degradation and that viral abundances were significant predictors of methane dynamics. These findings suggest that viruses may impact ecosystem function in climate-critical, terrestrial habitats and identify multiple potential viral contributions to soil carbon cycling

Experimental and computational applications of microarray technology for malaria eradication in Africa

Various mutation assisted drug resistance evolved in Plasmodium falciparum strains and insecticide resistance to female Anopheles mosquito account for major biomedical catastrophes standing against all efforts to eradicate malaria in Sub-Saharan Africa. Malaria is endemic in more than 100 countries and by far the most costly disease in terms of human health causing major losses among many African nations including Nigeria. The fight against malaria is failing and DNA microarray analysis need to keep up the pace in order to unravel the evolving parasite’s gene expression profile which is a pointer to monitoring the genes involved in malaria’s infective metabolic pathway. Huge data is generated and biologists have the challenge of extracting useful information from volumes of microarray data. Expression levels for tens of thousands of genes can be simultaneously measured in a single hybridization experiment and are collectively called a “gene expression profile”. Gene expression profiles can also be used in studying various state of malaria development in which expression profiles of different disease states at different time points are collected and compared to each other to establish a classifying scheme for purposes such as diagnosis and treatments with adequate drugs. This paper examines microarray technology and its application as supported by appropriate software tools from experimental set-up to the level of data analysis. An assessment of the level of microarray technology in Africa, its availability and techniques required for malaria eradication and effective healthcare in Nigeria and Africa in general were also underscored

Influenza Research Database: An integrated bioinformatics resource for influenza virus research

The Influenza Research Database (IRD) is a U.S. National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Bioinformatics Resource Center dedicated to providing bioinformatics support for influenza virus research. IRD facilitates the research and development of vaccines, diagnostics and therapeutics against influenza virus by providing a comprehensive collection of influenza-related data integrated from various sources, a growing suite of analysis and visualization tools for data mining and hypothesis generation, personal workbench spaces for data storage and sharing, and active user community support. Here, we describe the recent improvements in IRD including the use of cloud and high performance computing resources, analysis and visualization of user-provided sequence data with associated metadata, predictions of novel variant proteins, annotations of phenotype-associated sequence markers and their predicted phenotypic effects, hemagglutinin (HA) clade classifications, an automated tool for HA subtype numbering conversion, linkouts to disease event data and the addition of host factor and antiviral drug components. All data and tools are freely available without restriction from the IRD website at https://www.fludb.org.National Institutes of Health/National Institute for Allergy and Infectious Diseases [HHSN272201400028C]. Funding for open access charge: J. Craig Venter Institute