scholarly journals Preprocessing of Public RNA-Sequencing Datasets to Facilitate Downstream Analyses of Human Diseases

Data ◽  
2021 ◽  
Vol 6 (7) ◽  
pp. 75
Author(s):  
Naomi Rapier-Sharman ◽  
John Krapohl ◽  
Ethan J. Beausoleil ◽  
Kennedy T. L. Gifford ◽  
Benjamin R. Hinatsu ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Rna Sequencing ◽  
Lupus Erythematosus ◽  
Intracellular Signaling ◽  
Influenza A ◽  
Lymphoblastic Leukemia ◽  
Transcriptional Response ◽  
Chronic Obstructive ◽  
Intracellular Signaling Pathway ◽  
Syncytial Virus

Publicly available RNA-sequencing (RNA-seq) data are a rich resource for elucidating the mechanisms of human disease; however, preprocessing these data requires considerable bioinformatic expertise and computational infrastructure. Analyzing multiple datasets with a consistent computational workflow increases the accuracy of downstream meta-analyses. This collection of datasets represents the human intracellular transcriptional response to disorders and diseases such as acute lymphoblastic leukemia (ALL), B-cell lymphomas, chronic obstructive pulmonary disease (COPD), colorectal cancer, lupus erythematosus; as well as infection with pathogens including Borrelia burgdorferi, hantavirus, influenza A virus, Middle East respiratory syndrome coronavirus (MERS-CoV), Streptococcus pneumoniae, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We calculated the statistically significant differentially expressed genes and Gene Ontology terms for all datasets. In addition, a subset of the datasets also includes results from splice variant analyses, intracellular signaling pathway enrichments as well as read mapping and quantification. All analyses were performed using well-established algorithms and are provided to facilitate future data mining activities, wet lab studies, and to accelerate collaboration and discovery.

scholarly journals A case of SLE with COVID-19 and multiple infections

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 1054-1060
Author(s):  
Ruoqi Ning ◽  
Silu Meng ◽  
Fangxu Tang ◽  
Chong Yu ◽  
Dong Xu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Severe Acute Respiratory Syndrome ◽  
Lupus Erythematosus ◽  
Influenza A ◽  
Immunosuppressive Drugs ◽  
Multiple Infections ◽  
Systemic Lupus ◽  
Suspected Infection ◽  
Global Pandemic ◽  
Chronic Use

AbstractThe coronavirus disease 2019 (COVID-19) has become a global pandemic, which is induced by infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with systemic lupus erythematosus (SLE) are susceptible to infections due to the chronic use of immunosuppressive drugs and the autoimmune disorders. Now we report a case of SLE infected with SARS-CoV-2, influenza A virus and Mycoplasma pneumoniae concurrently. The patient used hydroxychloroquine and prednisone chronically to control the SLE. After infection of SARS-CoV-2, she was given higher dose of prednisone than before and the same dosage of hydroxychloroquine. Besides, some empirical treatments such as antiviral, antibiotic and immunity regulating therapies were also given. The patient finally recovered from COVID-19. This case indicated that hydroxychloroquine may not be able to fully protect SLE patient form SARS-CoV-2. Intravenous immunoglobulin therapies and increased dose of corticosteroids might be adoptable for patient with both COVID-19 and SLE. Physicians should consider SARS-CoV-2 virus test when SLE patient presented with suspected infection or SLE flare under the epidemic of COVID-19.

scholarly journals Akt Inhibitor Akt-IV Blocks Virus Replication through an Akt-Independent Mechanism

2009 ◽  
Vol 83 (22) ◽  
pp. 11665-11672 ◽  
Author(s):  
Ewan F. Dunn ◽  
Rachel Fearns ◽  
John H. Connor
Keyword(s):  
Signaling Pathway ◽  
Virus Replication ◽  
Intracellular Signaling ◽  
Akt Pathway ◽  
Akt Inhibitor ◽  
Antiviral Compound ◽  
Intracellular Signaling Pathway ◽  
Cytopathic Effects ◽  
Syncytial Virus

ABSTRACT Many viruses activate the phosphatidylinositol 3′-kinase (PI3k)/Akt intracellular signaling pathway to promote viral replication. We have analyzed whether a rapidly replicating rhabdovirus, vesicular stomatitis virus (VSV), requires the PI3k/Akt signaling pathway for its replication. Through the use of chemical inhibitors of PI3k and Akt, we show that VSV replication and cytopathic effects do not require activation of these kinases. Inhibitors that block the activating phosphorylations of Akt at threonine 308 (Thr308) and serine 473 (Ser473) did not inhibit VSV protein expression or the induction of the cytopathic effects of VSV. One compound, Akt inhibitor Akt-IV, inhibited the replication of VSV, respiratory syncytial virus, and vaccinia virus but increased the phosphorylation of Akt at positions Thr308 and Ser473 and did not inhibit Akt kinase activity in vitro. Together, our data suggest that the PI3k/Akt pathway is of limited relevance to the replication of VSV but that Akt inhibitor Akt-IV is a novel broad-spectrum antiviral compound with a mechanism differing from that of its previously reported effect on the PI3k/Akt pathway. Identification of other targets for this compound may define a new approach for blocking virus replication.

scholarly journals SP-A and SP-D: Dual Functioning Immune Molecules With Antiviral and Immunomodulatory Properties

2021 ◽  
Vol 11 ◽  
Author(s):  
Alastair Watson ◽  
Jens Madsen ◽  
Howard William Clark
Keyword(s):  
Viral Infection ◽  
Influenza A ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Chronic Obstructive ◽  
Cell Functions ◽  
Increased Risk ◽  
Syncytial Virus

Surfactant proteins A (SP-A) and D (SP-D) are soluble innate immune molecules which maintain lung homeostasis through their dual roles as anti-infectious and immunomodulatory agents. SP-A and SP-D bind numerous viruses including influenza A virus, respiratory syncytial virus (RSV) and human immunodeficiency virus (HIV), enhancing their clearance from mucosal points of entry and modulating the inflammatory response. They also have diverse roles in mediating innate and adaptive cell functions and in clearing apoptotic cells, allergens and other noxious particles. Here, we review how the properties of these first line defense molecules modulate inflammatory responses, as well as host-mediated immunopathology in response to viral infections. Since SP-A and SP-D are known to offer protection from viral and other infections, if their levels are decreased in some disease states as they are in severe asthma and chronic obstructive pulmonary disease (COPD), this may confer an increased risk of viral infection and exacerbations of disease. Recombinant molecules of SP-A and SP-D could be useful in both blocking respiratory viral infection while also modulating the immune system to prevent excessive inflammatory responses seen in, for example, RSV or coronavirus disease 2019 (COVID-19). Recombinant SP-A and SP-D could have therapeutic potential in neutralizing both current and future strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus as well as modulating the inflammation-mediated pathology associated with COVID-19. A recombinant fragment of human (rfh)SP-D has recently been shown to neutralize SARS-CoV-2. Further work investigating the potential therapeutic role of SP-A and SP-D in COVID-19 and other infectious and inflammatory diseases is indicated.

scholarly journals A signaling pathway-driven bioinformatics pipeline for predicting therapeutics against emerging infectious diseases

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 330
Author(s):  
Tiana M. Scott ◽  
Sam Jensen ◽  
Brett E. Pickett
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Infectious Diseases ◽  
Influenza A ◽  
Meta Analysis ◽  
Emerging Infectious Diseases ◽  
Infectious Agent ◽  
Sequencing Data ◽  
Bioinformatics Pipeline ◽  
Syncytial Virus ◽  
Approved Drugs

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of coronavirus disease-2019 (COVID-19), is a novel Betacoronavirus that was first reported in Wuhan, China in December of 2019. The virus has since caused a worldwide pandemic that highlights the need to quickly identify potential prophylactic or therapeutic treatments that can reduce the signs, symptoms, and/or spread of disease when dealing with a novel infectious agent. To combat this problem, we constructed a computational pipeline that uniquely combines existing tools to predict drugs and biologics that could be repurposed to combat an emerging pathogen. Methods: Our workflow analyzes RNA-sequencing data to determine differentially expressed genes, enriched Gene Ontology (GO) terms, and dysregulated pathways in infected cells, which can then be used to identify US Food and Drug Administration (FDA)-approved drugs that target human proteins within these pathways. We used this pipeline to perform a meta-analysis of RNA-seq data from cells infected with three Betacoronavirus species including severe acute respiratory syndrome coronavirus (SARS-CoV; SARS), Middle East respiratory syndrome coronavirus (MERS-CoV; MERS), and SARS-CoV-2, as well as respiratory syncytial virus and influenza A virus to identify therapeutics that could be used to treat COVID-19.  Results: This analysis identified twelve existing drugs, most of which already have FDA-approval, that are predicted to counter the effects of SARS-CoV-2 infection. These results were cross-referenced with interventional clinical trials and other studies in the literature to identify drugs on our list that had previously been identified or used as treatments for COIVD-19 including canakinumab, anakinra, tocilizumab, sarilumab, and baricitinib. Conclusions: While the results reported here are specific to Betacoronaviruses, such as SARS-CoV-2, our bioinformatics pipeline can be used to quickly identify candidate therapeutics for future emerging infectious diseases.

scholarly journals A signaling pathway-driven bioinformatics pipeline for predicting therapeutics against emerging infectious diseases

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 330
Author(s):  
Tiana M. Scott ◽  
Sam Jensen ◽  
Brett E. Pickett
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Infectious Diseases ◽  
Influenza A ◽  
Meta Analysis ◽  
Emerging Infectious Diseases ◽  
Infectious Agent ◽  
Sequencing Data ◽  
Bioinformatics Pipeline ◽  
Syncytial Virus ◽  
Approved Drugs

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of coronavirus disease-2019 (COVID-19), is a novel Betacoronavirus that was first reported in Wuhan, China in December of 2019. The virus has since caused a worldwide pandemic that highlights the need to quickly identify potential prophylactic or therapeutic treatments that can reduce the signs, symptoms, and/or spread of disease when dealing with a novel infectious agent. To combat this problem, we constructed a computational pipeline that uniquely combines existing tools to predict drugs and biologics that could be repurposed to combat an emerging pathogen. Methods: Our workflow analyzes RNA-sequencing data to determine differentially expressed genes, enriched Gene Ontology (GO) terms, and dysregulated pathways in infected cells, which can then be used to identify US Food and Drug Administration (FDA)-approved drugs that target human proteins within these pathways. We used this pipeline to perform a meta-analysis of RNA-seq data from cells infected with three Betacoronavirus species including severe acute respiratory syndrome coronavirus (SARS-CoV; SARS), Middle East respiratory syndrome coronavirus (MERS-CoV; MERS), and SARS-CoV-2, as well as respiratory syncytial virus and influenza A virus to identify therapeutics that could be used to treat COVID-19.  Results: This analysis identified twelve existing drugs, most of which already have FDA-approval, that are predicted to counter the effects of SARS-CoV-2 infection. These results were cross-referenced with interventional clinical trials and other studies in the literature to identify drugs on our list that had previously been identified or used as treatments for COIVD-19 including canakinumab, anakinra, tocilizumab, sarilumab, and baricitinib. Conclusions: While the results reported here are specific to Betacoronaviruses, such as SARS-CoV-2, our bioinformatics pipeline can be used to quickly identify candidate therapeutics for future emerging infectious diseases.

Novel New Drug Approvals in 2011: A Succinct Analysis of Drug Discovery Trends in the United States

2012 ◽  
Vol 5 (2) ◽  
pp. 1661-1665
Author(s):  
D Samba Reddy
Keyword(s):  
United States ◽  
Drug Discovery ◽  
Lupus Erythematosus ◽  
Lymphoblastic Leukemia ◽  
The United States ◽  
New Drugs ◽  
Chronic Obstructive ◽  
The Past ◽  
New Drug ◽  
Drug Approvals

Thirty (30) new drugs have been approved by the FDA in 2011 for marketing in the United States. This list includes novel new drugs, known as new molecular entities (NMEs), biologics and new indications for drugs already approved. Eleven of the 30 NMEs were new drugs approved for orphan diseases, while twelve are considered first-in-class drugs with a unique new mechanism of action. During 2011, the FDA approved many unique and new drugs for chronic obstructive pulmonary disease, deep vein thrombosis, systemic lupus erythematosus (SLE), and epilepsy. In addition,  several new biologicals were approved in the past year for the treatment of macular degeneration, acute lymphoblastic leukemia, Hodgkin lymphoma, melanoma, chronic hepatitis C, and SLE. The introduction of 30 NMEs in 2011 underscores a robust success rate. It confirms that innovation is once again beginning to pay off. Analysis of drug approvals reveals a unique new trend in drug discovery in the face of stiff competition from generic products and declining revenues. In the existing climate of reduced pipeline for NMEs, the future and survival of big companies rests heavily on their unique niche products and biologics with relatively less competition from generic manufacturers. However, the competition for biosimilars is growing by the hour and therefore, crafting innovative generic biologicals is vital for generic biotech companies. Although the number of NMEs approved in the past 10 years has been declining, there is a substantial increase in R&D expenditure for drug discovery. Overall, the new drug approval list unveils unique and emerging trends in drug discovery especially in the current generics era. 

Bacteria and Viral Profile of Severe Acute Respiratory Infections of Children Attending Yangon Children’s Hospital and Yankin Children’s Hospital

2019 ◽  
Vol 31 (1) ◽  
pp. 44-51
Keyword(s):  
Influenza A ◽  
Respiratory Infections ◽  
Antibiotic Sensitivity ◽  
Parainfluenza Virus ◽  
Sensitivity Testing ◽  
E Coli ◽  
Children's Hospital ◽  
Severe Acute Respiratory Infection ◽  
Children’S Hospital ◽  
Syncytial Virus

Objectives of study are (1) to reinforce the national capacity for diagnosis and antibiogram of some infectious diseases causing severe acute respiratory infection (SARI) and (2) to build a network between hospital and laboratory for the diagnosis and surveillance of SARI in Yangon. This study is a crosssectional hospital- and laboratory-based descriptive study. A total of 825 samples including respiratory samples and blood samples from 511 children attending Yangon Children’s Hospital and Yankin Children’s Hospital from December 2014 to April 2016 for treatment of SARI were included. Identification and antibiotic sensitivity testing were done using Vitek 2. Out of 129 gram-negative bacilli (GNB), K. pneumoniae 32%, P. aeruginosa 18%, A. baumannii 13%, E. coli 9% were mostly isolated. Among 35 gram-positive cocci (GPC), S. aureus 42% and S. pneumoniae 6% were mostly isolated. Multidrug resistance rates were E. coli 100%, K. pneumoniae 95%, A. baumanii 82% and P. aeruginosa 17%. Extended-spectrum beta-latamase (ESBL)-producing K. pneumoniae and E. coli was 6 out of 10 tested organisms. Carbarpenemase-producing GNB and methicillin-resistant Staphylococcus aureus (MRSA) were 21% and 33%, respectively. Virology section tested 529 samples of 490 patients using the FTD33 Multiplex PCR method which can detect 33 pathogens including 20 viruses, 12 bacteria and 1 fungus. Out of 490 patients, 374 were PCR positive. Different types of samples including nasopharyngeal, throat, endotracheal and laryngeal swab, tracheal secretion and bronchoalveolar lavage, were tested. Out of 566 viruses, respiratory syncytial virus (RSV) (19.3%), rhinovirus (17.0%), parechovirus (14.3%), bocavirus (11.1%), adenovirus (10.2%), metapneumo-virus A and B (10.2%), parainfluenza virus (5.7%), enterovirus (3.0%), influenza A virus (2.8%), coronavirus (4%), parainfluenza virus (0.9%) and influenza C virus (0.4%) were detected. This study highlighted the etiological agents of bacteria, viruses and drug-resistant bacterial pathogens in SARI.

THE ROLE OF PHOSPHATIDYLINOSITOL-3-KINASE IN CARCINOGENESIS

2017 ◽  
Vol 63 (4) ◽  
pp. 545-556
Author(s):  
Natalya Oskina ◽  
Aleksandr Shcherbakov ◽  
Maksim Filipenko ◽  
Nikolay Kushlinskiy ◽  
L. Ovchinnikova
Keyword(s):  
Genetic Disease ◽  
Intracellular Signaling ◽  
Somatic Mutations ◽  
Pi3k Pathway ◽  
Genetic Alterations ◽  
Phosphatidylinositol 3 Kinase ◽  
Intracellular Signaling Pathway ◽  
Metabolic Activities ◽  
Carcinogenic Process

Currently it is established that cancer is a genetic disease and that somatic mutations are the initiators of the carcinogenic process. The PI3K/AKT/mTOR pathway is an important intracellular signaling pathway regulating the cell growth and metabolic activities. Aberrant activation of the PI3K pathway is commonly observed in many different cancers. In this review we analyze the genetic alterations of PI3K pathway in a variety of human malignancies and discuss their possible implications for diagnosis and therapy.

scholarly journals PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects

2021 ◽  
Vol 22 (7) ◽  
pp. 3464
Author(s):  
Rosalin Mishra ◽  
Hima Patel ◽  
Samar Alanazi ◽  
Mary Kate Kilroy ◽  
Joan T. Garrett
Keyword(s):  
Clinical Trials ◽  
Intracellular Signaling ◽  
Pi3k Pathway ◽  
Combination Therapies ◽  
Intracellular Signaling Pathway ◽  
Pi3k Inhibitors ◽  
Promising Therapeutic Target ◽  
Cancer Cell Survival ◽  
Current Therapies ◽  
Cancer Types

The phospatidylinositol-3 kinase (PI3K) pathway is a crucial intracellular signaling pathway which is mutated or amplified in a wide variety of cancers including breast, gastric, ovarian, colorectal, prostate, glioblastoma and endometrial cancers. PI3K signaling plays an important role in cancer cell survival, angiogenesis and metastasis, making it a promising therapeutic target. There are several ongoing and completed clinical trials involving PI3K inhibitors (pan, isoform-specific and dual PI3K/mTOR) with the goal to find efficient PI3K inhibitors that could overcome resistance to current therapies. This review focuses on the current landscape of various PI3K inhibitors either as monotherapy or in combination therapies and the treatment outcomes involved in various phases of clinical trials in different cancer types. There is a discussion of the drug-related toxicities, challenges associated with these PI3K inhibitors and the adverse events leading to treatment failure. In addition, novel PI3K drugs that have potential to be translated in the clinic are highlighted.

scholarly journals Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 234
Author(s):  
Sarah Al-Beltagi ◽  
Cristian Alexandru Preda ◽  
Leah V. Goulding ◽  
Joe James ◽  
Juan Pu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Influenza A Virus ◽  
Broad Spectrum ◽  
Influenza A ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Virus Challenge ◽  
2009 H1n1 ◽  
Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

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