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Principal Investigator: CHRISTIAN FORST
Organization: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Fiscal Year: 2021
Award: $211,875
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
Emergent viral infections, such as SARS-CoV-2 and new influenza strains, pose an enormous health and economic burden on patients and the society. Viral cycles between the animal reservoir and the human population cause millions of hospitalizations and thousands of deaths each year, especially in high-risk groups, such as elderly, pregnant women, obese individuals with a compromised immune system, and indigenous populations. Disease morbidity and mortality increase after interspecies transmission of a new viral strain, and becomes capable of infecting humans. In this case, there is no (or minimal) pre-existing antibody-mediated immunity to the new viral strain at the population level, leading to millions of infections and, ultimately, a pandemic. In the absence of antibodies, the severity of the disease can be ameliorated by broadly cross-reactive cellular immunity. However, the precise mechanism of how immune cells mediate recovery in some individuals, but not others, is far from clear. Fortunately, a diverse and rich collection of publically available datasets can be leveraged to thoroughly investigate the specific molecular mechanisms of viral infection and host response. Gene expression profiles from human cohorts and animal studies in GEO/SRA, immunological profiles in ImmPort or viral strain data, and interaction with immune epitopes in the Influenza Research Database (IRD) or the Virus Pathogen Database and Analysis Resource (ViPR), both Bioinformatics Resource Centers (BRC) of NIAID, are examples of such resources. In particular, high-resolution single-cell RNA-seq data enables us to study relevant processes during influenza and SARS-CoV-2 infections in greater detail. The overarching hypothesis of our proposed work is that diversity in virus strains, genetic immune epitopes, and responding immune cells contributes to heterogeneous outcomes of viral infection. By integrating all existing large-scale single-cell and bulk transcriptomic data in SARS-CoV-2 and influenza infections, we aim to identify determinants of viral infections and key processes underlying viral replication, and immune response using integrative multi-scale network biology approaches. The proposed research highlights the importance of identifying relevant key-immune processes at a single-cell resolution that control the infection and limit the extent of inflammatory damage. Such findings will significantly improve therapeutic options in the fight against these threatening infectious diseases. All the models and the software tools developed through this project will be shared with the community.
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disease rate><NIAID><National Institute of Allergy and Infectious Disease><Native People><Native-Born><Network Analysis><Outcome><Pathway Analysis><Pathway interactions><Patients><Pb element><Physiologic><Physiological><Population><Pregnant Women><Prevention><Process><Proteomics><Public Health><Recovery><Research><Research Resources><Resolution><Resources><Risk><SARS corona virus 2><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV2><SARS-CoV2 epidemic><SARS-CoV2 infection><SARS-CoV2 pandemic><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Severities><Severity of illness><Signal Pathway><Societies><Software Tools><Therapeutic><Validation><Viral><Viral Diseases><Viral Gene Products><Viral Gene Proteins><Viral Proteins><Virulent><Virus><Virus Diseases><Virus Replication><Work><Wuhan coronavirus><advanced age><allergic/immunologic body system><allergic/immunologic organ system><anti-viral agents><anti-viral drugs><anti-virals><antibody-mediated immunity><bio-informatics resource><bioinformatics resource><cohort><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><cross reactivity><cross-species spillover><cross-species transmission><data base><disease severity><elders><expectant mother><expecting mother><fight against><flu infection><flu serotype><flu strain><flu subtype><flu viral strain><flu virus infection><flu virus strain><geriatric><hCoV19><health economics><heavy metal Pb><heavy metal lead><high dimensionality><high risk group><high risk population><host jump><host response><host switching><immune system response><immunoresponse><improved><in silico><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with flu><infected with flu virus><infected with influenza><infected with influenza virus><infected with severe acute respiratory syndrome coronavirus 2><influenza epidemic><influenza infection><influenza serotype><influenza strain><influenza subtype><influenza viral strain><influenza virus infection><influenza virus strain><influenzavirus><interspecies transmission><late life><later life><mortality><multiomics><multiple omics><nCoV2><obese individuals><obese people><obese person><obese population><obese subjects><older adult><older person><pandemic><pandemic disease><pathogenic virus><pathway><personalization of treatment><personalized medicine><personalized therapy><personalized treatment><pregnant mothers><programs><response><scRNA-seq><scaffold><scaffolding><senior citizen><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><single cell RNA-seq><single cell RNAseq><single cell analysis><single cell sequencing><single-cell RNA sequencing><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapeutic target><transcriptomics><transmission across species><transmission between species><transmitted across species><transmitted between species><transmitted cross-species><viral infection><viral infection mechanism><viral multiplication><viral pathogen><viral replication><virus infection><virus infection mechanism><virus multiplication><virus pathogen><virus protein><virus-induced disease><youngster>