title: Interactive Big Data Resource to Elucidate Human Immune Pathways and Diseases.
abstract: Many functionally important interactions between genes and proteins involved in immunological diseases and processes are unknown. The exponential growth in public high-throughput data offers an opportunity to expand this knowledge. To unlock human-immunology-relevant insight contained in the global biomedical research effort, including all public high-throughput datasets, we performed immunological-pathway-focused Bayesian integration of a comprehensive, heterogeneous compendium comprising 38,088 genome-scale experiments. The distillation of this knowledge into immunological networks of functional relationships between molecular entities (ImmuNet), and tools to mine this resource, are accessible to the public at http://immunet.princeton.edu. The predictive capacity of ImmuNet, established by rigorous statistical validation, is easily accessed by experimentalists to generate data-driven hypotheses. We demonstrate the power of this approach through the identification of unique host-virus interaction responses, and we show how ImmuNet complements genetic studies by predicting disease-associated genes. ImmuNet should be widely beneficial for investigating the mechanisms of the human immune system and immunological diseases.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Gorenshteyn
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Zaslavsky
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Fribourg
authors.affiliation: New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA.
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Park
authors.affiliation: Simons Center for Data Analysis, Simons Foundation, New York, NY 10010, USA.
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Wong
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Alicja
authors.initials: A
authors.lastname: Tadych
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Boris M
authors.initials: BM
authors.lastname: Hartmann
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Departments of Pathology and Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA; Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Kleinstein
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Simons Center for Data Analysis, Simons Foundation, New York, NY 10010, USA; Department of Computer Science, Princeton University, Princeton, NJ 08540, USA. Electronic address: ogt@cs.princeton.edu.
authors.forename: Olga G
authors.initials: OG
authors.lastname: Troyanskaya
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: stuart.sealfon@mssm.edu.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Sealfon
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D019295:Computational Biology / Q000379:methods*; D053263:Gene Regulatory Networks / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000378:metabolism; D007154:Immune System Diseases / Q000235:genetics / Q000276:immunology*; D020407:Internet; D025941:Protein Interaction Mapping / Q000379:methods*; D060066:Protein Interaction Maps / Q000235:genetics / Q000276:immunology; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D060388:Support Vector Machine; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology / Q000821:virology