Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses

Irina Nudelman, Daniil Kudrin, German Nudelman, Raamesh Deshpande, Boris M. Hartmann, Steven H. Kleinstein, Chad L. Myers, Stuart C. Sealfon, Elena Zaslavsky

Research output: Contribution to journalArticlepeer-review

Abstract

Influenza is a serious global health threat that shows varying pathogenicity among different virus strains. Understanding similarities and differences among activated functional pathways in the host responses can help elucidate therapeutic targets responsible for pathogenesis. To compare the types and timing of functional modules activated in host cells by four influenza viruses of varying pathogenicity, we developed a new DYNAmic MOdule (DYNAMO) method that addresses the need to compare functional module utilization over time. This integrative approach overlays whole genome time series expression data onto an immune-specific functional network, and extracts conserved modules exhibiting either different temporal patterns or overall transcriptional activity. We identified a common core response to influenza virus infection that is temporally shifted for different viruses. We also identified differentially regulated functional modules that reveal unique elements of responses to different virus strains. Our work highlights the usefulness of combining time series gene expression data with a functional interaction map to capture temporal dynamics of the same cellular pathways under different conditions. Our results help elucidate conservation of the immune response both globally and at a granular level, and provide mechanistic insight into the differences in the host response to infection by influenza strains of varying pathogenicity.

Original languageEnglish (US)
Article number691758
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - Jul 14 2021

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health contract HHSN272201000054C and Grant 1U19AI117873. IN was supported by the Graduate School of Arts and Science, New York University.

Publisher Copyright:
© Copyright © 2021 Nudelman, Kudrin, Nudelman, Deshpande, Hartmann, Kleinstein, Myers, Sealfon and Zaslavsky.

Keywords

  • Influenza H1N1
  • conserved and differential modules
  • differential regulation
  • functional network
  • module discovery
  • temporal dynamics
  • transcriptional profile
  • virus infection

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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