Open Access Highly Accessed Research article

Integrated network analysis reveals a novel role for the cell cycle in 2009 pandemic influenza virus-induced inflammation in macaque lungs

Jason E Shoemaker1, Satoshi Fukuyama1, Amie J Eisfeld2, Yukiko Muramoto3, Shinji Watanabe12, Tokiko Watanabe12, Yukiko Matsuoka124, Hiroaki Kitano14567* and Yoshihiro Kawaoka12389*

Author Affiliations

1 ERATO Infection-Induced Host Responses Project, Saitama, 332-0012, Japan

2 School of Veterinary Medicine, Department of Pathobiological Sciences, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, USA

3 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan

4 The Systems Biology Institute, Tokyo, Japan

5 Division of Systems Biology, Cancer Institute, Tokyo, Japan

6 Sony Computer Science Laboratories, Inc, Tokyo, Japan

7 Okinawa Institute of Science and Technology, Okinawa, Japan

8 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan

9 International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan

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BMC Systems Biology 2012, 6:117  doi:10.1186/1752-0509-6-117

Published: 31 August 2012

Additional files

Additional file 1:

Summary of the number of probes DE and the number of DE probes which are chemokine ligands and receptors (CCL/R), interleukins (IL) or interferon stimulated genes for each day. Numbers in parenthesis show the number of up (left) and down regulated genes (right). We also show the number of genes DE on both days (intersection).

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Additional file 2:

All genes found differentially expressed on day 3 or 7 post infection.

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Additional file 3:

Microarray data description file. File describes: from which lobe the RNA was isolated; which virus the animal was infected with; the day the sample was collected; the severity of the lesions from which the sample was isolated, and the amount of virus isolated from the region.

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Additional file 4:

Work Book Explanation: all genes lists were separated into up- or down-regulated when comparing CA04-infected tissue to KUTK4-infected. DE gene's Genbank Accession IDs were uploaded into Ingenuity and the benjamini hochberg corrected P-value was used to quantify enrichment.

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Additional file 5:

Work Book Explanation: all genes lists were separated into up- or down-regulated when comparing CA04-infected tissue to KUTK4-infected. DE gene's Genbank Accession IDs were uploaded into DAVID and the benjamini hochberg corrected P-value was used to quantify enrichment.

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Additional file 6:

Work Book Explanation: cell specific gene ontology enrichment. All genes lists were separated into up- or down-regulated when comparing CA04-infected tissue to KUTK4-infected. DE gene's Genbank Accession ID was uploaded into Ingenuity and the benjamini hochberg corrected P-value was used to quantify enrichment. Here we report all categories with a FDR adjusted P-value < 0.05.

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Additional file 7:

Cell-specific CA04-induced functional enrichment on day 3 PI. This is an enlarged illustration of Figure 3A which provides information on the specific function of each enriched IPA annotation.

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Additional file 8:

Cell-specific CA04-induced functional enrichment on day 7 PI. This is an enlarged illustration of Figure 3B which provides information on the specific function of each enriched IPA annotation.

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Additional file 9:

The subnetwork of the human PPI which contains 70 proteins whose transcripts were significantly expressed in CA04-infected tissue. This network was identified using IPA. Up-regulated genes are colored red while down-regulated genes are colored green.

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Additional file 10:

The "Role of Cytokines in Mediating Communication between Immune Cells" Pathway from the IPA database. Proteins colored red were identified as upregulated in CA04-infected tissue. Interactions which promote protein production or cell proliferation are illustrates with arrows. Inhibitory interactions are illustrated with ┴.

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Additional file 11:

The "Role of CHK Proteins in Cell Cycle" Pathway from the IPA database. Proteins colored red were identified as upregulated in CA04-infected tissue. Interactions which promote protein production or cell proliferation are illustrates with arrows. Inhibitory interactions are illustrated with ┴. Interactions which promote a particular phenotype (e.g., G2/S arrest) are illustrated with lines ending in a circle.

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Additional file 12:

Work Book Explanation: enriched canonical biological pathways for genes differentially expressed between CA04 and KUTK4 infections.

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Additional file 13:

Work Book Explanation: official names, symbols and accession numbers of all proteins shown in Figure 5.

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