Revealing the acute asthma ignorome: characterization and validation of uninvestigated gene networks.
Systems biology provides opportunities to fully understand the genes and pathways in disease pathogenesis. We used literature knowledge and unbiased multiple data meta-analysis paradigms to analyze microarray datasets across different mouse strains and acute allergic asthma models. Our combined gene-driven and pathway-driven strategies generated a stringent signature list totaling 933 genes with 41% (440) asthma-annotated genes and 59% (493) ignorome genes, not previously associated with asthma. Within the list, we identified inflammation, circadian rhythm, lung-specific insult response, stem cell proliferation domains, hubs, peripheral genes, and super-connectors that link the biological domains (Il6, Il1ß, Cd4, Cd44, Stat1, Traf6, Rela, Cadm1, Nr3c1, Prkcd, Vwf, Erbb2). In conclusion, this novel bioinformatics approach will be a powerful strategy for clinical and across species data analysis that allows for the validation of experimental models and might lead to the discovery of novel mechanistic insights in asthma.
Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy.
Michela
M
Riba
Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy.
Jose Manuel
JM
Garcia Manteiga
Experimental Allergy Lab, Department of Dermatology, DIAID, Medical University of Vienna, Austria.
Berislav
B
Bošnjak
Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy.
Davide
D
Cittaro
Experimental Allergy Lab, Department of Dermatology, DIAID, Medical University of Vienna, Austria.
Pavol
P
Mikolka
Experimental Allergy Lab, Department of Dermatology, DIAID, Medical University of Vienna, Austria.
Connie
C
Le
Experimental Allergy Lab, Department of Dermatology, DIAID, Medical University of Vienna, Austria.
Michelle M
MM
Epstein
Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy.
Elia
E
Stupka
D000208:Acute Disease; D001249:Asthma / Q000235:genetics* / Q000378:metabolism*; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D015398:Signal Transduction