Table 2. Biological processes, pathways and tissue expression enrichment analysis of main clusters in asthma-signature genes list, examples of hubs, peripheral genes, super-connectors and genes present in Malacards, a gene-disease association database.
| Cluster | 1A | 1B | 2 | 3A | 3B | 3C | 4 | |
|---|---|---|---|---|---|---|---|---|
| Description | Cytokine-cytokine receptor siganling | Leukocyte transendothelial migration | Circadian rhythm | Extracellular matrix remodeling | Adherens and tight junctions | Mucus secretion | Stem cell proliferation | |
| Gene number | 239 | 114 | 15 | 282 | 19 | 8 | 82 | |
| Gene Ontology Biological Processes1 | Immune system process (GO:0002376); Defense response (GO:0006952); Immune response (GO:0006955); Chemotaxis (GO:0006935); Response to external stimulus (GO:0009605) | Immune system process (GO:0002376); Defense response (GO:0006952); Immune response (GO:0006955); Innate immune response (GO:0045087); Respiratory burst (GO:0045730) | Regulation of RNA metabolic process (GO:0051252); Regulation of transcription, DNA-dependent (GO:0006355), Heme biosynthetic process (GO:0006783), Regulation of transcription from RNA polymerase II promoter (GO:0006357), Regulation of transcription (GO:0045449) | Regulation of cell proliferation (GO:0042127); Negative regulation of apoptosis (GO:0043066); Negative regulation of programmed cell death (GO:0043069); Regulation of cell migration (GO:0030334); Regulation of cell motion (GO:0051270) | Establishment or maintenance of cell polarity (GO:0007163) | Monosaccharide metabolic process (GO:0005996); Cellular alcohol metabolic process (GO:0006066); Ventricular cardiac muscle morphogenesis (GO:0055010); Cardiac muscle contraction (GO:0060048); Carbohydrate metabolic process (GO:0005975) | Organelle organization (GO:0006996); Chromosome organization (GO:0051276); Regulation of cell cycle (GO:0051726); DNA replication (GO:0006260); DNA metabolic process (GO:0006259) | |
| KEGG Pathways1 | Cytokine cytokine receptor interaction (HSA04060); Hematopoietic cell lineage (HSA04640); Toll like receptor signaling pathway (HSA04620); Cell adhesion molecules (HSA04514); JAK STAT signaling pathway (HSA04630) | Leukocyte transendothelial migration (HSA04670); Fc epsilon ri signaling pathway (HSA04664); Phosphatidylinositol signaling system (HSA04070); Natural killer cell mediated cytotoxicity (HSA04650); Inositol phosphate metabolism (HSA00562) | Circadian rhythm (HSA04710); Glycine serine and threonine metabolism (HSA00260); Arginine and proline metabolism (HSA00330); Porphyrin and chlorophyll metabolism (HSA00860) | ECM receptor interaction (HSA04512); Focal adhesion (HSA04510); Complement and coagulation cascades (HSA04610); p53 signaling pathway (HSA04115); Arachidonic acid metabolism (HSA00590) | Tight junction (HSA04530) | Keratan sulfate biosynthesis (HSA00533); Glycan structures biosynthesis 1 (HSA01030); Olfactory transduction (HSA04740); Galactose metabolism (HSA00052) | Cell cycle (HSA04110); Purine metabolism (HSA00230); Pyrimidine metabolism (HSA00240) | |
| Human Atlas Enriched Tissues2,3 | CD33+ Myeloid cells CD19+ B cells CD14+ Monocytes Whole blood Smooth muscle | CD14+ Monocytes CD33+ Myeloid cells Whole blood Lung | CD71+ early erythoid cells Lung CD56+ NK cells CD8+ T cells CD4+ T cells | Smooth muscle Lung | Bronchial epithelial cells CD105+ Endothelial cells CD34+ cells Whole blood CD71+ early erythoid cells | Trachea CD71+ early erythoid cells CD56+ NK cells CD14+ Monocytes Lung | B lymphocytes CD105+ Endothelial cells CD71+ early erythoid cells CD34+ cells | |
| Selected genes | Hubs4 | Cd4, Il6, Stat1, Ifng, Cxcl10 | Tyrobp, Plek, Itgb2, C1qa, Slc15a3 | Alas1, Dbp, Gatm, Alas2, Nr1d1 | Vegfa, Fn1, Erbb2, Itgb1, Cav1 | Prkci, Sqstm1, Pard3, Pln, Gria1 | Muc5b, St3gal4, Clca1, Gaa, Tff2 | Mad2l1, Nme1, Pttg1, TK1, Rrm2 |
| Peripheral5 | Mtpn, Hla-dbq2 | Cotl1, Prickle1, Siglec8, Sdpr, Spon2, Clec5a | – | Tfpi2, Aqp5, Bambi, Myo1b, Efhd2, Trpan7, Mmp19, Myc, Itgb1bp2, Tmem173, Bex1 | – | Tff2, Slc26A4, Chst2 | Adam19, Cd14 | |
| Super-connectors | Nr3c1, cd4, Traf6, Rela, Stat1, Cadm1, Il1b, Cd44, Il6 | – | – | Prckd, Vwf, Erbb2 | – | – | – | |
| Malacards Asthma6 | Il13, Ccl11, Hhla-g, Il4r, Tlr6, Rnase3, Il4, Ccl17, Ccl5, Fcer2 | Pla2g7, Alox5ap, Cysltr1, Adam8 | – | Chia, Alox12, Alox15, Cat | – | – | – | |
| Percentage of genes in PubMed related to | “asthma” | 75.7% | 48.2% | 13.3% | 48.6% | 42.1% | 62.5% | 14.6% |
| “Inflammation or immunity” | 96.7% | 84.2% | 73.3% | 84.8% | 63.2% | 100.% | 56.1% | |
1Maximum of 5 enriched categories ordered by Enrichr Combined score showing an adjusted P-value < 0.05.
2Maximum of 5 tissues within a list of 17 tissues potentially found in the whole lung tissue samples in datasets under study (See
3Supplementary Figure S4 for details on Human Atlas Gene expression for all genes in each cluster).
4Top 5 hub genes ordered by Betweenness Centrality.
5Peripheral genes defined as 1-degree nodes connected to a clique.
6Malacards overlap for Asthma (119 genes, as for Sept 2014).