Table 3.
Gene Cluster Molecular and Biological Enrichment Characteristics
| GC (n) | High (SCs) | Int (SCs) | Low (SCs) | Functional Pathway/Cellular Association | Genes |
|---|---|---|---|---|---|
| 1 (131) | 1 | 3, 4, 5 | 2 | Innate immunity/antibacterial function | BPIFA1, MUC5B, PGLYPR4, NOX1 |
| Cell proliferation/apoptosis | ERBB2, S1PR, IL36RN | ||||
| Lymphocyte activation/migration | LAG3, CCL15, SLAMF7, SLAMF9, MALL, TNFSF4 | ||||
| Other | HCRT, FGF family | ||||
| 2 (172) | 4 | 1, 5 | 2, 3 | Cilia structure/function | DNAH1, DNAH3, IFT122, DNAI1, FBF1, TMEM231, BBS1, ARL3, IFT140, HYDIN, KIF19, DNAH10 |
| Other | CRY2, INSR, SCGB1A1 and 3A1, SMAD3, DTX3, TMEM8B, ATXN2 | ||||
| 3 (52) | 4, 3 | 2 | 1, 5 | TNF-α | SPPL2B, MAPK4K4, IKBKB |
| Muscle | DMPK. POPDC2, MUSTN1, TNNI3, FERL5, MYO15B | ||||
| 4 (325) | 1 | 4, 5 | 2, 3 | Notch signaling/cell adhesion | WNK4, JAG2, EPDR1, CD302, CDON, GXYLT2, HEY2, THBS4, RBPJ, CLDN16, OSBPL3, GJB7, CDH1 |
| Neuronal function | SHANK2, LRP8, KCNN3, MAOB, SEMA3E, LMO3, EFHD1, NDN, CHN1, NPAS3, NDNF, NAV3, SLITRK5, SLC6A16, SNCAIP, TUB, INA, MAPT, ORS1E1, SCSK1, EFNB2, PMMA3, CLU, STXBP1, ENO2, OPRL1, DDC | ||||
| Dystrophin family | SNTB1, SGCE, SSPN, CNTD1 | ||||
| WNT family | WIF1, WNT5B, RHOU, ASCDD1, DKK3 | ||||
| Ion channels | KCNA1, KCNC1, CACNB1, CACNA202, SCN3A, NEDD4L | ||||
| Other | BPHLHE31, PER2, IL5RA, GSTA1, 2, 3, 5, HNMT, GAB2, PIAS1, FOXA2, LTF | ||||
| 5 (50) | 1, 5 | 2, 4 | 3 | No obvious functional/cellular associations “Interesting genes” | PFDN5, KCNMB2, BTK, TNFSF12, GPAN |
| 6 (150) | 2, 3 | 4,5 | 1 | Microtubules (2%) | TUBA4A, ACOT13, CKAP2 |
| Mitochondrial (3%) | ATP5H, MTERF, ETFA, NNT, CPT1A. CYCS | ||||
| Actin related (2%) | LIMA1, PDF1B, ACTR3, TMP4 | ||||
| Neuronal (2%) | BDNF, GRIK2, NAV1, RIT1 | ||||
| Other | IRAK4, GART, GMP5, SMAP1, ADAM9, IBTK, ITGB6, CXCL14 | ||||
| 7 (228) | 2, 3 | 4 | 1, 5 | Interferons (type 1 and 2) (∼2%) | DUOX2, MX2, IL18R1, NOS2 |
| Apoptosis (∼3%) | CARD14, TRADD, CASP6, TXNDC5, AK2, TNFRFS18, MAGED1 | ||||
| P38 related | MAPK13, MAP2K6 | ||||
| Keratins | KRT23, KRT6A, KRT18 | ||||
| Sialyl Lewis antigen | FUT3, 5, 6 | ||||
| Cell matrix interactions (∼3.5%) | DIAPH3, LGALS7, LGALS7B, FERMT1, LOXL4, RHOC, LOX, TNC | ||||
| Other | IRAK3, TEP and TIMELESS, PTK6, MUC4, DEFB1, PLA2G4A and ABCC1, LRRC8A, ICA1, POP1 | ||||
| 8 (96) | 2, 5 | 1, 3, 4 | Cysteine metabolism (4%) | CCBL1, CST1, CST2, FETUB | |
| Mucins (5%) | MUC5AC, TFF3, TFF2, FOXA3, GANLT12 | ||||
| Mast cells (11%) | HPGDS, PTGS1, P2RY14, CTSG, HDC, IL1RL1, KIT, CPA3, TPSAB1, MS4A2, TPSD1, CD22/SIGLEC2, SIGLEC17P, SLC18A2, DPP4 | ||||
| Vasoconstrictors (possibly MC) (3%) | UTS2, P3RX1 | ||||
| Glycolipid antigen presentation | CD1C, CD1E | ||||
| Other | PTGDR2, MYO1C, CNRIP1, PRB1, 2 and 4 | ||||
| 9 (180) | 2 | 3, 4, 5 | 1 | Mitochondria (3%) | MTHFD2, MRPL15, COX17, ATP5O, PYCR1, HK2 |
| Intracellular trafficking (5%) | STKBP5, RAB27B, TBC1D15, S100A6. ARL1, KIF16B, SYTL4, SEC24D, SEC22A | ||||
| O-linked glycosylation (2%) | GALNT1, 4, 7, 10 | ||||
| N-linked glycosylation (2%) | MAGT1, FUT8, ALG5, ERLEC1 | ||||
| “Type 2 genes” (2%) | ALOX15A, CCL26, SERPINB2, POSTN | ||||
| Other | BCL2L14, RIPK2, CORO1C, ARNTL2, MUC2, MGST2, NTRK2, CD44 |
Definition of abbreviations: GC = gene cluster; Int = intermediate; SCs = subject clusters; TNF = tumor necrosis factor.
Genes differentially expressed to a P value of P < 10−6 between at least two of the five SCs were added to the FeNO-correlated genes to form a highly differentiating set of genes. Complete linkage hierarchical clustering of this gene set formed nine GCs. This table details important genes with associated functional pathways and/or cellular associations in each of these GCs. The columns “High,” “Int,” and “Low” indicate comparative expression levels.