TABLE 4.
Functional enrichment of genes showing correlated expression in term placentas with 66 preeclampsia linked DEmiRs.
| miRNA group/ | Gene Ontology |
Pathway genes | Correlated genes in enrichment query |
Enrichment | ||
| correlation directiona | Term | Name | % | n | % n | P-valueb |
| Group 1/negativec | GO:0031012 | Extracellular matrix | 7.1% | 18 | 7.0% | 1.1 × 10–2 |
| (258 genes) | GO:0005201 | Extracellular matrix structural constituent | 10.9% | 10 | 3.9% | 4.1 × 10–2 |
| Group 2/negativec | GO:0043232 | Intracellular non-membrane-bounded organelle | 2.6% | 85 | 39.5% | 2.4 × 10–2 |
| (215 genes) | GO:0007049 | Cell cycle | 3.3% | 47 | 21.9% | 1.9 × 10–2 |
| GO:0051301 | Cell division | 5.0% | 25 | 11.6% | 3.0 × 10–3 | |
| GO:0042254 | Ribosome biogenesis | 7.1% | 19 | 8.8% | 3.8 × 10–4 | |
| GO:0000280 | Nuclear division | 6.1% | 19 | 8.8% | 4.1 × 10–3 | |
| GO:0006260 | DNA replication | 7.4% | 18 | 8.4% | 4.3 × 10–4 | |
| GO:0071103 | DNA conformation change | 8.0% | 17 | 7.9% | 3.3 × 10–4 | |
| GO:0007059 | Chromosome segregation | 6.8% | 17 | 7.9% | 3.2 × 10–3 | |
| GO:0006413 | Translational initiation | 7.7% | 14 | 6.5% | 6.4 × 10–3 | |
| GO:0044391 | Ribosomal subunit | 7.3% | 13 | 6.0% | 2.8 × 10–2 | |
| GO:0003735 | Structural constituent of ribosome | 8.5% | 13 | 6.0% | 5.2 × 10–3 | |
| GO:0022626 | Cytosolic ribosome | 11.4% | 12 | 5.6% | 5.3 × 10–4 | |
| GO:0006614 | SRP-dependent co-translational protein targeting to membrane | 12.2% | 11 | 5.1% | 8.7 × 10–4 | |
| Group 3/negative (122 genes) | GO:0006260 | DNA replication | 4.5% | 11 | 9.0% | 4.8 × 10–2 |
| Group 3/positive | GO:0042571 | Immunoglobulin complex, circulating | 100% | 5 | 0.6% | 3.2 × 10–3 |
| (825 genes) | GO:0030054 | Cell junction | 10% | 93 | 11.3% | 4.0 × 10–2 |
| Group 4/positivec | GO:0032501 | Multicellular organismal process | 4.1% | 184 | 47.5% | 5.8 × 10–4 |
| (387 genes) | GO:0044459 | Plasma membrane part | 5.4% | 88 | 22.7% | 7.5 × 10–5 |
| GO:0007399 | Nervous system development | 5.0% | 78 | 20.2% | 1.4 × 10–2 | |
| GO:0045202 | Synapse | 6.7% | 36 | 9.3% | 2.1 × 10–2 | |
| GO:0043062 | Extracellular structure organization | 8.2% | 23 | 5.9% | 4.3 × 10–2 | |
| GO:0005216 | Ion channel activity | 9.6% | 18 | 4.7% | 4.3 × 10–2 | |
| GO:0016849 | Phosphorus-oxygen lyase activity | 37.5% | 6 | 1.6% | 1.1 × 10–2 | |
| GO:0009975 | Cyclase activity | 35.3% | 6 | 1.6% | 1.7 × 10–2 | |
| Group 5/negative | GO:0005886 | Plasma membrane | 2.6% | 80 | 42.3% | 1.0 × 10–4 |
| (189 genes) | GO:0048018 | Receptor ligand activity | 8.3% | 13 | 6.9% | 1.5 × 10–3 |
| Group 5/positive | GO:0005634 | Nucleus | 18.7% | 1069 | 49.6% | 5.0 × 10–3 |
| (2155 genes) | GO:0048519 | Negative regulation of biological process | 19.5% | 726 | 33.7% | 1.9 × 10–3 |
| GO:0003676 | Nucleic acid binding | 19.9% | 645 | 29.9% | 7.8 × 10–4 | |
| GO:0002376 | Immune system process | 21.2% | 421 | 19.5% | 1.8 × 10–4 | |
| GO:0007017 | Microtubule-based process | 24.1% | 141 | 6.5% | 1.1 × 10–2 | |
| GO:0044772 | Mitotic cell cycle phase transition | 27.4% | 121 | 5.6% | 4.5 × 10–5 | |
| GO:0060271 | Cilium assembly | 28.2% | 80 | 3.7% | 3.5 × 10–3 | |
| GO:0006413 | Translational initiation | 39.2% | 71 | 3.3% | 1.7 × 10–9 | |
| GO:0003735 | Structural constituent of ribosome | 47.1% | 72 | 3.3% | 1.1 × 10–14 | |
| GO:0007059 | Chromosome segregation | 27.6% | 69 | 3.2% | 3.9 × 10–2 | |
| GO:0022626 | Cytosolic ribosome | 59.0% | 62 | 2.9% | 6.0 × 10–19 | |
| GO:0000184 | Nuclear-transcribed mRNA catabolic process, nonsense-mediated decay | 50.4% | 59 | 2.7% | 1.9 × 10–13 | |
| GO:0006614 | SRP-dependent co-translational protein targeting to membrane | 60.0% | 54 | 2.5% | 1.1 × 10–16 | |
| GO:0006261 | DNA-dependent DNA replication | 32.8% | 45 | 2.1% | 1.0 × 10–2 | |
| GO:0006334 | Nucleosome assembly | 42.3% | 44 | 2.0% | 2.5 × 10–6 | |
| GO:0048525 | Negative regulation of viral process | 40.0% | 26 | 1.2% | 2.3 × 10–2 | |
| GO:0045071 | Negative regulation of viral genome replication | 48.6% | 18 | 0.8% | 2.2 × 10–2 | |
amiRNA clusters as formed in the correlation analysis between placental miRNome and transcriptome in 40 term pregnancy samples (heatmap, Figure 5). Transcriptome data of the samples utilized for miR-Seq was derived from the published RNA-Seq dataset (Sõber et al., 2015). The number of genes entering correlation testing with the transcript level of 417 miRNAs was 16,567. Number of genes from the RNA-Seq dataset showing correlated expression with the specific miRNA Group are indicated in brackets. Full details are presented in Supplementary Tables 27–32. bP-value corrected for multiple testing by g: SCS method (Reimand et al., 2007). cNo functional enrichment pathways were identified for genes showing positive expressional correlation with miRNAs in Groups 1 and 2, and genes showing negative correlation in Group 4.