Table 2.
Overlap of PMS differentially expressed genes (FDR < 5%) with other ASD iPSC transcriptome studies
| Study description | hiPSC-NPCs | hiPSC-neurons | Enriched GO terms | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Author and year | Target gene | Approach | Cellular model | FET P-value | Odds ratio | Intersect | Example genes | FET P-value | Odds ratio | Intersect | Example genes | |
| Huang et. 2019 | SHANK3 | shRNA KD | hiPSC-derived neurons | 3.3E-04 | 1.93 | 44 | COL5A2, COL18A1NDP, ADAMTS18, CRTAP, NFATC1 | 2.4E-07 | 4.64 | 20 | WNT3A, BCAN, FRZB, SPO3, APCDD1, WNT7B | Canonical Wnt signaling, perinuclear endoplasmic reticulum lumen |
| Wang et. 2015 | CHD8 | CRISPR/Cas9 heterozygous KO | hiPSC-derived NPCs | 4.0E-03 | 1.71 | 33 | CCCND1, VCAN, NFATC1, SMAD9, LRRC8B, HOXB5 | 1.8E-05 | 4.14 | 15 | FRZB, FREM1, RSPO3, ROR2, MMP15, WNT3A | Canonical Wnt signaling, golgi lumen, perinuclear endoplasmic reticulum lumen |
| CHD8 | CRISPR/Cas9 heterozygous KO | hiPSC-derived neurons | 1.3E-07 | 1.95 | 91 | NKD2, COL5A2, COL18A1, NCAN, COL14A1, INHBE | 5.7E-07 | 3.48 | 29 | BCAN, FRZB, FREM1, RSPO3, ID1-3, WNT7B | Non-canonical Wnt signaling pathway, ECM, Glypican pathway | |
| Chen et. 2014 | TCF4 | shRNA KD | hiPSC-derived NPCs | 6.2E-01 | 0.93 | 5 | ABCB4, FBXL15, SHF, NELL2, ADAMTSL1 | 6.8E-01 | 0.89 | 1 | PLEKHA5 | NA |
| EHMT1 | shRNA KD | hiPSC-derived NPCs | 1.8E-03 | 2.05 | 23 | NKD2, CAMK2A, COL18A1, VCAN, NCAN, HOXB6 | 1.8E-04 | 4.52 | 10 | BCAN, ID2, ID1, WNT7B, ST6GALNAC3, CORO2B | Golgi lumen, ECM, neuron differentiation | |
| Gigek et al. 2015 | MBD5 | shRNA KD | Human neural stem cells | 8.8E-01 | 0.67 | 6 | NCAN, SMAD9, E2F7, MARCKSL1, IFITM3, TOP1MT | 5.6E-01 | 1.07 | 2 | ID1, KCNJ10 | Perineuronal net, ALK1 signaling |
| SATB2 | shRNA KD | Human neural stem cells | 1.7E-01 | 1.41 | 11 | NCAN, HMGA2, KCND3, SIGMAR1, DDB2, GAD1 | 2.6E-04 | 5.30 | 8 | BCAN, ID1, KCNIP1, KLF10, CORO2B, MPC1 | ECM proteoglycans, GABA synthesis, p53 signaling, Ras mediated sigaling | |
| Zeng et al. 2013 | NRXN1 | shRNA KD | Human neural stem cells | 1.3E-03 | 4.06 | 8 | ZFHX3, NCAN, GFRA1, LRRC8B, DDB2, TMEM151B | 4.2E-02 | 4.68 | 4 | HSPA2, NKD2, COL5A2, KCNIP1 | Wnt signaling, golgi lumen, L-glutamate import, ion channel complex |
| Deneault et al. 2018 | ATRX | CRISPR/Cas9 heterozygous KO | iPSCs | 4.0E-02 | 1.43 | 32 | SHANK3, CAMK2N1, INHBE, IGFBP3, SOCS2, GNB4 | 2.4E-02 | 2.20 | 10 | BCAN, ID2, SHANK3, CAMK2N1, ST6GALNAC3, RHOU | NA |
| CHD8 | CRISPR/Cas9 heterozygous KO | 1.0E+00 | 0.00 | 0 | - | 2.4E-01 | 3.72 | 1 | OLIG3 | NA | ||
| AFF2 | CRISPR/Cas9 heterozygous KO | 8.8E-01 | 0.55 | 2 | CRHBP, GRHL3 | 5.4E-01 | 1.31 | 1 | HSPA2 | NA | ||
| CACNA1C | CRISPR/Cas9 homozygous KO | 1.5E-01 | 1.72 | 6 | INHBE, GRID2, GPC6, SLC7A2, ADM2, CHMP6 | 1.7E-01 | 2.71 | 2 | KLF10, ID2 | NA | ||
| KCNQ2 | CRISPR/Cas9 homozygous KO | 6.3E-01 | 1.01 | 1 | MDGA2 | 1.0E+00 | 0.00 | 0 | - | NA | ||
| SCN2A | CRISPR/Cas9 homozygous KO | 2.0E-04 | 2.06 | 55 | CCND1, NKD2, COL5A2, VCAN, CRTAP, CAMK2A | 1.7E-03 | 2.56 | 16 | FRZB, ID1-3, HSPA2, SMOX, ST6GALNAC3, CORO2B | Voltage gated sodium channel activity, neuronal precursor differentiation | ||
| ASTN2 | CRISPR/Cas9 homozygous KO | 3.3E-01 | 1.33 | 5 | INHBE, FOXI3, STK32B, SEMA6D, MANEAL | 5.5E-01 | 1.25 | 1 | FOXB1 | Glycoproteins, ECM, Axon guidance | ||
| DLGAP2 | CRISPR/Cas9 homozygous KO | 9.3E-01 | 0.38 | 1 | IGFBP3 | 1.0E-01 | 3.76 | 2 | ST6GALNAC3, RHOU | NA | ||
| TENM1 | CRISPR/Cas9 heterozygous KO | 1.8E-01 | 1.40 | 11 | CAMK2N1, SULT1C4, IGFBP3, CELSR1, MOCOS, FBXO25 | 8.2E-01 | 0.59 | 1 | CAMK2N1 | NA | ||
| ANOS1 | CRISPR/Cas9 heterozygous KO | 4.0E-01 | 1.46 | 2 | MDGA2, SHISA3 | 1.0E+00 | 0.00 | 0 | - | NA | ||
| ATRX | CRISPR/Cas9 heterozygous KO | iPSC-derived neurons | 6.7E-07 | 2.36 | 47 | CAMK2A, COL14A1, NCAN, GPC3, SHANK3, TSHZ2 | 2.1E-03 | 2.88 | 12 | WNT3A, FRZB, GPC3, SHANK3, TSHZ2, ARHGAP20 | Cell migration, positive regulation of Wnt, glutamate receptor activity | |
| CHD8 | CRISPR/Cas9 heterozygous KO | 1.0E+00 | 0.00 | 0 | 2.7E-02 | 8.27 | 2 | PCDHGA3, PCDHGA7 | NA | |||
| AFF2 | CRISPR/Cas9 heterozygous KO | 3.9E-01 | 1.49 | 2 | IGFBP3, COL14A1 | 3.4E-02 | 7.27 | 2 | SLITRK2, PIEZO2 | NA | ||
| CACNA1C | CRISPR/Cas9 homozygous KO | 6.6E-01 | 0.94 | 1 | RASGRP1 | 1.0E+00 | 0.00 | 0 | - | NA | ||
| KCNQ2 | CRISPR/Cas9 homozygous KO | 1.0E+00 | 0.00 | 0 | - | 1.3E-04 | 17.19 | 4 | WNT3A, MSX2, PIEZO2, PCDHGA3 | NA | ||
| SCN2A | CRISPR/Cas9 homozygous KO | 1.0E+00 | 0.00 | 0 | - | 4.2E-02 | 6.42 | 2 | PCDHGA3, PCDHGA7 | NA | ||
| ASTN2 | CRISPR/Cas9 homozygous KO | 1.0E+00 | 0.00 | 0 | - | 3.3E-05 | 15.20 | 5 | WNT3A, ID1, MSX2, PIEZO2, PCDHGA3 | NA | ||
| DLGAP2 | CRISPR/Cas9 homozygous KO | 1.0E+00 | 0.00 | 0 | - | 1.0E+00 | 0.00 | 0 | - | NA | ||
| TENM1 | CRISPR/Cas9 heterozygous KO | 2.9E-01 | 1.23 | 12 | GPC3, ARHGAP20, COL14A1, VCAN, SLC10A4, CAMSAP3 | 5.0E-03 | 3.60 | 7 | WNT3A, ID1, MSX2, DPPA4, GPC3, ARHGAP20 | ECM, Glypican pathway, Wnt signaling, signaling patways regulating stem cell pluripotency | ||
| ANOS1 | CRISPR/Cas9 heterozygous KO | 1.0E+00 | 0.00 | 0 | - | 6.6E-03 | 17.77 | 2 | WNT3A, PCDHGA3 | NA | ||
A Fisher’s exact test (FET) and an estimated odds-ratio were used to compute significance of each overlap. When the intersection is greater than six, only six intersecting example genes are displayed for brevity. All overlapping genes found in common with the current study were pooled and subjected to pathway analyses using FET and a genome background set to 17353 genes
KD knockdown, KO knockout