Supplementary Material
Hypoxia-reoxygenation affects whole genome expression in the newborn eye
Embjørg J. Wollen, Przemko Kwinta, Miroslaw Bik-Multanowski, Anna Madetko-
Talowska, Yngve Sejersted, Marianne S.Wright, Clara-Cecilie Günther, Ståle Nygård,
Ola Didrik Saugstad, Jacek J. Pietrzyk
Inventory of Supplemental Digital Content
Section 1 Microarray analysis
Section 2 Table S1 Table S2 Table S3 a-d Table S4 a-c Table S5 Table S6 Table S7 Table S8 Table S9 a-b Table S10 Table S11 Table S12
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Downloaded from iovs.arvojournals.org on 09/28/2021 Section 1.
Microarray analysis
The Affymetrix GeneChip Whole Transcript (WT) sense Target Labeling Assay is
designed to generate amplified and biotinylated sense-strand DNA targets from the
entire expressed genome. The protocol is optimized for the use with the GeneChip
Sense Target (ST) Arrays, where the probes are distributed throughout the entire
length of each transcript.
Initially 100ng of total RNA was mixed with Poly-A RNA controls (GeneChip
Eukaryotic Poly-A Control Kit, Affymetrix). Subsequently cDNA synthesis was
performed with random hexamers tagged with a T7 promoter sequence (GeneChip
WT cDNA Synthesis and Amplification Kit, Sub-kit 1: GeneChip WT cDNA
Synthesis Kit; Affymetrix). The cDNA was then used as a template to produce many
copies of antisense cRNA (GeneChip WT cDNA Synthesis and Amplification Kit,
Sub-kit 2: GeneChip WT cDNA Amplification Kit; Affymetrix).
cRNA was then processed with the cleanup procedure (GeneChip IVT cRNA, cDNA
Cleanup Kit; Affymetrix). cRNA yield was determined by spectrophotometric
measurement (NanoDrop ND-1000; Thermoscientific).
10µg of cRNA was used in the second cycle of cDNA synthesis. Random hexamers
again primed reverse transcription of the cRNA to produce single-stranded DNA in
the sense orientation (GeneChip WT cDNA Synthesis and Amplification Kit, Sub-kit
1: GeneChip WT cDNA Synthesis Kit; Affymetrix). During this step of the
procedure, in order to reproducibly fragment ssDNA, dUTP was incorporated.
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Downloaded from iovs.arvojournals.org on 09/28/2021 Finally, ssDNA was processed with the cleanup procedure (GeneChip IVT cRNA,
cDNA Cleanup Kit; Affymetrix). DNA yield was determined by spectrophotometric
measurement (NanoDrop ND-1000; Thermoscientific).
5, 5 µg of ssDNA was treated with a combination of two enzymes: uracil DNA
glycosylase (UDG) and apurinic/apyrimidinic endonuclease 1 (APE 1), specifically
recognizing the dUTP nucleotides and breaking the DNA strand (GeneChip WT
Terminal Labeling Kit; Affymetrix). Fragmented DNA was labeled by terminal
deoxynucleotidyl transferase (TdT) with the DNA Labeling Reagent, which was
covalently linked to biotin (GeneChip WT Terminal Labeling Kit; Affymetrix).
Fragmented and labeled DNA was further hybridized with the GeneChip Mouse
Gene 1.0 ST Array (Affymetrix). Apart from DNA, the hybridization cocktail
included: Eukaryotic Hybridization Controls (bioB, bioC, bioD, cre), Control
Oligonucleotide B2 (GeneChip Hybridization Control Kit; Affymetrix), 2x
Hybridization Mix, DMSO, water (GeneChip Hybridization, Wash and Stain Kit-
Hybridization Module; Affymetrix). Hybridization was performed at 45°C/ 60 rpm/
17hours ±1hour in a hybridization oven (GeneChip Hybridization Oven 640;
Affymetrix).
After hybridization, arrays were registered in GeneChip Operating Software (GCOS),
washed and stained with the use of GeneChip Fluidics Station 450 (Affymetrix) and
FS450_0007 protocol (GeneChip Hybridization, Wash and Stain Kit-Stain Module;
Wash Buffer A; Wash Buffer B; Affymetrix). Arrays were then scanned with the
GeneChip Scanner 3000 7G (Affymetrix) controlled by GeneChip Operating
Software.
For further statistical analysis **.cel files generated by GeneChip Operating Software
were used.
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Section2.
Table S1 – Primersa used for real-time PCR for mouse transcripts Casp1, Ccl12, Il18, Mt2,
Osmr, and Stat3
Name 5`-3` Primer location GenBank Accession
Casp1 F CAGCTCTGGAGATGGTGAAAGA exon intron junction 5-6 NM_009807.2
Casp1R CTCCTGGATACCATGAGACATGAA
Ccl12 F GGACCAGATGCGGTGAGC exon intron junction 1-2 NM_011331.2
Ccl12 R GCTTGTGATTCTCCTGTAGCTCTTC
Il18 F TGCCATGTCAGAAGACTCTTGC NM_008360.1
exon intron junction 2-3, 3-
Il18 R CCAGGTCTCCATTTTCTTCAGGT 4
Mt2 F TGCCTCCGATGGATCCTG exon intron junction 1-2 NM_008630.2
Mt2 R GGAGCACTTCGCACAGCC
Osmr F CAGATGCACGCTCCCACAT exon intron junction 15-16 NM_011019.3
Osmr R TGACTTTTCCAGTAGCAGACAATGAT
Stat3 F CAGGTAGTGCTGCCCCGTA Exon intron junction 19-20 NM_213659.2
Stat3 R CCTTCACCGTTATTTCCAAACTG
PPIA F CAAATGCTGGACCAAACACAA NM_008907.1
PPIA R TGCCATCCAGCCATTCAGT exon intron junction 4-5
aPrimer concentration 400 nM was used in combination with 50 ng cD.
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Table S3 p-values for all comparisons H21.vs.C21 H40.vs.C21 H60.vs.C21 H100. vs.C21 H100.vs.C100 H40.vs.H21 H60.vs.H21 H100.vs.H21 C100.vs.C21 H21 vs C21 1,00 0,06 0,01 0,00 0,00 0,22 0,00 0,00 0,03 H40 vs C21 0,06 1,00 0,00 0,00 0,00 1,00 0,00 0,00 0,00 H60 vs C21 0,01 0,00 1,00 0,29 0,75 0,00 0,11 0,29 0,86 H100 vs C21 0,00 0,00 0,29 1,00 0,56 0,00 0,69 1,00 0,16 H100 vs C100 0,00 0,00 0,75 0,56 1,00 0,00 0,26 0,56 0,51 H40 vs H21 0,22 1,00 0,00 0,00 0,00 1,00 0,00 0,00 0,00 H60 vs H21 0,00 0,00 0,11 0,69 0,26 0,00 1,00 0,69 0,05 H100 vs H21 0,00 0,00 0,29 1,00 0,56 0,00 0,69 1,00 0,16 C100 vs C21 0,03 0,00 0,86 0,16 0,51 0,00 0,05 0,16 1,00
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Downloaded from iovs.arvojournals.org on 09/28/2021 Table S3a - Genes up- or downregulated after hypoxia and reoxygenation with
FiO2 0.21
Gene name Gene symbol Fold change
Statistical comparison H21 vs. C21, upregulated genes
DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, Y-linked Ddx3y 3.29
eukaryotic translation initiation factor 2, subunit 3, structural Eif2s3y 2.88
gene Y-linked
lipocalin 2 Lcn2 1.61
metallothionein 1 Mt1 1.51
ubiquitously transcribed tetratricopeptide repeat gene, Y Uty 2.53
Statistical comparison H21 vs. C21, downregulated genes
None
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Downloaded from iovs.arvojournals.org on 09/28/2021 Table 3b - Genes up- or downregulated after hypoxia and reoxygenation with FiO2
0.40
Gene name Gene symbol Fold change
Statistical comparison H40 vs. C21, upregulated genes
None
Statistical comparison H40 vs. C21, downregulated genes
None
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Downloaded from iovs.arvojournals.org on 09/28/2021 Table S3c - Genes up- or downregulated after hypoxia and reoxygenation with
FiO2 0.60
Gene name Gene symbol Fold change Statistical comparison H60 vs. C21, upregulated genes aldehyde dehydrogenase 18 family, member A1 Aldh18a1 1.23
ATPase, H+ transporting, lysosomal V0 subunit D1 Atp6v0d1 1.39
complement component 5a receptor 1 C5ar1 1.33
carnitine deficiency-associated gene expressed in Cdv3 1.27 ventricle 3 coatomer protein complex subunit alpha Copa 1.23
D4, zinc and double PHD fingers family 2 Dpf2 1.20 RIKEN cDNA E430029J22 gene E030037K03Rik 1.32
histone deacetylase 5 Hdac5 1.22
histone cluster 2, H3c1 Hist2h3c1 1.23
nuclear prelamin A recognition factor Narf 1.40
oxidative-stress responsive 1 Oxsr1 1.23 pleckstrin homology domain containing, family M Plekhm1 1.21 member 1 RAB7, member RAS oncogene family Rab7 1.23
ring finger protein 220 Rnf220 1.22
SLIT and NTRK-like family, member 1 Slitrk1 1.24
sphingomyelin phosphodiesterase 3, neutral Smpd3 1.21
transcription factor 4 Tcf4 1.24
zinc finger with KRAB and SCAN domains 3 Zkscan3 1.21
Statistical comparison H60 vs. C21, downregulated genes RIKEN cDNA 1500015O10 gene 1500015O10Rik 0.74
cDNA sequence BC031181 BC031181 0.72
calnexin Canx 0.75
cytochrome c oxidase, subunit Va Cox5a 0.79
similar to 60S ribosomal protein L13a Rpl13a 0.75
translocase of outer mitochondrial membrane 22 Tomm22 0.72
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ubiquinol-cytochrome c reductase, complex III Uqcrq 0.79 subunit VII
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Table S3d - Genes up- or downregulated after hypoxia and reoxygenation with
FiO2 1.00
Gene name Gene symbol Fold change
Statistical comparison H100 vs. C21, upregulated genes
anaphase promoting complex subunit 1 Anapc1 1.46
anaphase promoting complex subunit 2 Anapc2 1.29
arrestin domain containing 3 Arrdc3 1.23
ATPase, H+ transporting, lysosomal V0 subunit D1 Atp6v0d1 1.26
chemokine (C-C motif) ligand 12; Ccl12 1.52
coatomer protein complex subunit alpha Copa 1.22
C-terminal binding protein 1 Ctbp1 1.52
DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, Y-linked Ddx3y 2.08
Down syndrome critical region gene 3 Dscr3 1.21
deubiquitinating enzyme 2a Dub2a 1.21
eukaryotic translation initiation factor 2, subunit 3, 1.96 Eif2s3y structural gene Y-linked
furry homolog-like (Drosophila) Fryl 1.37
GTPase activating protein (SH3 domain) binding protein 2 G3bp2 1.45
glutamate receptor, ionotropic, NMDA2A Grin2a 1.23
histone deacetylase 5 Hdac5 1.22
hexokinase 2 Hk2 1.25
insulin-like growth factor I receptor Igf1r 1.21
myosin, heavy polypeptide 9, non-muscle Myh9 1.21
phosphofructokinase, liver, B-type Pfkl 1.23
RAB14, member RAS oncogene family Rab14 2.23
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serine peptidase inhibitor, clade A, member 3N Serpina3n 1.54
signal transducer and activator of transcription 3 Stat3 1.30
TBC1 domain family, member 24 Tbc1d24 1.22
transducin (beta)-like 3 Tbl3 1.22
zinc finger with KRAB and SCAN domains 3 Zkscan3 1.20
Statistical comparison H100 vs. C21, downregulated genes
0.79 asparagine-linked glycosylation 14 homolog (yeast) Alg14 0.74 anaphase promoting complex subunit 1 Anapc1 0.79 hemicentin 1 Hmcn1 0.76 signal sequence receptor, gamma Ssr3
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Table S4a - Gene up- or downregulated after hypoxia and reoxygenation with FiO2
0.40 compared to hypoxia and reoxygenation with FiO2 0.21
Gene name Gene symbol Fold change
Statistical comparison H40 vs. H21, upregulated genes
histone deacetylase 5 Hdac5 1.27
Statistical comparison H40 vs. H21, downregulated genes
DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, Y-linked Ddx3y 0.31
eukaryotic translation initiation factor 2, subunit 3, Eif2s3y 0.31
structural gene Y-linked
ubiquitously transcribed tetratricopeptide repeat gene, Y Uty 0.39
chromosome
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Table S4b - Genes up- or downregulated after hypoxia and reoxygenation with
FiO2 0.60 compared to hypoxia and reoxygenation with FiO2 0.21
Gene name Gene symbol Fold change
Statistical comparison H60 vs. H21, upregulated genes
1.26 BC030046 BC030046 1.20 BC059842 BC059842 1.22 RIKEN cDNA 2310016E02 gene 2310016E02Rik 1.21 anaphase promoting complex subunit 1 Anapc1 1.55 calnexin Canx 1.26 collagen, type I, alpha 2 Col1a2 1.23 collagen, type III, alpha 1 Col3a1 1.23 coatomer protein complex subunit alpha Copa 1.35 COX18 cytochrome c oxidase assembly homolog Cox18 1.23 similar to CtBP1 protein; C-terminal binding protein 1 Ctbp1 1.26 cytochrome b-245, beta polypeptide Cybb 1.26 Der1-like domain family, member 1 Derl1 1.25 Down syndrome critical region gene 3 Dscr3 1.26 RIKEN cDNA E430029J22 gene E030037K03Rik 1.29 frizzled homolog 8 Fzd8 GTPase activating protein (SH3 domain) binding 1.58 G3bp2 protein 2 1.22 golgi-specific brefeldin A-resistance factor 1 Gbf1 1.21 guanosine diphosphate (GDP) dissociation inhibitor 1 Gdi1 1.21 mutL homolog 3 (E coli) Mlh3 1.22 nuclear prelamin A recognition factor Narf
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Downloaded from iovs.arvojournals.org on 09/28/2021 1.23 protocadherin 18 Pcdh18 1.34 RAB7, member RAS oncogene family Rab7 1.25 ring finger protein 220 Rnf220 hypothetical protein LOC100047843; RAR-related 1.28 Rorb orphan receptor beta 1.21 solute carrier family 39 (zinc transporter), member 9 Slc39a9 1.20 serine/threonine kinase 36 Stk36 1.37 transducin (beta)-like 3 Tbl3 1.21 ubiquitin-like modifier activating enzyme 1 Uba1 Statistical comparison H60 vs. H21, downpregulated genes
0.77 BCL2/adenovirus E1B interacting protein 3 Bnip3 DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, Y- 0.26 Ddx3y linked eukaryotic translation initiation factor 2, subunit 3, 0.26 Eif2s3y structural gene Y-linked 0.54 lysine (K)-specific demethylase 5A Jarid1 0.72 ribosomal protein L23a Rpl23a 0.76 ribosomal protein S8 Rps8 0.60 transmembrane protein 165 Tmem165 ubiquitously transcribed tetratricopeptide repeat gene, 0.33 Uty Y chromosome
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Table S4c - Genes up- or downregulated after hypoxia and reoxygenation with
FiO2 1.00 compared to hypoxia and reoxygenation with FiO2 0.21
Gene name Gene symbol Fold change
Statistical comparison H100 vs. H21, upregulated genes
1.31 anaphase promoting complex subunit 1 Anapc1 1.25 anaphase promoting complex subunit 2 Anapc2 1.31 ATX1 (antioxidant protein 1) homolog 1 (yeast) Atox1 1.42 ATPase, H+ transporting, lysosomal V0 subunit D1 Atp6v0d1 1.25 ancient ubiquitous protein 1 Aup1 BC059842 BC059842 1.23 1.21 capicua homolog (Drosophila) Cic 1.23 collagen, type I, alpha 1 Col1a1 1.34 collagen, type I, alpha 2 Col1a2 1.22 coatomer protein complex subunit alpha Copa 1.22 damage specific DNA binding protein 1 Ddb1 1.54 Der1-like domain family, member 1; predicted gene 6737 Derl1 1.21 filamin, alpha Flna 1.25 furry homolog-like (Drosophila) Fryl 1.21 alpha glucosidase 2 alpha neutral subunit Ganab 1.20 gamma-glutamyl carboxylase Ggcx 1.23 H19 fetal liver mRNA H19 1.23 histone deacetylase 5 Hdac5 1.24 hemicentin 1 Hmcn1 1.22 HECT, UBA and WWE domain containing 1 Huwe1
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Downloaded from iovs.arvojournals.org on 09/28/2021 1.25 low density lipoprotein receptor-related protein 1 Lrp1 v-maf musculoaponeurotic fibrosarcoma oncogene family, 1.27 Mafg protein G (avian) 1.28 similar to 60S ribosomal protein L13a Rpl13a 1.21 solute carrier family 38, member 2 Slc38a2 1.24 transducin (beta)-like 3 Tbl3 1.28 zinc finger with KRAB and SCAN domains 3 Zkscan3 Statistical comparison H100 vs. H21, downregulated genes
0.79 olfactory receptor 372 Olfr372 Serpina12 0.78 serine peptidase inhibitor, clade A, member 12
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Table S5 - Genes up- or downregulated after hypoxia and reoxygenation with
FiO2 1.00 compared to normoxia followed by FiO2 1.00.
Gene name Gene symbol Fold change
Statistical comparison H100 vs. C100, upregulated genes
1.35 androgen binding protein epsilon Abpe 1.22 anaphase promoting complex subunit 1 Anapc1 chemokine (C-C motif) ligand 12; similar to monocyte 1.86 Ccl12 chemoattractant protein-5 1.59 cytotoxic T lymphocyte-associated protein 2 alpha Ctla2a 1.76 Der1-like domain family, member 1; predicted gene 6737 Derl1 2.38 deubiquitinating enzyme 2a Dub2a 1.45 EGF, latrophilin seven transmembrane domain containing 1 Eltd1 1.31 FK506 binding protein 5 Fkbp5 1.22 histone cluster 1, H1c Hist1h1c 1.22 hexokinase 2 Hk2 1.64 lipocalin 2 Lcn2 1.55 metallothionein 1 Mt1 2.33 metallothionein 2 Mt2 2.27 RAB14, member RAS oncogene family Rab14 1.36 ring finger protein 220 Rnf220 1.26 syndecan 4 Sdc4 similar to Stat3B; signal transducer and activator of 1.28 Stat3 transcription 3 TATA box binding protein (Tbp)-associated factor, RNA 1.23 Taf1b polymerase I, B 1.36 transducin (beta)-like 3 Tbl3 1.21 thioredoxin interacting protein Txnip
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Downloaded from iovs.arvojournals.org on 09/28/2021 tryptophanyl-tRNA synthetase; similar to tryptophanyl- 1.22 Wars tRNA synthetase Statistical comparison H100 vs. C100, downregulated genes
0.76 calicin Ccin complement component factor h; similar to complement 0.78 Cfh component factor H 0.71 furry homolog-like (Drosophila) Fryl 0.79 RAB7, member RAS oncogene family Rab7 solute carrier family 16 (monocarboxylic acid transporters), 0.77 Slc16a4 member 4 0.73 solute carrier organic anion transporter family, member 1a4 Slco1a4 0.79 YTH domain family 1 Ythdf1
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Table S6 – Genes up- or downregulated after normoxia followed by FiO2 1.00
compared to normoxia.
Gene name Gene symbol Fold change
Statistical comparison C100 vs.C21, upregulated genes
1.22 amyloid beta (A4) precursor-like protein 1 Aplp1 1.29 calnexin Canx 1.21 capicua homolog (Drosophila) Cic DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, Y- 2.02 Ddx3y linked Der1-like domain family, member 1; predicted gene 1.40 Derl1 6737 1.22 discs, large homolog 4 (Drosophila) Dlg4 1.24 F-box and leucine-rich repeat protein 16 Fbxl16 1.75 histone deacetylase 5 Hdac5 1.22 microtubule-associated protein tau Mapt 1.38 N-acetyltransferase 15 (GCN5-related, putative) Nat15 1.28 olfactory receptor 963 Olfr963 1.21 receptor-interacting serine-threonine kinase 4 Ripk4 1.24 ring finger protein 220 Rnf220 1.25 sterile alpha motif domain containing 12 Samd12 ubiquitously transcribed tetratricopeptide repeat gene, 2.02 Uty Y chromosome tryptophanyl-tRNA synthetase; similar to tryptophanyl- 1.26 Wars tRNA synthetase Statistical comparison C100 vs.C21, downregulated genes
0.77 RIKEN cDNA 3110003A17 gene 3110003A17Rik 0.76 anaphase promoting complex subunit 1 Anapc1 0.75 calnexin Canx
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Downloaded from iovs.arvojournals.org on 09/28/2021 0.71 eukaryotic translation initiation factor 4A, isoform 3 Eif4a3 peroxisomal delta3, delta2-enoyl-Coenzyme A 0.79 Peci isomerase 0.72 ribosomal protein L23 Rpl23 0.79 ribosomal protein L23a Rpl23a 0.72 ribosomal protein S27-like Rps27l 0.79 suppressor of Ty 4 homolog 1 Supt4h1 0.74 exportin 7 Xpo7
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Table S7 - Voltage Gated Voltage gated calcium channel complex pathway, comparison H21 vs.C21, upregulated LIST GENE SYMBOL DESC LOC S2Na RESb CORE_ENRICHMENTc 1 CACNA1S CACNA1S CACNA1S 19264 -0.11 0.0102 YES 2 CACNB1 CACNB1 CACNB1 19033 -0.0876 -0.212 YES 3 CACNA2D1 CACNA2D1 CACNA2D1 18841 -0.0759 -0.389 YES 4 CACNA1G CACNA1G CACNA1G 17131 -0.0375 -0.462 YES 5 CACNA1F CACNA1F CACNA1F 16746 -0.0337 -0.522 YES 6 CACNG1 CACNG1 CACNG1 16640 -0.0327 -0.589 YES 7 CACNA1C CACNA1C CACNA1C 16419 -0.0306 -0.647 YES 8 CACNA1E CACNA1E CACNA1E 10851 -0.00342 -0.426 NO 9 CACNA1B CACNA1B CACNA1B 10324 -0.00138 -0.406 NO 10 CACNA1D CACNA1D CACNA1D 8286 0.00658 -0.304 NO 11 CACNB2 CACNB2 CACNB2 7942 0.00806 -0.301 NO 12 CACNG2 CACNG2 CACNG2 7855 0.00844 -0.313 NO 13 CACNB3 CACNB3 CACNB3 7814 0.00863 -0.329 NO 14 CACNB4 CACNB4 CACNB4 7164 0.0114 -0.314 NO 15 CACNA1H CACNA1H CACNA1H 6598 0.0139 -0.31 NO aSignal to noise value is used to rank the genes according to their importance in the
actual comparison.
b Running Enrichment Score is calculated by GSEA to find genes contributing to
pathways significance.
cEnrichment score indicates whether the gene is contributing to the significance of the
pathway Yes or No (greyscaled).
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Table S8 – Mitochondrion pathway in comparison H60 vs. C21, downregulated GENE SYMBOL DESC LIST LOC S2Na RESb CORE_ENRICHMENTc 1 TIMM9 TIMM9 TIMM9 19290 -0.128 0.00897 YES 2 SDHB SDHB SDHB 19283 -0.127 -0.00242 YES 3 ASAH2 ASAH2 ASAH2 19243 -0.12 -0.012 YES 4 NDUFA6 NDUFA6 NDUFA6 19203 -0.115 -0.0209 YES 5 MTHFD2 MTHFD2 MTHFD2 19200 -0.114 -0.0313 YES 6 GCSH GCSH GCSH 19196 -0.114 -0.0416 YES 7 PGS1 PGS1 PGS1 19162 -0.11 -0.0503 YES 8 DECR1 DECR1 DECR1 19154 -0.109 -0.0599 YES 9 CKMT2 CKMT2 CKMT2 19082 -0.102 -0.0661 YES 10 TOMM22 TOMM22 TOMM22 19067 -0.101 -0.0747 YES 11 NDUFA1 NDUFA1 NDUFA1 19054 -0.0995 -0.0833 YES 12 ATP5E ATP5E ATP5E 19032 -0.0983 -0.0913 YES 13 PTS PTS PTS 19001 -0.0962 -0.0987 YES 14 COX7A1 COX7A1 COX7A1 19000 -0.0961 -0.107 YES 15 PECI PECI PECI 18959 -0.0931 -0.114 YES 16 ECHS1 ECHS1 ECHS1 18942 -0.0919 -0.122 YES 17 DUT DUT DUT 18894 -0.0892 -0.128 YES 18 PTGES2 PTGES2 PTGES2 18887 -0.0886 -0.136 YES 19 ATP5O ATP5O ATP5O 18860 -0.0871 -0.142 YES 20 TMEM126A TMEM126A TMEM126A 18839 -0.0861 -0.149 YES 21 NDUFA2 NDUFA2 NDUFA2 18799 -0.0843 -0.155 YES 22 MRPL12 MRPL12 MRPL12 18783 -0.0837 -0.162 YES 23 MRPL41 MRPL41 MRPL41 18766 -0.0829 -0.169 YES 24 NDUFS3 NDUFS3 NDUFS3 18719 -0.081 -0.174 YES 25 MRPS36 MRPS36 MRPS36 18716 -0.0809 -0.181 YES 26 MOSC2 MOSC2 MOSC2 18682 -0.0798 -0.187 YES 27 MRPS18C MRPS18C MRPS18C 18668 -0.0792 -0.194 YES 28 NDUFB6 NDUFB6 NDUFB6 18648 -0.0782 -0.2 YES 29 NDUFA11 NDUFA11 NDUFA11 18641 -0.078 -0.207 YES 30 MRPS35 MRPS35 MRPS35 18614 -0.0769 -0.212 YES 31 CASQ1 CASQ1 CASQ1 18612 -0.0769 -0.219 YES 32 HSPD1 HSPD1 HSPD1 18602 -0.0766 -0.226 YES 33 SUCLG1 SUCLG1 SUCLG1 18587 -0.0761 -0.232 YES 34 NDUFA8 NDUFA8 NDUFA8 18576 -0.0756 -0.239 YES 35 TUFM TUFM TUFM 18502 -0.0732 -0.242 YES 36 SUCLA2 SUCLA2 SUCLA2 18476 -0.0722 -0.247 YES 37 COQ7 COQ7 COQ7 18446 -0.0713 -0.252 YES 38 COX18 COX18 COX18 18364 -0.0687 -0.254 YES 39 GATM GATM GATM 18356 -0.0685 -0.26 YES 40 GRPEL1 GRPEL1 GRPEL1 18352 -0.0684 -0.266 YES 41 ATP5F1 ATP5F1 ATP5F1 18273 -0.0665 -0.269 YES
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Downloaded from iovs.arvojournals.org on 09/28/2021 42 TIMM50 TIMM50 TIMM50 18262 -0.0663 -0.274 YES 43 DGUOK DGUOK DGUOK 18209 -0.0648 -0.278 YES 44 MRPS24 MRPS24 MRPS24 18138 -0.063 -0.28 YES 45 ATP5G3 ATP5G3 ATP5G3 18123 -0.0626 -0.285 YES 46 MRPS22 MRPS22 MRPS22 18105 -0.0622 -0.29 YES 47 GPX4 GPX4 GPX4 18097 -0.062 -0.295 YES 48 PDK3 PDK3 PDK3 18068 -0.0616 -0.299 YES 49 ETFA ETFA ETFA 18054 -0.0613 -0.304 YES 50 DNAJA3 DNAJA3 DNAJA3 18011 -0.0605 -0.308 YES 51 PHB2 PHB2 PHB2 17991 -0.06 -0.312 YES 52 HSPE1 HSPE1 HSPE1 17896 -0.0583 -0.313 YES 53 BCKDHA BCKDHA BCKDHA 17881 -0.0581 -0.317 YES 54 MYLC2PL MYLC2PL MYLC2PL 17862 -0.0578 -0.322 YES 55 SURF1 SURF1 SURF1 17857 -0.0577 -0.327 YES 56 GLRX5 GLRX5 GLRX5 17801 -0.0568 -0.329 YES 57 SLC25A1 SLC25A1 SLC25A1 17795 -0.0568 -0.334 YES 58 DHRS4 DHRS4 DHRS4 17780 -0.0565 -0.338 YES 59 TFAM TFAM TFAM 17753 -0.0562 -0.342 YES 60 NDUFV1 NDUFV1 NDUFV1 17734 -0.0558 -0.346 YES 61 NDUFS5 NDUFS5 NDUFS5 17731 -0.0557 -0.351 YES 62 NDUFA4 NDUFA4 NDUFA4 17718 -0.0554 -0.356 YES 63 MTX2 MTX2 MTX2 17628 -0.0537 -0.356 YES 64 MRPS11 MRPS11 MRPS11 17619 -0.0536 -0.361 YES 65 BCKDHB BCKDHB BCKDHB 17577 -0.053 -0.364 YES 66 CYC1 CYC1 CYC1 17573 -0.0529 -0.368 YES 67 HINT2 HINT2 HINT2 17569 -0.0528 -0.373 YES 68 ACADS ACADS ACADS 17456 -0.0512 -0.372 YES 69 MRPS28 MRPS28 MRPS28 17453 -0.0511 -0.376 YES 70 NDUFA9 NDUFA9 NDUFA9 17447 -0.0511 -0.381 YES 71 MRPL51 MRPL51 MRPL51 17430 -0.0508 -0.385 YES 72 COQ6 COQ6 COQ6 17420 -0.0506 -0.389 YES 73 SLC25A3 SLC25A3 SLC25A3 17414 -0.0505 -0.393 YES 74 ECSIT ECSIT ECSIT 17393 -0.0501 -0.397 YES 75 ATP5G1 ATP5G1 ATP5G1 17380 -0.05 -0.401 YES 76 FIBP FIBP FIBP 17372 -0.0499 -0.405 YES 77 TRIAP1 TRIAP1 TRIAP1 17367 -0.0498 -0.409 YES 78 ETFB ETFB ETFB 17351 -0.0496 -0.413 YES 79 ACADVL ACADVL ACADVL 17347 -0.0495 -0.417 YES 80 MRPL10 MRPL10 MRPL10 17335 -0.0493 -0.421 YES 81 MRPL23 MRPL23 MRPL23 17332 -0.0493 -0.426 YES 82 MRPS12 MRPS12 MRPS12 17294 -0.0486 -0.428 YES 83 ABCB6 ABCB6 ABCB6 17200 -0.0472 -0.428 YES 84 FIS1 FIS1 FIS1 17159 -0.0465 -0.43 YES 85 MECR MECR MECR 17150 -0.0464 -0.434 YES 86 MTCH1 MTCH1 MTCH1 17047 -0.0451 -0.433 YES 87 MCAT MCAT MCAT 16973 -0.0441 -0.433 YES
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Downloaded from iovs.arvojournals.org on 09/28/2021 88 ARG2 ARG2 ARG2 16896 -0.0432 -0.433 YES 89 SOD1 SOD1 SOD1 16893 -0.0432 -0.437 YES 90 ATP5J ATP5J ATP5J 16809 -0.0421 -0.437 YES 91 MRPS31 MRPS31 MRPS31 16752 -0.0415 -0.438 YES 92 NDUFA13 NDUFA13 NDUFA13 16581 -0.0397 -0.433 YES 93 ATP5D ATP5D ATP5D 16558 -0.0394 -0.435 YES 94 MTRF1 MTRF1 MTRF1 16546 -0.0394 -0.438 YES 95 CLPX CLPX CLPX 16501 -0.039 -0.439 YES 96 RAF1 RAF1 RAF1 16499 -0.039 -0.443 YES 97 MIPEP MIPEP MIPEP 16485 -0.0388 -0.446 YES 98 MRPL55 MRPL55 MRPL55 16353 -0.0374 -0.442 YES 99 DNAJC19 DNAJC19 DNAJC19 16348 -0.0373 -0.446 YES 100 MRPS18A MRPS18A MRPS18A 16257 -0.0363 -0.444 YES 101 CHCHD3 CHCHD3 CHCHD3 16250 -0.0362 -0.447 YES 102 IDH2 IDH2 IDH2 16221 -0.036 -0.449 YES 103 ATPIF1 ATPIF1 ATPIF1 16163 -0.0355 -0.45 YES 104 COX6B2 COX6B2 COX6B2 16134 -0.0353 -0.451 YES 105 OAT OAT OAT 16130 -0.0353 -0.454 YES 106 ME3 ME3 ME3 16081 -0.0349 -0.455 YES 107 AGPAT5 AGPAT5 AGPAT5 16065 -0.0347 -0.458 YES 108 SDHD SDHD SDHD 16022 -0.0343 -0.459 YES 109 SLC25A11 SLC25A11 SLC25A11 15912 -0.0334 -0.456 YES 110 THG1L THG1L THG1L 15795 -0.0323 -0.453 YES 111 MSRB2 MSRB2 MSRB2 15705 -0.0316 -0.451 YES 112 HTRA2 HTRA2 HTRA2 15703 -0.0316 -0.454 YES 113 FPGS FPGS FPGS 15671 -0.0314 -0.455 YES 114 GSTZ1 GSTZ1 GSTZ1 15661 -0.0313 -0.458 YES 115 MSTO1 MSTO1 MSTO1 15622 -0.031 -0.459 YES 116 TIMM10 TIMM10 TIMM10 15613 -0.0309 -0.461 YES 117 TRMU TRMU TRMU 15541 -0.0302 -0.46 YES 118 BAX BAX BAX 15469 -0.0295 -0.459 YES 119 VDAC2 VDAC2 VDAC2 15462 -0.0295 -0.462 YES 120 PRDX5 PRDX5 PRDX5 15356 -0.0285 -0.459 YES 121 TIMM8B TIMM8B TIMM8B 15353 -0.0285 -0.461 YES 122 LRPPRC LRPPRC LRPPRC 15285 -0.0279 -0.46 YES 123 PTRF PTRF PTRF 15282 -0.0279 -0.463 YES 124 NT5M NT5M NT5M 15206 -0.0273 -0.462 YES 125 TSFM TSFM TSFM 15132 -0.0269 -0.46 YES 126 ACOT9 ACOT9 ACOT9 15079 -0.0265 -0.46 YES 127 MRPS21 MRPS21 MRPS21 15069 -0.0264 -0.462 YES 128 UQCRH UQCRH UQCRH 15024 -0.026 -0.462 YES 129 CPT1B CPT1B CPT1B 15007 -0.0259 -0.464 YES 130 UQCRB UQCRB UQCRB 14981 -0.0257 -0.465 YES 131 COX4NB COX4NB COX4NB 14924 -0.0253 -0.464 YES 132 UQCRC1 UQCRC1 UQCRC1 14918 -0.0252 -0.466 YES 133 SCO1 SCO1 SCO1 14712 -0.0237 -0.458 NO
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Downloaded from iovs.arvojournals.org on 09/28/2021 134 NDUFS7 NDUFS7 NDUFS7 14674 -0.0234 -0.458 NO 135 MRPL40 MRPL40 MRPL40 14597 -0.0228 -0.456 NO 136 BPHL BPHL BPHL 14562 -0.0225 -0.456 NO 137 HAX1 HAX1 HAX1 14540 -0.0223 -0.457 NO 138 HADH HADH HADH 14480 -0.0219 -0.456 NO 139 MRPS15 MRPS15 MRPS15 14478 -0.0219 -0.458 NO 140 IMMT IMMT IMMT 14471 -0.0218 -0.46 NO 141 SMCP SMCP SMCP 14403 -0.0214 -0.458 NO 142 NDUFS8 NDUFS8 NDUFS8 14387 -0.0212 -0.46 NO 143 TIMM44 TIMM44 TIMM44 14357 -0.021 -0.46 NO 144 VDAC1 VDAC1 VDAC1 14322 -0.0208 -0.46 NO 145 GBAS GBAS GBAS 14242 -0.0202 -0.458 NO 146 SDHA SDHA SDHA 14192 -0.0198 -0.457 NO 147 SPG7 SPG7 SPG7 14189 -0.0198 -0.459 NO 148 GLYAT GLYAT GLYAT 14170 -0.0197 -0.46 NO 149 ATP5A1 ATP5A1 ATP5A1 14064 -0.0189 -0.456 NO 150 ACP6 ACP6 ACP6 14024 -0.0186 -0.456 NO 151 ALDH4A1 ALDH4A1 ALDH4A1 13899 -0.0177 -0.451 NO 152 MRPS10 MRPS10 MRPS10 13885 -0.0176 -0.452 NO 153 ALDH5A1 ALDH5A1 ALDH5A1 13871 -0.0176 -0.453 NO 154 MTIF3 MTIF3 MTIF3 13822 -0.0172 -0.452 NO 155 DIABLO DIABLO DIABLO 13783 -0.0169 -0.452 NO 156 ATP5C1 ATP5C1 ATP5C1 13711 -0.0165 -0.449 NO 157 FDX1 FDX1 FDX1 13687 -0.0163 -0.45 NO 158 LETM1 LETM1 LETM1 13685 -0.0163 -0.451 NO 159 BCKDK BCKDK BCKDK 13618 -0.0158 -0.449 NO 160 HSD3B1 HSD3B1 HSD3B1 13603 -0.0157 -0.45 NO 161 RAB11FIP5 RAB11FIP5 RAB11FIP5 13580 -0.0156 -0.45 NO 162 TIMM17B TIMM17B TIMM17B 13534 -0.0153 -0.449 NO 163 CASP7 CASP7 CASP7 13466 -0.0147 -0.447 NO 164 TRNT1 TRNT1 TRNT1 13433 -0.0145 -0.447 NO 165 AMACR AMACR AMACR 13368 -0.014 -0.445 NO 166 HMGCS2 HMGCS2 HMGCS2 13333 -0.0138 -0.444 NO 167 MTHFD1 MTHFD1 MTHFD1 13313 -0.0137 -0.445 NO 168 TFB2M TFB2M TFB2M 13254 -0.0133 -0.443 NO 169 ACADM ACADM ACADM 13241 -0.0133 -0.444 NO 170 ACAT1 ACAT1 ACAT1 13073 -0.0122 -0.436 NO 171 NME4 NME4 NME4 13051 -0.0121 -0.436 NO 172 SLC25A4 SLC25A4 SLC25A4 13010 -0.0118 -0.435 NO 173 PINK1 PINK1 PINK1 12937 -0.0115 -0.432 NO 174 AMT AMT AMT 12871 -0.0111 -0.43 NO 175 ATP5B ATP5B ATP5B 12813 -0.0108 -0.428 NO 176 CPS1 CPS1 CPS1 12811 -0.0108 -0.429 NO 177 SARS2 SARS2 SARS2 12770 -0.0106 -0.428 NO 178 SLC25A14 SLC25A14 SLC25A14 12763 -0.0105 -0.429 NO 179 SOD2 SOD2 SOD2 12673 -0.00999 -0.425 NO
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Downloaded from iovs.arvojournals.org on 09/28/2021 180 AFG3L2 AFG3L2 AFG3L2 12662 -0.00995 -0.425 NO 181 SDHC SDHC SDHC 12330 -0.00786 -0.409 NO 182 BNIP3 BNIP3 BNIP3 12264 -0.00742 -0.406 NO 183 SLC25A15 SLC25A15 SLC25A15 12216 -0.00715 -0.404 NO 184 CS CS CS 12213 -0.00715 -0.405 NO 185 BCL2L1 BCL2L1 BCL2L1 12102 -0.00659 -0.4 NO 186 TMEM143 TMEM143 TMEM143 11598 -0.0039 -0.374 NO 187 NDUFS2 NDUFS2 NDUFS2 11461 -0.00329 -0.368 NO 188 FDXR FDXR FDXR 11422 -0.00305 -0.366 NO 189 BBC3 BBC3 BBC3 11239 -0.00208 -0.357 NO 190 MTIF2 MTIF2 MTIF2 11222 -0.00199 -0.356 NO 191 PMAIP1 PMAIP1 PMAIP1 11167 -0.00169 -0.353 NO 192 TIMM17A TIMM17A TIMM17A 11102 -0.00134 -0.35 NO 193 MCL1 MCL1 MCL1 10927 -0.00037 -0.341 NO - 194 TOMM34 TOMM34 TOMM34 10883 0.000116 -0.339 NO -9.38e- 195 OXCT1 OXCT1 OXCT1 10880 05 -0.339 NO 196 UCP3 UCP3 UCP3 10861 2.37e-05 -0.338 NO 197 AK3 AK3 AK3 10860 2.52e-05 -0.338 NO 198 AASS AASS AASS 10793 0.000355 -0.335 NO 199 TRAK1 TRAK1 TRAK1 10520 0.00173 -0.32 NO 200 SLC9A6 SLC9A6 SLC9A6 10506 0.00178 -0.32 NO 201 PCCB PCCB PCCB 10470 0.00194 -0.318 NO 202 GHITM GHITM GHITM 10447 0.00206 -0.317 NO 203 MRPL32 MRPL32 MRPL32 10389 0.00233 -0.314 NO 204 PDHA1 PDHA1 PDHA1 10171 0.00353 -0.303 NO 205 COQ4 COQ4 COQ4 10063 0.00401 -0.298 NO 206 PET112L PET112L PET112L 9994 0.00436 -0.295 NO 207 NDUFS1 NDUFS1 NDUFS1 9986 0.00441 -0.295 NO 208 CPOX CPOX CPOX 9897 0.00486 -0.291 NO 209 PHB PHB PHB 9845 0.00512 -0.289 NO 210 POLG2 POLG2 POLG2 9798 0.0054 -0.287 NO 211 SLC22A4 SLC22A4 SLC22A4 9792 0.00542 -0.287 NO 212 GCDH GCDH GCDH 9790 0.00542 -0.287 NO 213 MRPL52 MRPL52 MRPL52 9755 0.00557 -0.286 NO 214 DLD DLD DLD 9741 0.00569 -0.286 NO 215 DMGDH DMGDH DMGDH 9735 0.00572 -0.286 NO 216 MPV17 MPV17 MPV17 9729 0.00574 -0.286 NO 217 NR3C1 NR3C1 NR3C1 9457 0.00724 -0.273 NO 218 LDHD LDHD LDHD 9446 0.00733 -0.273 NO 219 HCCS HCCS HCCS 9382 0.00764 -0.27 NO 220 COX8C COX8C COX8C 9379 0.00765 -0.271 NO 221 SUPV3L1 SUPV3L1 SUPV3L1 9231 0.00845 -0.264 NO 222 COX11 COX11 COX11 9220 0.0085 -0.264 NO 223 CRY1 CRY1 CRY1 8892 0.0101 -0.248 NO
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Downloaded from iovs.arvojournals.org on 09/28/2021 224 ABCE1 ABCE1 ABCE1 8680 0.0112 -0.238 NO 225 IDH3B IDH3B IDH3B 8621 0.0116 -0.236 NO 226 FXN FXN FXN 8573 0.0118 -0.234 NO 227 OPA1 OPA1 OPA1 8570 0.0118 -0.235 NO 228 TXNRD2 TXNRD2 TXNRD2 8519 0.0121 -0.234 NO 229 PMPCA PMPCA PMPCA 8506 0.0122 -0.234 NO 230 PDK1 PDK1 PDK1 8334 0.013 -0.227 NO 231 RHOT2 RHOT2 RHOT2 8170 0.0139 -0.219 NO 232 POLRMT POLRMT POLRMT 8127 0.0141 -0.218 NO 233 BCS1L BCS1L BCS1L 8069 0.0144 -0.217 NO 234 ABCB7 ABCB7 ABCB7 8066 0.0144 -0.218 NO 235 FOXRED1 FOXRED1 FOXRED1 7980 0.0148 -0.215 NO 236 BAK1 BAK1 BAK1 7870 0.0153 -0.21 NO 237 GLRX2 GLRX2 GLRX2 7850 0.0154 -0.211 NO 238 ACO2 ACO2 ACO2 7722 0.0162 -0.206 NO 239 NFS1 NFS1 NFS1 7560 0.017 -0.199 NO 240 GLUD1 GLUD1 GLUD1 7526 0.0172 -0.198 NO 241 BZRAP1 BZRAP1 BZRAP1 7251 0.0185 -0.186 NO 242 ABCF2 ABCF2 ABCF2 7204 0.0187 -0.185 NO 243 NNT NNT NNT 7155 0.0189 -0.184 NO 244 NDUFS4 NDUFS4 NDUFS4 7088 0.0193 -0.183 NO 245 POLG POLG POLG 6992 0.0198 -0.179 NO 246 RHOT1 RHOT1 RHOT1 6959 0.02 -0.179 NO 247 SARDH SARDH SARDH 6901 0.0203 -0.178 NO 248 BID BID BID 6720 0.0214 -0.171 NO 249 L2HGDH L2HGDH L2HGDH 6524 0.0223 -0.163 NO 250 BDH2 BDH2 BDH2 6285 0.0236 -0.152 NO 251 NAPG NAPG NAPG 6156 0.0243 -0.148 NO 252 BCL2 BCL2 BCL2 6153 0.0243 -0.15 NO 253 KARS KARS KARS 6065 0.0249 -0.147 NO 254 ABCB8 ABCB8 ABCB8 6022 0.0251 -0.148 NO 255 MUT MUT MUT 5799 0.0263 -0.138 NO 256 OXA1L OXA1L OXA1L 5785 0.0263 -0.14 NO 257 HSD3B2 HSD3B2 HSD3B2 5569 0.0275 -0.131 NO 258 MSRB3 MSRB3 MSRB3 5562 0.0275 -0.133 NO 259 CCDC39 CCDC39 CCDC39 5413 0.0285 -0.128 NO 260 SLC25A12 SLC25A12 SLC25A12 5174 0.03 -0.118 NO 261 TBRG4 TBRG4 TBRG4 5057 0.0306 -0.115 NO 262 SLC25A13 SLC25A13 SLC25A13 4774 0.0324 -0.103 NO 263 ACADSB ACADSB ACADSB 4746 0.0326 -0.105 NO 264 CASP8 CASP8 CASP8 4699 0.0329 -0.105 NO 265 DBT DBT DBT 4597 0.0335 -0.103 NO 266 ACN9 ACN9 ACN9 4337 0.0352 -0.0925 NO 267 NIPSNAP1 NIPSNAP1 NIPSNAP1 4108 0.0368 -0.0839 NO 268 PPOX PPOX PPOX 3946 0.0379 -0.0788 NO 269 PITRM1 PITRM1 PITRM1 3554 0.0408 -0.0619 NO
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Downloaded from iovs.arvojournals.org on 09/28/2021 270 ESR2 ESR2 ESR2 3433 0.0419 -0.0594 NO 271 BCL2L10 BCL2L10 BCL2L10 3366 0.0424 -0.0597 NO 272 CPT1A CPT1A CPT1A 3009 0.0454 -0.045 NO 273 BCAT2 BCAT2 BCAT2 2926 0.0461 -0.0449 NO 274 GLS2 GLS2 GLS2 2785 0.0474 -0.0418 NO 275 PSEN1 PSEN1 PSEN1 2413 0.0511 -0.0268 NO 276 ACOT2 ACOT2 ACOT2 2275 0.0527 -0.0243 NO 277 SLC25A22 SLC25A22 SLC25A22 2232 0.0532 -0.0269 NO 278 OGDH OGDH OGDH 2189 0.0537 -0.0296 NO 279 PCK2 PCK2 PCK2 2135 0.0541 -0.0317 NO 280 CLN3 CLN3 CLN3 1809 0.0581 -0.0197 NO 281 PDK4 PDK4 PDK4 1788 0.0584 -0.024 NO 282 COX15 COX15 COX15 1641 0.0606 -0.0217 NO 283 ALAS2 ALAS2 ALAS2 1582 0.0615 -0.0242 NO 284 SLC25A27 SLC25A27 SLC25A27 1492 0.063 -0.0252 NO 285 MFN2 MFN2 MFN2 1337 0.0655 -0.0229 NO 286 OXSM OXSM OXSM 1233 0.0676 -0.0235 NO 287 SHMT2 SHMT2 SHMT2 1152 0.0696 -0.0255 NO 288 SMCR7L SMCR7L SMCR7L 1122 0.0702 -0.0304 NO 289 ABAT ABAT ABAT 1048 0.0718 -0.033 NO 290 MAOB MAOB MAOB 898 0.0759 -0.0318 NO 291 D2HGDH D2HGDH D2HGDH 576 0.0881 -0.0219 NO
aSignal to noise value is used to rank the genes according to their import ance in the
actual comparison.
b Running Enrichment Score is calculated by GSEA to find genes contributing to
pathways significance.
cEnrichment score indicates whether the gene is contributing to the significance of the
pathway Yes or No (greyscaled).
28
Downloaded from iovs.arvojournals.org on 09/28/2021
Table S9a – Regulation of Ras Protein Signaling in comparison H60 vs. C21, upregulated GENE SYMBOL DESC LIST LOC S2Na RESb CORE_ENRICHMENTc 1 ABRA ABRA ABRA 252 0.112 0.155 YES 2 MFN2 MFN2 MFN2 1337 0.0655 0.198 YES 3 FGD4 FGD4 FGD4 1997 0.0556 0.248 YES 4 FGD5 FGD5 FGD5 2231 0.0532 0.316 YES 5 RALBP1 RALBP1 RALBP1 2794 0.0474 0.358 YES 6 FGD3 FGD3 FGD3 2955 0.0459 0.419 YES 7 ARHGAP27 ARHGAP27 ARHGAP27 3011 0.0454 0.484 YES 8 FGD6 FGD6 FGD6 3250 0.0433 0.537 YES 9 TSC1 TSC1 TSC1 4443 0.0345 0.527 YES 10 NOTCH2 NOTCH2 NOTCH2 4645 0.0332 0.567 YES 11 ALS2 ALS2 ALS2 4823 0.0321 0.606 YES 12 RASGRP4 RASGRP4 RASGRP4 5375 0.0288 0.621 YES 13 PLCE1 PLCE1 PLCE1 6288 0.0236 0.609 YES 14 NF1 NF1 NF1 6487 0.0226 0.633 YES 15 FGD2 FGD2 FGD2 9060 0.0093 0.515 NO 16 FGD1 FGD1 FGD1 9470 0.00718 0.505 NO 17 ARF6 ARF6 ARF6 9883 0.00492 0.491 NO 18 RAC1 RAC1 RAC1 10619 0.00122 0.455 NO Table S9b - Regulation of Ras Protein Signaling in comparison H100 vs. C21, upregulated GENE SYMBOL DESC LIST LOC S2Na RESb CORE_ENRICHMENTc 1 ABRA ABRA ABRA 1191 0.0779 0.0701 YES 2 MFN2 MFN2 MFN2 1602 0.0659 0.16 YES 3 RALBP1 RALBP1 RALBP1 1910 0.0601 0.245 YES 4 ALS2 ALS2 ALS2 2806 0.0476 0.279 YES 5 FGD6 FGD6 FGD6 2826 0.0473 0.358 YES 6 ARHGAP27 ARHGAP27 ARHGAP27 3016 0.045 0.424 YES 7 TSC1 TSC1 TSC1 4003 0.0361 0.434 YES 8 ARF6 ARF6 ARF6 4365 0.0334 0.472 YES 9 FGD3 FGD3 FGD3 4373 0.0334 0.528 YES 10 FGD5 FGD5 FGD5 4580 0.0322 0.571 YES 11 RASGRP4 RASGRP4 RASGRP4 5663 0.0251 0.558 NO 12 FGD4 FGD4 FGD4 8030 0.012 0.456 NO 13 NOTCH2 NOTCH2 NOTCH2 8313 0.0107 0.46 NO 14 NF1 NF1 NF1 9537 0.00462 0.405 NO 15 RAC1 RAC1 RAC1 12617 -0.0105 0.264 NO 16 PLCE1 PLCE1 PLCE1 12795 -0.0113 0.274 NO 17 FGD1 FGD1 FGD1 13619 -0.0162 0.259 NO 18 FGD2 FGD2 FGD2 14948 -0.0247 0.232 NO
29
Downloaded from iovs.arvojournals.org on 09/28/2021 aSignal to noise value is used to rank the genes according to their importance in the
actual comparison.
b Running Enrichment Score is calculated by GSEA to find genes contributing to
pathways significance.
cEnrichment score indicates whether the gene is contributing to the significance of the
pathway Yes or No (greyscaled).
30
Downloaded from iovs.arvojournals.org on 09/28/2021 Table S10 – Apoptosis pathway in comparison H21 vs. C21, upregulated GENE SYMBOL DESC LIST LOC S2Na RESb CORE_ENRICHMENTc 1 IL1R1 IL1R1 IL1R1 228 0.141 0.0671 YES 2 IL3 IL3 IL3 326 0.124 0.131 YES 3 IL1B IL1B IL1B 1587 0.0596 0.0998 YES 4 CASP8 CASP8 CASP8 1633 0.0587 0.13 YES 5 CASP6 CASP6 CASP6 1895 0.054 0.147 YES 6 PIK3R5 PIK3R5 PIK3R5 2219 0.0476 0.157 YES 7 RIPK1 RIPK1 RIPK1 2386 0.0452 0.173 YES 8 DFFB DFFB DFFB 2420 0.0448 0.197 YES 9 IL1A IL1A IL1A 2658 0.0417 0.208 YES 10 BAD BAD BAD 2761 0.0402 0.225 YES 11 CASP9 CASP9 CASP9 2872 0.0388 0.241 YES 12 MYD88 MYD88 MYD88 3148 0.0361 0.247 YES 13 PIK3CA PIK3CA PIK3CA 3362 0.0343 0.255 YES 14 CASP3 CASP3 CASP3 3386 0.0342 0.273 YES 15 IKBKG IKBKG IKBKG 3668 0.0316 0.276 YES 16 BID BID BID 3701 0.0313 0.292 YES 17 IRAK3 IRAK3 IRAK3 3781 0.0307 0.305 YES 18 BAX BAX BAX 4503 0.0254 0.282 YES 19 ENDOG ENDOG ENDOG 4577 0.025 0.292 YES 20 IKBKB IKBKB IKBKB 4716 0.0243 0.299 YES 21 IRAK1 IRAK1 IRAK1 4725 0.0242 0.312 YES 22 PPP3CA PPP3CA PPP3CA 4917 0.0229 0.315 YES 23 NFKB1 NFKB1 NFKB1 5185 0.0214 0.313 YES 24 CASP7 CASP7 CASP7 5209 0.0213 0.324 YES 25 IRAK2 IRAK2 IRAK2 5264 0.0209 0.332 YES 26 CHUK CHUK CHUK 5280 0.0208 0.343 YES 27 PIK3CB PIK3CB PIK3CB 5329 0.0205 0.352 YES 28 PRKAR2A PRKAR2A PRKAR2A 5518 0.0194 0.353 YES 29 NFKBIA NFKBIA NFKBIA 5767 0.0183 0.351 NO 30 PRKACB PRKACB PRKACB 6035 0.0169 0.347 NO 31 TNFRSF1A TNFRSF1A TNFRSF1A 6184 0.0161 0.348 NO 32 MAP3K14 MAP3K14 MAP3K14 6400 0.0149 0.345 NO 33 RELA RELA RELA 6603 0.0139 0.342 NO 34 CAPN1 CAPN1 CAPN1 6662 0.0137 0.347 NO 35 APAF1 APAF1 APAF1 6793 0.013 0.348 NO 36 PIK3CD PIK3CD PIK3CD 6931 0.0124 0.348 NO 37 DFFA DFFA DFFA 7284 0.011 0.336 NO 38 IRAK4 IRAK4 IRAK4 7463 0.0102 0.332 NO 39 PRKAR2B PRKAR2B PRKAR2B 7750 0.00888 0.322 NO 40 TRADD TRADD TRADD 7967 0.00795 0.316 NO 41 BCL2 BCL2 BCL2 8005 0.00779 0.318 NO 42 PRKAR1B PRKAR1B PRKAR1B 8409 0.00613 0.301 NO 43 CAPN2 CAPN2 CAPN2 8510 0.00569 0.299 NO 44 AKT3 AKT3 AKT3 8806 0.0045 0.286 NO
31
Downloaded from iovs.arvojournals.org on 09/28/2021 45 PPP3CC PPP3CC PPP3CC 8847 0.00438 0.286 NO 46 BIRC2 BIRC2 BIRC2 8971 0.00394 0.282 NO 47 FAS FAS FAS 9417 0.00211 0.26 NO 48 PPP3R1 PPP3R1 PPP3R1 9538 0.00167 0.255 NO 49 PPP3R2 PPP3R2 PPP3R2 9961 4.14e-05 0.233 NO 50 NTRK1 NTRK1 NTRK1 10756 -0.00306 0.194 NO 51 BIRC3 BIRC3 BIRC3 11075 -0.00426 0.18 NO 52 PPP3CB PPP3CB PPP3CB 11191 -0.00467 0.177 NO 53 ATM ATM ATM 11224 -0.00481 0.178 NO 54 CFLAR CFLAR CFLAR 11361 -0.00536 0.174 NO 55 TNF TNF TNF 11411 -0.00554 0.174 NO 56 PIK3R1 PIK3R1 PIK3R1 11789 -0.00695 0.159 NO 57 TRAF2 TRAF2 TRAF2 11942 -0.00753 0.155 NO 58 PRKAR1A PRKAR1A PRKAR1A 12543 -0.00995 0.13 NO 59 TNFRSF10B TNFRSF10B TNFRSF10B 12775 -0.011 0.124 NO 60 IL3RA IL3RA IL3RA 13689 -0.015 0.0853 NO 61 AKT1 AKT1 AKT1 14073 -0.0168 0.075 NO 62 NFKB2 NFKB2 NFKB2 14644 -0.0197 0.0565 NO 63 AKT2 AKT2 AKT2 14871 -0.0208 0.0565 NO 64 PIK3R3 PIK3R3 PIK3R3 15348 -0.0234 0.0449 NO 65 PIK3R2 PIK3R2 PIK3R2 15370 -0.0235 0.057 NO 66 TNFSF10 TNFSF10 TNFSF10 16295 -0.0297 0.0259 NO 67 PIK3CG PIK3CG PIK3CG 16348 -0.0301 0.04 NO 68 IL1RAP IL1RAP IL1RAP 16412 -0.0305 0.0538 NO 69 BCL2L1 BCL2L1 BCL2L1 16904 -0.0352 0.0481 NO 70 FADD FADD FADD 17553 -0.0426 0.0384 NO 71 PRKACA PRKACA PRKACA 17802 -0.0462 0.0514 NO 72 CSF2RB CSF2RB CSF2RB 18469 -0.0611 0.0512 NO aSignal to noise value is used to rank the genes according to their importance in the
actual comparison.
b Running Enrichment Score is calculated by GSEA to find genes contributing to
pathways significance.
cEnrichment score indicates whether the gene is contributing to the significance of the
pathway Yes or No (greyscaled).
32
Downloaded from iovs.arvojournals.org on 09/28/2021
Table S11 – Oxidtive Phosphorylation pathway in comparison H60 vs. C21, downregulated GENE SYMBOL DESC LIST LOC S2Na RESb CORE_ENRICHMENTc 1 NDUFB10 NDUFB10 NDUFB10 19313 -0.135 0.0077 YES 2 NDUFB8 NDUFB8 NDUFB8 19304 -0.133 -0.0151 YES 3 NDUFB9 NDUFB9 NDUFB9 19298 -0.13 -0.0376 YES 4 SDHB SDHB SDHB 19283 -0.127 -0.0591 YES 5 COX5A COX5A COX5A 19257 -0.123 -0.0797 YES 6 UQCRQ UQCRQ UQCRQ 19241 -0.12 -0.1 YES 7 NDUFA7 NDUFA7 NDUFA7 19232 -0.118 -0.12 YES 8 NDUFA6 NDUFA6 NDUFA6 19203 -0.115 -0.139 YES 9 COX6A1 COX6A1 COX6A1 19088 -0.102 -0.153 YES 10 NDUFA1 NDUFA1 NDUFA1 19054 -0.0995 -0.169 YES 11 PPA2 PPA2 PPA2 19044 -0.099 -0.185 YES 12 NDUFB3 NDUFB3 NDUFB3 19041 -0.0987 -0.202 YES 13 ATP5E ATP5E ATP5E 19032 -0.0983 -0.219 YES 14 COX7A1 COX7A1 COX7A1 19000 -0.0961 -0.234 YES 15 UQCRFS1 UQCRFS1 UQCRFS1 18989 -0.0955 -0.25 YES 16 PPA1 PPA1 PPA1 18972 -0.0937 -0.266 YES 17 COX17 COX17 COX17 18944 -0.0921 -0.28 YES 18 NDUFA5 NDUFA5 NDUFA5 18943 -0.0919 -0.296 YES 19 NDUFS6 NDUFS6 NDUFS6 18893 -0.0891 -0.309 YES 20 ATP5O ATP5O ATP5O 18860 -0.0871 -0.323 YES 21 NDUFA2 NDUFA2 NDUFA2 18799 -0.0843 -0.335 YES 22 NDUFS3 NDUFS3 NDUFS3 18719 -0.081 -0.345 YES 23 NDUFB6 NDUFB6 NDUFB6 18648 -0.0782 -0.356 YES 24 NDUFA11 NDUFA11 NDUFA11 18641 -0.078 -0.369 YES 25 COX7B COX7B COX7B 18578 -0.0757 -0.379 YES 26 NDUFA8 NDUFA8 NDUFA8 18576 -0.0756 -0.392 YES 27 COX8A COX8A COX8A 18558 -0.0749 -0.404 YES 28 NDUFB5 NDUFB5 NDUFB5 18488 -0.0726 -0.413 YES 29 COX6B1 COX6B1 COX6B1 18483 -0.0725 -0.426 YES 30 NDUFV2 NDUFV2 NDUFV2 18348 -0.0683 -0.431 YES 31 NDUFB2 NDUFB2 NDUFB2 18331 -0.0678 -0.442 YES 32 NDUFB11 NDUFB11 NDUFB11 18277 -0.0666 -0.451 YES 33 ATP5F1 ATP5F1 ATP5F1 18273 -0.0665 -0.462 YES 34 ATP5J2 ATP5J2 ATP5J2 18249 -0.0657 -0.472 YES 35 COX4I1 COX4I1 COX4I1 18213 -0.0649 -0.482 YES 36 ATP5G3 ATP5G3 ATP5G3 18123 -0.0626 -0.488 YES 37 NDUFV3 NDUFV3 NDUFV3 17792 -0.0567 -0.482 YES 38 NDUFV1 NDUFV1 NDUFV1 17734 -0.0558 -0.489 YES 39 NDUFS5 NDUFS5 NDUFS5 17731 -0.0557 -0.498 YES 40 NDUFA4 NDUFA4 NDUFA4 17718 -0.0554 -0.507 YES 41 NDUFA12 NDUFA12 NDUFA12 17663 -0.0543 -0.514 YES 42 COX7C COX7C COX7C 17616 -0.0535 -0.521 YES
33
Downloaded from iovs.arvojournals.org on 09/28/2021 43 CYC1 CYC1 CYC1 17573 -0.0529 -0.528 YES 44 ATP5H ATP5H ATP5H 17544 -0.0525 -0.536 YES 45 NDUFA9 NDUFA9 NDUFA9 17447 -0.0511 -0.54 YES 46 ATP5G1 ATP5G1 ATP5G1 17380 -0.05 -0.545 YES 47 NDUFB4 NDUFB4 NDUFB4 17008 -0.0446 -0.534 YES 48 COX6A2 COX6A2 COX6A2 16925 -0.0435 -0.538 YES 49 ATP5J ATP5J ATP5J 16809 -0.0421 -0.539 YES 50 COX5B COX5B COX5B 16791 -0.0419 -0.546 YES 51 ATP6V1H ATP6V1H ATP6V1H 16762 -0.0416 -0.552 YES 52 NDUFB7 NDUFB7 NDUFB7 16718 -0.0412 -0.556 YES 53 NDUFA13 NDUFA13 NDUFA13 16581 -0.0397 -0.557 YES 54 ATP5D ATP5D ATP5D 16558 -0.0394 -0.562 YES 55 ATP6V1E1 ATP6V1E1 ATP6V1E1 16552 -0.0394 -0.569 YES 56 COX7A2 COX7A2 COX7A2 16522 -0.0392 -0.574 YES 57 COX6B2 COX6B2 COX6B2 16134 -0.0353 -0.561 NO 58 NDUFC1 NDUFC1 NDUFC1 16050 -0.0346 -0.562 NO 59 SDHD SDHD SDHD 16022 -0.0343 -0.567 NO 60 NDUFA3 NDUFA3 NDUFA3 15314 -0.0281 -0.536 NO 61 NDUFC2 NDUFC2 NDUFC2 15135 -0.0269 -0.532 NO 62 UQCRH UQCRH UQCRH 15024 -0.026 -0.531 NO 63 ATP6V1E2 ATP6V1E2 ATP6V1E2 14984 -0.0257 -0.533 NO 64 UQCRB UQCRB UQCRB 14981 -0.0257 -0.538 NO 65 UQCRC1 UQCRC1 UQCRC1 14918 -0.0252 -0.539 NO 66 NDUFS7 NDUFS7 NDUFS7 14674 -0.0234 -0.531 NO 67 NDUFA10 NDUFA10 NDUFA10 14630 -0.023 -0.533 NO 68 NDUFS8 NDUFS8 NDUFS8 14387 -0.0212 -0.524 NO 69 SDHA SDHA SDHA 14192 -0.0198 -0.518 NO 70 ATP5A1 ATP5A1 ATP5A1 14064 -0.0189 -0.514 NO 71 ATP6V1F ATP6V1F ATP6V1F 14019 -0.0186 -0.515 NO 72 ATP5C1 ATP5C1 ATP5C1 13711 -0.0165 -0.503 NO 73 COX6C COX6C COX6C 13354 -0.0139 -0.487 NO 74 ATP5B ATP5B ATP5B 12813 -0.0108 -0.462 NO 75 ATP6V1D ATP6V1D ATP6V1D 12745 -0.0104 -0.46 NO 76 ATP6V1B1 ATP6V1B1 ATP6V1B1 12561 -0.00931 -0.452 NO 77 SDHC SDHC SDHC 12330 -0.00786 -0.442 NO 78 UQCRC2 UQCRC2 UQCRC2 11827 -0.00515 -0.418 NO 79 ATP6V0A2 ATP6V0A2 ATP6V0A2 11606 -0.00395 -0.407 NO 80 NDUFS2 NDUFS2 NDUFS2 11461 -0.00329 -0.4 NO 81 ATP6V0B ATP6V0B ATP6V0B 11439 -0.00314 -0.4 NO 82 NDUFS1 NDUFS1 NDUFS1 9986 0.00441 -0.325 NO 83 COX8C COX8C COX8C 9379 0.00765 -0.295 NO 84 ATP4B ATP4B ATP4B 8883 0.0102 -0.27 NO 85 ATP6V1C1 ATP6V1C1 ATP6V1C1 7552 0.0171 -0.204 NO 86 NDUFS4 NDUFS4 NDUFS4 7088 0.0193 -0.183 NO 87 ATP6V1G2 ATP6V1G2 ATP6V1G2 6613 0.022 -0.161 NO 88 ATP6V1B2 ATP6V1B2 ATP6V1B2 5904 0.0256 -0.129 NO
34
Downloaded from iovs.arvojournals.org on 09/28/2021 89 ATP6V1C2 ATP6V1C2 ATP6V1C2 5305 0.0291 -0.102 NO 90 ATP4A ATP4A ATP4A 4338 0.0352 -0.0572 NO 91 ATP12A ATP12A ATP12A 4160 0.0364 -0.0541 NO 92 ATP6V0A4 ATP6V0A4 ATP6V0A4 4112 0.0367 -0.0579 NO 93 ATP6V0D1 ATP6V0D1 ATP6V0D1 3788 0.0389 -0.0475 NO 94 ATP6AP1 ATP6AP1 ATP6AP1 3702 0.0396 -0.0498 NO 95 TCIRG1 TCIRG1 TCIRG1 3575 0.0407 -0.0501 NO 96 COX10 COX10 COX10 3073 0.0448 -0.0312 NO 97 ATP6V1A ATP6V1A ATP6V1A 3049 0.045 -0.0377 NO 98 COX7B2 COX7B2 COX7B2 2451 0.0507 -0.0146 NO 99 COX4I2 COX4I2 COX4I2 1782 0.0585 0.0112 NO 100 COX15 COX15 COX15 1641 0.0606 0.00839 NO 101 ATP6V1G3 ATP6V1G3 ATP6V1G3 1331 0.0656 0.0139 NO 102 ATP6V0A1 ATP6V0A1 ATP6V0A1 1236 0.0676 0.00754 NO 103 NDUFA4L2 NDUFA4L2 NDUFA4L2 818 0.0782 0.0175 NO 104 ATP6V0D2 ATP6V0D2 ATP6V0D2 8 0.269 0.0458 NO aSignal to noise value is used to rank the genes according to their importance in the
actual comparison.
b Running Enrichment Score is calculated by GSEA to find genes contributing to
pathways significance.
cEnrichment score indicates whether the gene is contributing to the significance of the
pathway Yes or No (greyscaled).
35
Downloaded from iovs.arvojournals.org on 09/28/2021 Table S12 – TGF-beta Signaling Pathway in comparison H60 vs. H21, upregulated GENE SYMBOL DESC LIST LOC S2Na RESb CORE_ENRICHMENTc 1 BMP5 BMP5 BMP5 19407 -0.154 0.00284 YES 2 INHBA INHBA INHBA 19275 -0.113 -0.042 YES 3 SMAD7 SMAD7 SMAD7 19029 -0.0914 -0.0674 YES 4 THBS2 THBS2 THBS2 18881 -0.085 -0.0905 YES 5 PPP2R1B PPP2R1B PPP2R1B 18825 -0.0823 -0.116 YES 6 TGFB3 TGFB3 TGFB3 18181 -0.0651 -0.111 YES 7 AMHR2 AMHR2 AMHR2 18152 -0.0645 -0.131 YES 8 RBL1 RBL1 RBL1 18062 -0.0633 -0.148 YES 9 IFNG IFNG IFNG 18017 -0.0627 -0.167 YES 10 PITX2 PITX2 PITX2 17946 -0.0615 -0.184 YES 11 PPP2R1A PPP2R1A PPP2R1A 17684 -0.0578 -0.192 YES 12 TGFBR1 TGFBR1 TGFBR1 17575 -0.0561 -0.205 YES 13 SMAD5 SMAD5 SMAD5 17520 -0.0554 -0.221 YES 14 LTBP1 LTBP1 LTBP1 17432 -0.0542 -0.236 YES 15 BMPR1B BMPR1B BMPR1B 17380 -0.0535 -0.251 YES 16 BMP4 BMP4 BMP4 17174 -0.0512 -0.258 YES 17 BMPR2 BMPR2 BMPR2 16785 -0.0471 -0.256 YES 18 TGFB2 TGFB2 TGFB2 16677 -0.0462 -0.266 YES 19 SMAD6 SMAD6 SMAD6 16580 -0.0453 -0.276 YES 20 TGFB1 TGFB1 TGFB1 16290 -0.0427 -0.277 YES 21 E2F4 E2F4 E2F4 16244 -0.0422 -0.289 YES 22 BMP2 BMP2 BMP2 16202 -0.0419 -0.301 YES 23 THBS4 THBS4 THBS4 16126 -0.0413 -0.311 YES 24 ROCK2 ROCK2 ROCK2 16114 -0.0412 -0.324 YES 25 BMP8A BMP8A BMP8A 15996 -0.0402 -0.332 YES 26 RBL2 RBL2 RBL2 15904 -0.0394 -0.341 YES 27 ACVR2A ACVR2A ACVR2A 15832 -0.039 -0.35 YES 28 EP300 EP300 EP300 15733 -0.0383 -0.358 YES 29 INHBB INHBB INHBB 15682 -0.0379 -0.369 YES 30 INHBE INHBE INHBE 15491 -0.0365 -0.372 YES 31 THBS1 THBS1 THBS1 15387 -0.0358 -0.378 YES 32 TGFBR2 TGFBR2 TGFBR2 14845 -0.0323 -0.363 NO 33 CREBBP CREBBP CREBBP 14743 -0.0315 -0.368 NO 34 LEFTY2 LEFTY2 LEFTY2 14239 -0.0283 -0.353 NO 35 COMP COMP COMP 13434 -0.0236 -0.321 NO 36 SMAD3 SMAD3 SMAD3 13332 -0.0231 -0.323 NO 37 ACVR1 ACVR1 ACVR1 13294 -0.023 -0.329 NO 38 DCN DCN DCN 13096 -0.0218 -0.327 NO 39 RPS6KB2 RPS6KB2 RPS6KB2 13077 -0.0217 -0.333 NO 40 BMP6 BMP6 BMP6 12985 -0.0212 -0.336 NO 41 THBS3 THBS3 THBS3 12862 -0.0206 -0.337 NO 42 PPP2CA PPP2CA PPP2CA 12853 -0.0205 -0.343 NO 43 CDKN2B CDKN2B CDKN2B 12852 -0.0205 -0.35 NO 44 NODAL NODAL NODAL 12828 -0.0204 -0.356 NO
36
Downloaded from iovs.arvojournals.org on 09/28/2021 45 SMAD4 SMAD4 SMAD4 12573 -0.0191 -0.35 NO 46 ZFYVE16 ZFYVE16 ZFYVE16 12544 -0.0189 -0.354 NO 47 SP1 SP1 SP1 12519 -0.0188 -0.36 NO 48 SMURF2 SMURF2 SMURF2 12489 -0.0186 -0.364 NO 49 TNF TNF TNF 12429 -0.0183 -0.368 NO 50 BMPR1A BMPR1A BMPR1A 12323 -0.0178 -0.368 NO 51 CHRD CHRD CHRD 12279 -0.0175 -0.372 NO 52 MAPK1 MAPK1 MAPK1 11746 -0.0147 -0.35 NO 53 RHOA RHOA RHOA 11489 -0.0133 -0.342 NO 54 ROCK1 ROCK1 ROCK1 11415 -0.0129 -0.343 NO 55 RPS6KB1 RPS6KB1 RPS6KB1 10998 -0.0105 -0.326 NO 56 SMAD9 SMAD9 SMAD9 10985 -0.0104 -0.329 NO 57 ACVR2B ACVR2B ACVR2B 10845 -0.00963 -0.325 NO 58 TFDP1 TFDP1 TFDP1 10817 -0.00954 -0.327 NO 59 ZFYVE9 ZFYVE9 ZFYVE9 10615 -0.00859 -0.32 NO 60 ACVRL1 ACVRL1 ACVRL1 10356 -0.00727 -0.309 NO 61 NOG NOG NOG 10254 -0.00675 -0.306 NO 62 GDF5 GDF5 GDF5 10115 -0.006 -0.302 NO 63 BMP8B BMP8B BMP8B 9589 -0.00332 -0.276 NO 64 ID1 ID1 ID1 9483 -0.00278 -0.272 NO 65 E2F5 E2F5 E2F5 9380 -0.00222 -0.268 NO - 66 SMAD1 SMAD1 SMAD1 9132 0.000934 -0.256 NO 67 SMAD2 SMAD2 SMAD2 8153 0.00423 -0.206 NO 68 ID4 ID4 ID4 7705 0.0068 -0.184 NO 69 BMP7 BMP7 BMP7 7647 0.00722 -0.183 NO 70 SMURF1 SMURF1 SMURF1 7584 0.00755 -0.183 NO 71 MAPK3 MAPK3 MAPK3 7017 0.0109 -0.156 NO 72 GDF7 GDF7 GDF7 6823 0.0119 -0.15 NO 73 PPP2R2B PPP2R2B PPP2R2B 6555 0.0134 -0.14 NO 74 ACVR1C ACVR1C ACVR1C 5804 0.0179 -0.106 NO 75 PPP2CB PPP2CB PPP2CB 5031 0.0232 -0.0718 NO 76 CUL1 CUL1 CUL1 5021 0.0233 -0.0791 NO 77 GDF6 GDF6 GDF6 4591 0.0265 -0.0647 NO 78 FST FST FST 4389 0.0279 -0.0632 NO 79 RBX1 RBX1 RBX1 4165 0.0299 -0.0611 NO 80 INHBC INHBC INHBC 3991 0.0316 -0.0622 NO 81 PPP2R2A PPP2R2A PPP2R2A 3430 0.0367 -0.0439 NO 82 MYC MYC MYC 3190 0.0394 -0.0439 NO 83 ACVR1B ACVR1B ACVR1B 3158 0.0397 -0.0555 NO 84 ID3 ID3 ID3 2831 0.0434 -0.052 NO 85 ID2 ID2 ID2 2788 0.044 -0.0644 NO 86 PPP2R2C PPP2R2C PPP2R2C 2517 0.0475 -0.0652 NO 87 AMH AMH AMH 2399 0.049 -0.0751 NO 88 LEFTY1 LEFTY1 LEFTY1 660 0.0959 -0.00184 NO
37
Downloaded from iovs.arvojournals.org on 09/28/2021 aSignal to noise value is used to rank the genes according to their importance in the
actual comparison.
b Running Enrichment Score is calculated by GSEA to find genes contributing to
pathways significance.
cEnrichment score indicates whether the gene is contributing to the significance of the
pathway Yes or No (greyscaled).
38
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