Table 2 Enriched Pathways Significantly Altered during Recovery from Form-deprivation (FDMR). GSEA was used to identify pathways (KEGG, Reactome, STKE and PID) significantly altered between recovery time-points 6 h and 24 h, compared to 0 h using the Signal2Noise metric. Gene expression changes at 6 h compared to 0 h were associated with suppression in cone receptor phototransduction. The period between 6 and 24 h post occluder removal was mainly associated with changes in mitochondrial metabolism and other metabolic pathways. Pathways significantly altered after 24 h recovery compared to 0 h involves a range of cellular processes. ES, enrichment score; NES, normalised enrichment score; FDR, false discovery rate.

From: RNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia

Pathway	Database	Total # Genes Measured	# Genes contributing to ES	Genes contributing to ES	ES	NES	FDR
FDMR_6 h versus FDMR_0 h
Cone Pathway	PID	18	14	RGS9, CNGB3, SLC24A2, PDE6C, GUCA1C, RGS9BP, LRAT, GUCA1A, GRK7, ARR3, CNGA3	− 0.79	− 2.07	0.005
FDMR_24 h versus FDMR_6 h
Cone Pathway	PID	18	14	ARR3, LRAT, GUCA1C, GUCA1A, GRK7, CNGA3, RDH5, RGS9BP, PDE6C, RGS9, GUCY2F, PDE6H, CNGB3, SLC24A2	0.74	2.03	0.02
Respiratory Electron Transport^≠	Reactome	46	17	NDUFS5, NDUFS7, NDUFA1, NDUFS8, NDUFV1, NDUFB4, SDHC, NDUFB6, COX6A1, UQCRH, NDUFV3, NDUFB10, NDUFS2, NDUFB9, NDUFB8, COX6C, NDUFB1	0.58	2	0.03
Iron Uptake and Transport	Reactome	28	8	ABCG2, ATP6V0E1, SLC40A1, TF, ATP6V1H, STEAP3, CP, ATP6V1C2	− 0.61	− 2.03	0.04
Respiratory Electron Transport ATP Synthesis by Chemiosmotic Coupling and Heat Production by Uncoupling Proteins^≠	Reactome	55	20	NDUFS5, NDUFS7, ATP5B, NDUFA1, NDUFS8, NDUFV1, NDUFB4, SDHC, NDUFB6, COX6A1, UQCRH, NDUFV3, NDUFB10, NDUFS2, NDUFB9, NDUFB8, ATP5D, ATP5H, COX6C, NDUFB1	0.55	1.94	0.04
Synthesis of PA	Reactome	17	7	PLA2G10, AGPAT9, AGPAT3, AGPAT2, PLA2G4A, PLA2G12A, GPD1	− 0.69	− 1.98	0.05
Citric Acid Cycle/TCA Cycle^≠	Reactome	18	6	IDH2, OGDH, IDH3G, CS, SDHC, IDH3B	0.69	1.91	0.05
Triglyceride Biosynthesis^≠	Reactome	31	11	DGAT2, AGPAT9, ACSL1, ELOVL2, GPD1, ACSL4, ACSL3, ELOVL7, LPIN1, AGPAT2, AGPAT3	− 0.6	− 2.06	0.06
Intrinsic Pathway	Biocarta	15	8	PROC, COL4A2, COL4A1, COL4A4, COL4A3, F2R, COL4A5, F5	− 0.64	− 1.83	0.23
FDMR_24 h versus FDMR_0 h
Complement Cascade^≠	Reactome	16	8	C1QB, CRP, C1QA, C7, PROS1, CFI, MASP1, C2	0.78	2.18	0.004
Glucagon Type Ligand Receptors^≠	Reactome	21	8	GLP1R, GHRHR, ADCYAP1, GNGT2, GHRH, GCG, VIP, GNG11	0.69	2.09	0.01
Smooth Muscle Contraction	Reactome	16	6	ACTA2, CALD1, LMOD1, MYH11, VCL, MYLK	− 0.72	− 2	0.04
NFkB Pathway^≠	Biocarta	18	7	NFKBIA, IL1R1, TNFAIP3, RIPK1, TAB1, TNFRSF1B, TNFRSF1A	− 0.72	− 2.05	0.05
Histidine Metabolism	KEGG	20	12	ALDH1A3, HAL, MAOB, UROC1, MAOA, METTL6, LCMT2, TRMT11, HNMT, ASPA, LCMT1, CNDP1	− 0.65	− 1.95	0.07
TNFR2 Pathway^≠	Biocarta	15	4	NFKBIA, TNFAIP3, RIPK1, TNFRSF1B	− 0.71	− 1.9	0.09
Transferrin Endocytosis and Recycling	Reactome	17	4	STEAP3, TF, ATP6V1H, ATP6V1C2	− 0.64	− 1.81	0.12
Iron Uptake and Transport	Reactome	28	7	STEAP3, SLC46A1, TF, ATP6V1H, CP, ABCG2, ATP6V1C2	− 0.58	− 1.86	0.12
Caspase Pathway^≠	PID	42	12	CASP9, DFFB, ACTA1, DFFA, GSN, CRADD, CASP10, TRADD, ARHGDIB, CASP2, RIPK1, TNFRSF1A	− 0.52	− 1.81	0.12
Apoptosis^≠	KEGG	59	24	NTRK1, DFFB, DFFA, IL1R1, TRADD, ENDOD1, TNFRSF10B, CFLAR, IL1RAP, PIK3CB, IRAK4, NGF, TNFRSF1A, CASP9, NFKBIA, PPP3CA, PPP3R1, CASP10, CASP3, PRKAR2A, CAPN2, TNFSF10, RIPK1, CAPN1	− 0.49	− 1.83	0.13
HIV/NEF Pathway	PID	29	13	DFFB, DFFA, CRADD, TRADD, CFLAR, TNFRSF1A, CASP9, NFKBIA, CASP3, CASP2, RIPK1, CD247, MAP3K5	− 0.55	− 1.78	0.13
HIV/NEF Pathway^≠	Biocarta	47	13	DFFB, DFFA, GSN, CRADD, TRADD, PRKCD, TNFRSF1B, TNFRSF1A, CASP9, NFKBIA, ARHGDIB, CASP2, RIPK1	− 0.51	− 1.82	0.13
Death Pathway^≠	Biocarta	27	9	CASP9, NFKBIA, DFFB, DFFA, CASP10, TRADD, TNFSF10, TNFRSF10B, RIPK1	− 0.55	− 1.75	0.16
Muscle Contraction	Reactome	30	9	ACTA2, DES, MYL1, CALD1, TNNC1, LMOD1, MYH11, VCL, MYLK	− 0.54	− 1.74	0.18
Nucleotide Binding Domain Leucine Rich Repeat Containing Receptor NLR Signaling Pathways	Reactome	31	10	PANX1, CASP9, P2RX7, MAPK11, RIPK2, CARD9, CASP2, TNFAIP3, NOD1, TAB1	− 0.53	− 1.7	0.19
Amino Acid Transport Across the Plasma Membrane	Reactome	19	7	SLC7A6, SLC7A9, SLC6A14, SLC16A10, SLC7A11, SLC38A2, SLC7A2	− 0.59	− 1.72	0.19
WNT Ca2 Cyclic GMP Pathway	STKE	17	5	TF, ITPR2, PDE6C, PDE6B, ITPR3	− 0.6	− 1.7	0.19
Retinol Metabolism^≠	KEGG	17	6	RDH8, ALDH1A2, ALDH1A1, RDH5, DHRS3, BCMO1	0.67	1.88	0.19
NOD1/2 Signaling Pathway	Reactome	23	8	CASP9, MAPK11, RIPK2, CARD9, CASP2, TNFAIP3, NOD1, TAB1	− 0.56	− 1.69	0.2
ALK Pathway	Biocarta	26	6	BMP4, NPPB, FZD1, BMP2, SMAD6, BMP7	0.58	1.83	0.2
Intrinsic Pathway	Biocarta	15	7	F10, COL4A2, COL4A1, COL4A4, COL4A3, F2R, F5	− 0.63	− 1.7	0.21
Prion Diseases^≠	KEGG	23	7	C1QB, C1QA, STIP1, IL6, NOTCH1, C7, HSPA5	0.62	1.84	0.23
Glypican 1 pathway	PID	23	8	LYN, HCK, TGFB2, YES1, FLT1, SRC, TGFB3, FGF2	− 0.54	− 1.66	0.24
NFkB Canonical Pathway	PID	18	5	NFKBIA, RIPK2, TNFAIP3, BCL10, TNFRSF1A	− 0.6	− 1.65	0.24

Note: pairwise comparisons with control animals (ie 6 h vs control and 12 h vs control) can be found in Supplementary Table 6.
NOTE: + NES = expression upregulated;—NES = expression downregulated; ^≠present in GSEA using Pearson’s correlation metric (Supplementary Table 7); *present in previous data⁷⁰.

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