Nature - USA (2020-09-24)

0.00.5 1.01.5 2.0

0

2

4

6

Av

erage -log10

p

OVCAR- 8

PEX 1 PEX^7

AGPS

PEX 3

AGPAT6

0.00.5 1.01.5 2.02.5

0

1

2

3

4

5

OVCAR- 8

PEX1

AGPSAGPAT3

PEX1 0

0 246810

0

2

4

6

8

10

786-O

(4 days)

TMEM30A

FAR1

AGPS

GNPAT

PEX3

PEX1

PEX1 0

AGPAT3

02468

0

2

4

6

8

10

786-O

(6 days)

Peroxisome genes

AGPS

FAR1

GNPEX19PAT

PEXPEX 27

PEX16PEX10

PEX12

PEX 5

PEX 3 PEX13

Lipid synthesis

AGPAT3

SMG7SMG 9

STEAP3

HMBS B3GALT5 MBOAT7

AGPAT 3 ACSL^4

TFRC FAR1 FADS2

ANTXR1

AGPS GNPAT

PEX10

PEX7 PEX2

PEX1PEX3 2

PEX5 NR2F2

PEX1 9

PEX16FOSL1

CITED1

MED12 EP300

CRYBB1

KAT2A

DLST

TADA2B

OGDH

EPAS1

ATXN7L 3

PSMD4PSMD3

ADRM1

Peroxisomal lipid metabolism module

HIF- 2 module

786-O hits

KEAP1

a b

AGPS PEX12

PEX1 0 PEX1

FAR1

PEX1 9 PEX3

ABCD3 (^33333333) UCK1
RCAN3
MAAEBP2F JARID2
ACSL4 CUL3
AHR
LPCAT3 KEAP1
AGPAT6
TXNRD1
AGPAT 3 XDH
TCEA1 CALR
TCEB3
HSP90B1
MLLT1
OVCAR-8 hits
Peroxisomal lipid
metabolism module
c
d
geneSet overlapp-Value q-Value
KEGG_PEROXISOME 12 1757 .34E-1 43 .47E-1 0
REACTOME_ABCA_TRANSPORTERS_IN_LIPID_HOMEOSTASIS2 30 9.87E-0 82 .33E-0 4
WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D8 3592 .21E-0 73 .49E-0 4
LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_LARGE_VS_TINY_DN 0363 .75E-0 74 .44E-0 4
REACTOME_PEROXISOMAL_LIPID_METABOLISM 3306 .26E-0 65 .92E-0 3
REACTOME_ABC_FAMILY_PROTEINS_MEDIATED_TRANSPORT2 32 1.32E-0 58 .96E-0 3
ZHENG_RESPONSE_TO_ARSENITE_U2P2 41 .33E-0 58 .96E-0 3
PID_HIF2PATHWAY 3772 .23E-0 51 .18E-0 2
GENTILE_UV_RESPONSE_CLUSTER_D 740 02 .25E-0 51 .18E-0 2
nConnection
Pathways enriched in the top hits from the 786-O CRISPR screen
Average log 2 (RSL3 / DMSO) Average log 2 (RSL3 / DMSO) Average log 2 (ML210 / DMSO) Average log 2 (ML210 / DMSO)
e
A
B
C
D
network
gene list
gene sets
A–8 connections
B –1 connection
C –2 connections
D –0 connections
Principle of Gen e- List N etwork E nrichment A nalysis (GeLiNEA)
GeneSetvOerlapnConnectionsp- value
KEGG_Peroxisome 8884 .41E-08
REACTOME_Peroxisomal lipid metabolism 2191 .14E-05
REACTOME_ABCAtransporters in lipid homeostasis 2176 .78E-05
REACTOME_Triglyceride biosynthesis 3423 .40E-04
CLAUS_PGR positive meningioma_up 04 1.19E-03
Pathways enriched in the top hits from the OVCAR-8 screen
q- value
2.08E-4
2.70E-2
1.07E-1
4.03E-1
7.56E-1
786-O
154
OVCAR-8
42
12
ACSL4
KEAP1
PEX1 0
AGPAT3
AGPS
TMEM164
LPCAT3
FAR1
PEX3
PEX1
SMG9
MMD
g
f
(4 days) (8 days)
Extended Data Fig. 1 | See next page for caption.