In vitro steroid profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
NCI-H295R cells were incubated in 6-well plates in 1 ml of serum-free DMEM/Ham’s F-12
medium (Gibco, Thermo Fisher), supplemented with 1% penicillin-streptomycin and 1% ITS universal
cell culture premix. Serum-free media was used, as serum itself contains steroids which may confound
results. Media was collected after 48-hour incubation in silanized glass tubes and stored at -20℃. To
extract steroids from the media, 20 ul of serum steroid internal standard solution was transferred to each
tube, followed by 3 ml Methyl tert-butyl ether (MTBE, Sigma-Aldrich). After vortexing, samples were
frozen at -20℃ for at least 1 hour. The top layer (liquid phase) was transferred to a 96-well plate using
Pasteur pipettes. MTBE was evaporated to dryness at 55℃ and samples were reconstituted in 125 ul of
1:1 H2O/methanol. Steroid metabolites were identified and quantified by LC-MS/MS, with reference to
a linear calibration series and appropriate internal standards as described previously (AcquityTM Ultra
Performance Liquid Chromatographer, Xevo TQ Mass Spectrometer) (1, 2).
RNA sequencing - NCI-H295R NNT knockdown models
RNA samples from KD siRNA, SCR SiRNA (72 hours post-transfection), KD shRNA and
SCR shRNA cells (in triplicates) were prepared using the RNeasy Mini kit (Qiagen). NNT protein knock-
down was confirmed independently by Western Blotting. Libraries were generated using the TruSeq
Stranded mRNA Library Prep Kit (Illumina).
RNA was quantified using Qubit® RNA BR Assay Kit and if necessary diluted to 25-100 ng
in 12.5 ul. This was followed by RNA quality check to establish the RIN (RNA Integrity Number) using
the Agilent RNA ScreenTape system. RNA was then processed on the automated Illumina Neoprep
system following the Library prep TruSeq Stranded mRNA Library Prep Kit for NeoPrep. Libraries were
normalized to 10 nM by the Neoprep.
Each library quantity was checked again using Qubit DNA HS Assay Kit and 2 ul of each
library were pooled together into a single tube. This pool of 16 samples was checked on the Agilent
High Sensitivity D1000 ScreenTape to ensure the libraries were the correct size at 300 bp. The pooled
sample was diluted to 4 nM. The 4 nM library (containing the 16 pooled libraries) was sequenced on a
NextSeq500 using a NextSeq® 500/550 High Output Kit v2 (150 cycles) with a 1% PhiX control spiked
in.
Data Quality control was performed with FastQC v0.11.4 (RRID:SCR_014583), revealing
no appreciable technical biases. RNA-seq reads were mapped to the human genome (hg19, UCSC
annotation) using STAR software v2.4.2a (RRID:SCR_015899) (3) supplied with default parameters.
Counts per gene were calculated using the htseq-count tool from the HTSeq v0.6.1p1 package
(RRID:SCR_005514) (4) with the following parameters: — format=bam — minaqual=10 —
stranded=reverse — mode=union. Differentially expressed genes were identified using the DESeq2
v1.14.1 package (RRID:SCR_015687) (5) from Bioconductor release 3.3. Differentially expressed genes
were called at a false discovery rate of 5%. Adjusted p-values for the KD-shRNA vs SCR-shRNA
pairwise comparison were re-calculated using fdrtool (6). Pathway Analysis was carried out using GAGE
(7) v2.22 package from Bioconductor release 3.3, referencing KEGG pathways (RRID:SCR_012773)
and assessing gene sets towards both single directions (up-/down-regulated) and both directions
simultaneously (bi-directional). Differentially regulated pathways were called at a p value of <0.01. The
accession number for the raw and processed data files for the RNA sequencing analysis reported in this
paper is NCBI GEO: GSE106873.
RNA sequencing - mouse adrenals
Aligned BAM files from Meimaridou et al (8) were used to determine counts per gene using
custom scripts acting in a HTSeq-count (RRID:SCR_005514) (4) compatible mode with the following
parameters: — format=bam — minaqual=10 — stranded=reverse — mode=union. Gene counts were analysed
using DESeq2 (v1.14.1) (RRID:SCR_015687) (6) package from Bioconductor release 3.4, and pathway
analysis was carried out using GAGE (7) v2.24, referencing KEGG pathways (RRID:SCR_012773) and
assessing gene sets towards both single directions (up-/down-regulated) and both directions
simultaneously (bi-directional). Differentially regulated pathways were called at a false discovery rate
(q-value) of < 0.05.
Whole metabolome analysis
Metabolism was quenched in a) KD siRNA and SCR siRNA cells growing in 6-well plates,
96 hours after cell loading and 72 hours after siRNA transfection and b) KD shRNA and SCR shRNA
cells, 96 hours after cell loading. Six biological replicates were used per cell group, each consisting of
two wells. 200 ul of media from each well were collected and frozen, followed by media removal and
washes with three aliquots of Phosphate-Buffered Saline. Following this, 0.9 ml of a 40/40/20% solution
of acetonitrile, methanol and water (Sigma-Aldrich) at a temperature of approximately -40℃ was added
to each well and plates were frozen at -80℃ for 15 min. Cells were scraped off the wells and the
suspension was centrifuged at 12,000 rpm (4℃) for 10 min to separate the extraction supernatant from
cell pellet. The extraction supernatant was dried applying a vacuum centrifugal evaporator (Thermo
Scientific Savant SPD111V speedvac concentrator coupled to a Savant RVT5105 vapour trap). 100 ul
of media samples were dried applying the same process. Pooled QC samples were prepared for cell media
analysis (by pooling of 100 ul aliquots of all biological samples) and cell extract analysis (by pooling of
200 ul aliquots of all cell extract samples).
Samples were analysed applying ultra-performance liquid chromatography-mass
spectrometry (UPLC-MS) using a Thermo Scientific Ultimate3000 UPLC system coupled to an
electrospray Q Exactive Focus mass spectrometer. Two assays were applied to increase the number of
metabolites detected, a HILIC assay to investigate water-soluble metabolites and a C18 reversed phase
method to investigate lipid metabolites.
The HILIC method applied a Thermo Scientific Accucore 150 Amide HILIC column (100 x
2.1mm, 2.6 um) operated at a temperature of 35℃ and a flow rate of 500 uL.min-1. Solvent A was A 10
mM Ammonium Formate in 95% Acetonitrile/5% water + 0.1% formic acid and solvent B was 10 mM
Ammonium Formate in 50% Acetonitrile/50% water + 0.1% formic acid. The gradient elution was
applied at follows; Start at 99%A for 1 minute, followed by decreases to 85% and 50% at 3 minutes and
6 minutes with a curve of 5 and then a decrease to 5% A at 9 minutes and an increase to 99% A at 10.5
minutes with a curve of 5. The total analysis time was 15 minutes and the injection volume was 2uL.
Mass spectral data was collected in positive and negative ion modes separately at a mass resolution of
70,000 (FWHM at m/z 200). Data Dependent Analysis data was acquired for three QC samples to aid
metabolite identification. QC samples were analysed 10 times at the start of the run and then after every
6th biological sample with two QC samples analysed after all biological samples had been analysed.
The C18 reversed phase method applied a Thermo Scientific Hypersil GOLD C18 column
(100 x 2.1mm, 1.9 um) operated at a temperature of 55℃ and a flow rate of 400 uL.min-1. Solvent A
was 10 mM Ammonium Formate in 60% Acetonitrile/40% water + 0.1% formic acid and solvent B was
10 mM Ammonium Formate in 90% isopropyl alcohol/10% acetonitrile + 0.1% formic acid. The gradient
elution was applied at follows; Start at 80%A for 0.5 minutes, followed by a decrease to 0% A at 8.5
minutes with a curve of 5 and then an increase to 80% A at 11.5 minutes with a curve of 5. The total
analysis time was 15 minutes and the injection volume was 2uL. Mass spectral data was collected in
positive and negative ion modes separately at a mass resolution of 70,000 (FWHM at m/z 200). QC
samples were analysed 10 times at the start of the run and then after every 6th biological sample with two
QC samples analysed after all biological samples had been analysed.
Raw data was converted to the mzML format applying ProteoWizard and then deconvoluted
applying the software XCMS (9), operated on an office PC in R using previously described parameters
(10). Putative metabolite annotations were provided using the software PUTMEDID_LCMS using a RT
window of +/- 2 seconds and a mass error of 5ppm (11).
The data were filtered for quality based on the QC sample data with metabolites with a
relative standard deviation >20% or detected in less than 60% of the QC samples being removed (12).
Univariate and multivariate data analysis and pathway enrichment analysis were performed in
MetaboAnalyst 3.0 (RRID:SCR_015539) (13). This included Principal Components Analysis (PCA),
Mann Whitney U tests or Kruskal-Wallis tests to identify metabolites demonstrating a statistically
significant change in relative concentrations between two or three biological classes. Fold changes were
calculated by division of the mean peak response for one biological class by the mean peak response of
the second biological class.
Supplementary Tables and Figures
Supplementary Figure 1. A, Western Blotting confirms efficient NNT protein silencing in NCI-H295R cells transfected with anti-NNT siRNA (KD siRNA), 72-166 hours post transfection. B, Real-time PCR confirms effective NNT silencing 72 hours post siRNA transfection in NCI-H295R cells. Two different siRNAs were tried, targeting different sequences on the NNT transcriptome (KD siRNA and KD siRNA2); KD siRNA2 was used to corroborate the effects observed with KD siRNA transfection on proliferation and apoptosis. Cells transfected with scrambled, non-sense siRNA were used as controls (SCR siRNA). *** p<0.001, **** p<0.0001; n≥10. C, Western Blotting confirms NNT protein silencing in NCI-H295R cells transfected with KD shRNA. Cells transfected with scramble, non-sense shRNA were used as controls (SCR shRNA). D, Real-time PCR confirms effective NNT silencing in NCI-H295R cells transfected with shRNA against NNT (KD shRNA). Cells transfected with scrambled, non-sense shRNA were used as controls (SCR shRNA). **** p<0.0001; n≥7.
Supplementary Figure 2. Effect of alternative siRNA against NNT (KD siRNA2) on NCI-H295R cell proliferation and apoptosis rates. A, Proliferation rates observed in siRNA2-transfected NCI-H295R cells, 72-166 h post-transfection. ** p<0.01; n=5 independent experiments. B, Caspase 3/7 activity ratio in KD siRNA2 cells to SCR siRNA-transfected cells, after standardization to cell numbers (120 h post- transfection). * p<0.05; n=5.
A
Proliferation rate
B
Apoptotic rate
150
5.
*
Proliferation rate (%)
Caspase 3/7 activity
ratio to control
100
4-
3.
50-
2-
0
I
**
1-
-50
0
SCR siRNA
T
KD siRNA2
T
SCR siRNA
T
KD SİRNA2
1
Supplementary Table 1. Genetic STR analysis of H295R cells used in this project, including 22 highly polymorphic areas (loci). Number of sequence repeats is indicated for each locus.
Marker
Allele 1
Allele 2
AMEL
x ☒
D3S1358
15
16
D1S1656
12
D2S441
11
D10S1248
14
D13S317
13
Penta E
5
D16S539
11
D18S51
17
D2S1338
25
CSF1PO
10
12
Penta D
8
TH01
9.3
vWA
17
18
D21S11
32.2
D7S820
9
12
D5S818
12
ΤΡΟΧ
8
D8S1179
13
D12S391
19
20
D19S433
13
FGA
19.2
24
D22S1045
15
Supplementary Table 2. Steroidogenic enzyme expression in KD siRNA and SCR siRNA cells, assessed
by Real-Time PCR. Results are expressed as median 4Ct (IQR) values. n27 independent experiments.
StAR: Steroidogenic acute regulatory protein; CYP11A1: Cholesterol side-chain cleaving enzyme;
3HSD2: 3ß-hydroxysteroid dehydrogenase type II; CYP17A1: 17a-hydroxylase- 17/20 lyase;
CYP21A2: 21-hydroxylase
SCR SİRNA median ACt (IQR)
KD SİRNA median ACt (IQR)
p value
Median fold change KD siRNA/ SCR siRNA
StAR
4 (2.3-6.8)
2.2 (1.9-3.0)
0.09
CYP11A1
5.9 (3.3-9.0)
4.8 (3.5-4.9)
0.14
3₿HSD2
8.7 (7.6-10.3)
8 (7.4-8.8)
0.02
2
CYP17A1
2.8 (1.5-5.2)
1.8 (0.7-2.9)
0.03
2.5
CYP21A2
9.3 (4.2-12.9)
6.4 (0.4-9.2)
0.02
11.5
Supplementary table 3. Significant genes that are differentially regulated between KD siRNA and SCR
siRNA cells (A) or between KD shRNA and SCR shRNA cells (B) (RNA sequencing). 17 genes
highlighted in bold font were significantly altered in both comparisons. Positive values denote up-
regulation with NNT knockdown. q<0.05 (False Discovery Rate 5%) was used as the threshold of
statistical significance.
Supplementary Table 3A
Gene
log2 Fold Change KD siRNA Vs SCR siRNA
p value
q value
SLC16A6
1.383218178
1.95971E-15
6.41147E-12
SLC16A9
1.259199322
4.2203E-20
2.96392E-16
ARRDC3
1.103592627
2.28231E-15
6.41147E-12
LOC728175
1.021723337
2.9811E-09
1.39575E-06
GNRHR
0.895911271
7.74013E-12
9.05983E-09
CCNE1
0.788621396
2.81919E-09
1.36546E-06
MAN1A1
0.778872578
5.13273E-07
0.000107603
CTSV
0.758410912
1.66716E-08
5.45459E-06
PPP2R1B
0.715673998
7.21568E-11
5.63063E-08
C1orf141
0.701674984
6.26031E-05
0.00389081
CYP17A1
0.675702613
0.000184861
0.00845784
SPRED2
0.668466019
2.27935E-06
0.00037082
MC2R
0.651355465
0.000228438
0.009723137
TAPT1
0.632443173
3.06564E-15
7.17665E-12
ARSG
0.62590135
0.000294315
0.011328988
GNAI1
0.618791402
9.6579E-07
0.00018841
ZNF678
0.614386714
4.41421E-06
0.000607863
CA2
0.606754247
0.000550892
0.017157034
MTF2
0.599485848
1.75993E-09
9.50767E-07
ARHGAP12
0.599306312
1.02643E-07
2.6736E-05
ZNF763
0.598863323
0.000292769
0.011328988
DPP4
0.593070146
0.000503607
0.016298764
IL23R
0.59226251
0.000539068
0.016964399
ITGA1
0.585001105
0.00086819
0.022658038
ITGB8
0.578320032
0.00090321
0.023192846
MSMO1
0.577036521
8.33654E-05
0.004878958
MET
0.571708587
5.63755E-05
0.003534264
MGAT4A
0.564163158
0.000436759
0.014743703
MACC1
0.560597901
0.002080498
0.039650849
CYP21A2
0.560441003
0.001429487
0.031226397
RGL1
0.560328372
1.58752E-06
0.000282257
NRBF2
0.560125717
1.6267E-05
0.001476118
SULT2A1
0.558771598
0.000370974
0.013225124
IKBKAP
0.555933991
1.5175E-05
0.001420989
NEU1
0.555882407
0.000163965
0.007651324
DUSP4
0.547314248
0.001670006
0.034990186
CITED2
0.54701362
0.000420118
0.014414836
PLK2
0.54415396
0.002344394
0.04270993
PTPMT1
0.544114794
1.60059E-05
0.001469406
E2F2
0.543856464
2.46997E-10
1.73466E-07
PLSCR4
0.542943203
4.89159E-06
0.000662283
MSRB3
0.536027719
4.11192E-09
1.8631E-06
ARL4D
0.535615205
0.000394721
0.013860632
PLLP
0.533817534
0.002906259
0.048770984
LBR
0.530390577
2.82822E-07
6.30559E-05
PDE7B
0.525790885
0.00013728
0.006862053
GPR137C
0.525605479
7.26486E-05
0.004360776
DDX18
0.52061528
3.57513E-10
2.28256E-07
SLC38A2
0.516908523
3.55185E-06
0.000509075
PDCD6
0.516729505
5.67892E-08
1.59532E-05
SLC2A3
0.512212935
0.000184148
0.008452757
DCP2
0.51065777
5.22544E-06
0.000691004
UGCG
0.510430232
0.001532866
0.032921467
FAM178A
0.508057229
0.00060397
0.018166948
SLC38A9
0.506291005
0.000378962
0.013436491
DLC1
0.505975183
2.57228E-05
0.002072238
DRP2
0.502053068
0.002229753
0.041224498
ODC1
0.502018384
4.65752E-05
0.003101868
WEE1
0.496812958
1.16891E-05
0.001190671
C2CD2
0.494506882
0.000234175
0.00981857
MAP2K4
0.49410377
0.000415335
0.014414836
TYW3
0.490052348
2.03923E-06
0.000336977
DNMT3B
0.488671044
0.001850909
0.037030036
ETV1
0.487963762
1.66174E-05
0.001486675
COL15A1
0.483502139
0.000357364
0.012903696
MICU3
0.482772281
0.000120267
0.006303252
TCERG1L
0.482710076
0.002686552
0.046341781
SIX2
0.481735626
0.000614755
0.018411192
AQP11
0.479356148
0.000527492
0.016838998
RBPJ
0.478536856
5.8081E-06
0.000728399
SLC17A5
0.475561228
0.000181465
0.008356893
RFK
0.474934962
9.86232E-06
0.001056074
ZCCHC3
0.474168664
2.34513E-06
0.00037082
DICER1
0.472110682
0.000906736
0.023240893
GOLGA4
0.470671062
8.61391E-06
0.000967928
SBNO1
0.467053151
3.3112E-06
0.000483589
HIC2
0.465264904
0.001552439
0.03306235
ARHGEF6
0.46436213
4.13069E-05
0.002890941
LHFPL2
0.464235212
1.33655E-05
0.001300404
AMDHD1
0.461513434
0.000339667
0.012621599
GPSM2
0.461343302
3.30934E-07
7.26297E-05
LIPT2
0.457860911
0.001350959
0.030052382
BOD1
0.457396612
0.000194451
0.008782201
CREBL2
0.456851397
1.66985E-08
5.45459E-06
ZSWIM4
0.454725159
0.000208264
0.009113014
VCAM1
0.452412037
0.000542536
0.016972088
ZNF441
0.452204029
0.000996952
0.024916693
PAX2
0.451189863
0.002760969
0.046981814
ANGPT1
0.450124438
9.37121E-05
0.005350735
SPRED1
0.449934783
0.000242903
0.010005331
PCSK6
0.44752782
6.47817E-05
0.003973466
KIAA1147
0.447169844
5.4371E-06
0.000701239
SLC45A4
0.443566994
0.000223012
0.009579306
DHFRL1
0.442526775
1.29954E-05
0.001288913
FRY
0.441461555
0.001999336
0.03862816
MED21
0.441074062
0.000160305
0.007530589
PLK4
0.438164834
2.407E-05
0.002012427
AIF1L
0.437554259
0.000448505
0.01489291
BMP2K
0.43650997
0.000885198
0.022855684
TMEM65
0.436500989
5.56813E-05
0.003507173
ING2
0.435537424
2.214E-07
5.25109E-05
WSB1
0.434970323
1.41851E-06
0.000262162
FAM19A4
0.433491627
0.00243137
0.04378337
RMI2
0.433230738
1.84801E-05
0.00161225
TOMM20
0.432611531
0.0001255
0.006462374
GPR137B
0.432140946
0.000110674
0.005910731
YRDC
0.431873593
4.42872E-05
0.002994804
NRAS
0.43159367
1.00964E-05
0.001066274
STIM2
0.428215051
0.000213364
0.009267948
G3BP2
0.427849428
8.62523E-11
6.37631E-08
PPP1CC
0.427838671
1.57073E-05
0.001451481
TESK2
0.426926903
0.000246783
0.010105874
PLEKHA5
0.426508645
1.64784E-05
0.001483691
CDK8
0.424442513
3.88579E-05
0.002808317
NTAN1
0.42443504
7.20739E-06
0.000857924
EEA1
0.423991582
6.35793E-05
0.003934072
ERCC5
0.421813797
0.001577531
0.033471297
KATNBL1
0.420601594
3.70958E-05
0.00271379
CIDEB
0.419674529
0.000994688
0.024904443
PTPN3
0.419638217
3.58458E-05
0.002636071
ZNF143
0.418412231
0.000119697
0.006296857
H1F0
0.417627495
0.000163209
0.007641445
FAAP24
0.416550212
0.000201321
0.008934482
GJA1
0.416324894
0.001150017
0.027106682
GLA
0.414672661
9.34974E-05
0.005350735
POLQ
0.413759191
6.75548E-05
0.004107683
GBA
0.412475082
0.000445065
0.014865951
ZDHHC17
0.411924596
1.67464E-05
0.001488732
STX12
0.411732272
4.00986E-06
0.000568915
AKAP7
0.411656295
0.000270877
0.010745219
PVRL3
0.411093224
0.000217761
0.009411295
PREPL
0.410782167
0.000353906
0.012844877
SP4
0.408536925
0.001347899
0.03005172
TDG
0.407263585
3.03286E-05
0.002353564
PLAGL1
0.406657762
1.34244E-05
0.001300404
LAMTOR3
0.406238639
7.89489E-06
0.000901558
DIXDC1
0.405252406
3.39652E-05
0.002553861
PRRC2C
0.404961973
0.000204455
0.008980917
GABPA
0.402784031
2.0123E-05
0.001734038
HMGN5
0.402665522
0.001806644
0.036830372
BTRC
0.402648359
1.31222E-05
0.001288913
HSPD1
0.401802319
1.79438E-06
0.000315048
MED4
0.401161503
1.17082E-05
0.001190671
MAMSTR
0.40080178
0.001454078
0.031519771
SKIL
0.400726805
0.000240187
0.009922569
ANKRD44
0.399826305
0.000155628
0.007486149
CASD1
0.3995631
0.00010217
0.005605781
DET1
0.399308587
0.000125604
0.006462374
SC5D
0.399183706
0.001310365
0.029440137
MAGI2
0.39878402
0.000105947
0.005749612
C1D
0.398515503
0.0004467
0.014868125
ARL6IP5
0.398050569
0.001146779
0.027106682
ARFGEF2
0.39554849
7.6691E-05
0.004545156
SMARCD2
0.395028724
0.000138731
0.006885546
ZSCAN21
0.393515948
0.000306085
0.011651119
ELMOD2
0.39303963
5.44949E-06
0.000701239
EYA3
0.392313927
0.000334547
0.01249748
GORAB
0.392205154
0.00091105
0.023308951
SRGAP2B
0.389257319
0.000667814
0.01933575
FAM133B
0.388690627
0.002003068
0.03864711
SKIDA1
0.38838865
0.001977298
0.038360674
FOXN3
0.387657969
0.000229627
0.009744224
SRGAP2
0.38735527
0.000289103
0.011311264
ZNF625
0.386613139
0.002685761
0.046341781
ENAH
0.386340533
0.000509964
0.016428787
RCOR1
0.386281734
2.51755E-05
0.002072238
C2orf69
0.384767589
0.001204822
0.027788072
NEK7
0.383722681
0.002190509
0.040952756
RAD50
0.38365852
0.000213784
0.009267948
RALGAPA2
0.381402334
0.001196083
0.027631882
COL4A3BP
0.379787699
0.000535738
0.016964399
SYPL1
0.379686594
2.63857E-05
0.002105756
MGME1
0.378864919
0.000440507
0.014773295
STMN1
0.377781548
0.000224701
0.00959315
RRAGC
0.377428393
0.001127614
0.026941873
PLXDC2
0.376303579
0.001529363
0.032896533
RAB7A
0.37586694
0.000758203
0.020880059
ISOC1
0.375663425
0.001689069
0.035199802
HMGB2
0.375259487
0.000706954
0.020100954
MOB4
0.375251374
0.002444575
0.043852496
EPB41L4B
0.375220821
0.000343981
0.012648053
DISP1
0.373164532
0.001239061
0.02839127
ZNF641
0.372862881
0.000859583
0.022567673
SCML2
0.371806486
0.002681092
0.046341781
ANKRA2
0.371257521
0.000416216
0.014414836
ATG2B
0.369074255
0.001987288
0.038501309
TIMM22
0.36869627
8.11502E-05
0.004769187
MBTPS1
0.368666762
1.45331E-05
0.001388648
ATF1
0.367788456
0.000367836
0.013146615
APBB2
0.367636769
0.000302826
0.011558414
ESYT2
0.367609065
1.12842E-06
0.000217121
COX10
0.366474873
0.000231198
0.009781362
DDX3X
0.365974588
1.82506E-05
0.001602172
ALDH3A2
0.365755806
0.002577868
0.045148052
CEP135
0.364292587
0.001016934
0.025325976
ZNF738
0.36326512
0.001139002
0.027026409
ALG9
0.363252169
3.49722E-05
0.002612872
KLF3
0.362116765
0.000325375
0.012252583
C1orf21
0.361725135
0.001190521
0.027611899
ALG14
0.361172886
0.001900089
0.037484069
UEVLD
0.360988169
0.001855956
0.037030036
PPP3CB
0.36079551
1.54514E-05
0.00143729
DDX10
0.36025669
0.002284524
0.041781801
CDC25A
0.358062394
0.001307101
0.029422339
CTNS
0.357501567
0.000535243
0.016964399
JAZF1
0.357354903
0.002158071
0.04061926
MBNL3
0.356986384
0.000693578
0.019841126
PNRC2
0.356804624
0.001116376
0.026879785
RTN4
0.35633992
2.17691E-05
0.001864445
CTBP2
0.35396556
0.000147968
0.007209639
PPFIBP1
0.353462181
0.001358213
0.030052382
SEPT11
0.351952745
0.002657573
0.046141256
PIK3C2A
0.351488017
0.000717442
0.020235321
THAP1
0.351469324
0.001104581
0.026749899
HMGCR
0.351171023
0.002974969
0.049627577
RNF6
0.349822363
0.000651893
0.019128984
TRMT10A
0.349734868
0.000920259
0.023501741
SPOPL
0.34960625
0.000841028
0.022246853
TADA2B
0.347219856
0.000558111
0.017229075
DCP1A
0.34689833
0.000380416
0.013436491
PDS5B
0.346096563
0.002179739
0.040876648
SLC44A2
0.345427114
0.000646636
0.019121368
IRS1
0.343972684
0.001256726
0.028563054
PUM2
0.342604439
0.001188783
0.027611899
THOC2
0.341528224
0.000708638
0.020108128
RIF1
0.339507294
0.000578274
0.017773395
PRPF38A
0.339224598
5.26395E-06
0.000691004
MTRF1L
0.338211507
0.002356839
0.042770232
VPS54
0.336510146
0.000123389
0.006408328
MAPK6
0.336395793
0.000670405
0.01933575
SSH2
0.336009178
0.002107529
0.039969929
PHACTR2
0.335704523
0.002703122
0.046394763
COX17
0.335499503
0.000675884
0.0194197
ZNHIT6
0.335282833
0.000955332
0.024045625
NUP50
0.334955768
0.001191287
0.027611899
TRPM7
0.334780224
0.000541083
0.016964399
STAG2
0.334718384
1.30478E-05
0.001288913
RPE
0.334605394
0.001638517
0.034453012
MAGI1
0.334246557
0.00188752
0.03738556
BPTF
0.333898755
0.001324294
0.029666726
CRY1
0.333596293
0.001816707
0.036920417
C9orf40
0.332332754
0.000234069
0.00981857
HMGN2
0.3321557
0.002199918
0.040952756
RCC2
0.331879266
3.57643E-05
0.002636071
GOPC
0.329605391
0.001671537
0.034990186
TRDMT1
0.328861946
0.002196466
0.040952756
RYBP
0.328018844
0.001450447
0.031519771
ZNF12
0.327007104
7.65808E-05
0.004545156
ZNF627
0.326584405
0.001045671
0.025914426
H2AFY2
0.326467185
0.00283827
0.04803174
GOLT1B
0.325426114
0.000431697
0.014681872
SMAP1
0.325255591
0.000423657
0.014478539
AMD1
0.32473083
0.001553549
0.03306235
THUMPD1
0.324670826
0.001141012
0.027026409
HSPA4L
0.324414833
0.002537165
0.044882888
CHEK1
0.324001614
0.00011252
0.005986599
CCDC93
0.323912839
0.000420766
0.014414836
TARS
0.322949467
0.001101285
0.026716143
RAD21
0.321665368
0.00109034
0.026496403
TSC1
0.321648287
0.000720341
0.020262828
SFMBT1
0.320524563
0.000445576
0.014865951
SEC62
0.319961853
0.000337734
0.01258306
RP9
0.319282209
0.001563566
0.033225177
PEG10
0.319210855
0.000710211
0.020110932
EXOC6
0.316621398
0.000200111
0.008934482
KIAA1033
0.315453195
0.000752132
0.020796165
ARMC8
0.314234535
0.000253325
0.010313635
PTPN12
0.314170623
0.000580149
0.017792076
TVP23B
0.312708104
0.000628744
0.018750175
PTPN2
0.312209824
0.000123641
0.006408328
NUMB
0.311911357
0.002282628
0.041781801
CDH2
0.31185075
0.002703485
0.046394763
FAM122A
0.311641026
0.002461317
0.044040328
POLR3F
0.311273787
0.002011294
0.038702111
DDX17
0.310614711
0.001174926
0.027467601
FBXL7
0.309267515
0.000211465
0.009224323
DSCR3
0.308384026
0.000237409
0.009861816
STX6
0.308360284
0.000499729
0.0162106
FNTA
0.307814088
0.000518436
0.016658293
SLC31A1
0.307424643
2.58181E-05
0.002072238
LZIC
0.306907626
0.002377631
0.043036349
INSR
0.306531283
0.001058994
0.026141706
SON
0.306284559
0.000871091
0.022658038
FAR1
0.30248949
0.001837074
0.037017786
TMEM168
0.302476342
0.001783243
0.036512285
HMGN1
0.302185044
2.57813E-05
0.002072238
SLC9A6
0.301992132
0.001083134
0.026412674
LARP7
0.301509875
0.00027028
0.010745219
ZHX1
0.300855887
0.000258485
0.010403085
TLK1
0.300827492
0.001262319
0.028643837
KLHL42
0.299468829
0.000158843
0.007521722
NOP56
0.298995746
0.000321622
0.012176558
EIF3A
0.298724279
0.000106429
0.005749612
PTK2
0.298496449
0.000100535
0.005537698
FEZ2
0.297984984
0.001840929
0.037017786
PATL1
0.297161206
0.00075768
0.020880059
OGT
0.296896763
0.000333009
0.012473194
UBE2D3
0.296781724
0.000495105
0.016097789
PANK3
0.295944426
0.000792952
0.021377733
PRKAR2B
0.295931498
0.000847233
0.022368858
TBC1D15
0.295395134
0.000425652
0.014511431
DMTF1
0.2938517
0.000598683
0.018084104
STK4
0.293842951
0.002057002
0.039363289
MRPL48
0.293591034
0.002953778
0.049406943
USP32
0.292949692
0.002448418
0.043865401
CD59
0.291844338
0.001964856
0.038199261
MTAP
0.290632559
0.000236342
0.009861816
DCAF10
0.287975987
0.002211534
0.041005242
GSE1
0.287864863
0.000589496
0.018000141
PTPN1
0.287810036
9.92466E-06
0.001056074
NUS1
0.287306166
0.00107363
0.026272143
RNF139
0.286322489
0.000264917
0.010631488
AKIRIN1
0.285247035
0.001150191
0.027106682
PPIA
0.284955678
0.000435424
0.014737258
RPIA
0.283708539
0.002574449
0.045144454
IPO7
0.283270632
0.002348966
0.042737787
CD3EAP
0.282782185
0.002756528
0.046981814
PPP6R3
0.282021692
9.03905E-05
0.005224797
POLR3A
0.282012288
0.001341146
0.029996395
RWDD4
0.281858937
0.002605199
0.045456685
CDCA4
0.281398791
0.00247392
0.044097317
CHUK
0.280732377
9.90725E-05
0.00552211
ALG5
0.28067173
0.001231594
0.028312553
SDCBP
0.27988087
0.000958675
0.024045625
MAPK1IP1L
0.278660767
0.000142858
0.007065431
LAPTM4A
0.278390698
0.000341806
0.012634244
SMARCD1
0.278090473
0.000302219
0.011558414
MORF4L1
0.277700081
4.15755E-05
0.002890941
NET1
0.277688274
0.002036267
0.039072959
SAP130
0.276860625
6.0866E-06
0.00075657
SPPL2A
0.276832305
0.00041561
0.014414836
DAZAP2
0.275639531
0.000738692
0.020586655
BTF3L4
0.275348683
0.002299223
0.04199596
KIAA0513
0.275061531
0.00285932
0.048329736
RSRC1
0.274491319
0.0008844
0.022855684
ADIPOR1
0.274198767
0.000655865
0.019192241
RUFY1
0.274160054
0.002336337
0.042618437
RABL3
0.273643297
0.001852892
0.037030036
DYRK1A
0.273250137
0.000663783
0.019303292
DNAJC9
0.272546626
4.31139E-05
0.002954038
NCKAP1
0.271690051
0.000868033
0.022658038
VMP1
0.271170382
0.002504635
0.044434417
LINC01578
0.270556436
0.002688919
0.046341781
PHAX
0.270146015
0.001454137
0.031519771
TNPO3
0.269143137
0.000748183
0.020727779
ITGB1
0.269069865
0.002205309
0.040973232
FAM103A1
0.267733405
0.001435433
0.031307595
AHI1
0.267232326
0.002439216
0.043852496
PPP4R3A
0.267143052
0.000196962
0.008867068
ARF6
0.266389047
0.00201143
0.038702111
ABHD10
0.264978388
0.002077722
0.039650849
RABGAP1
0.264895918
0.001777243
0.036512285
KPNA1
0.26458193
0.000160234
0.007530589
NUP160
0.264302759
0.002801305
0.047520689
TOPBP1
0.264281887
0.001618248
0.034180318
USP46
0.263980039
0.002882272
0.048536712
TTL
0.263551615
0.002783526
0.047276185
WAC
0.263447042
0.002882589
0.048536712
RSL24D1
0.262881874
0.002585017
0.045170447
SEPHS1
0.258387825
0.000440696
0.014773295
TXLNG
0.256796441
0.002263242
0.041656772
GPBP1
0.256384375
0.001108907
0.026808457
SPG20
0.256091557
0.000267948
0.010692056
CASK
0.255870751
0.00193501
0.037906768
PFN1
0.25529201
0.000126895
0.00649253
CFL2
0.254064536
0.000933382
0.023707554
SRSF11
0.253974623
0.0021243
0.04021282
RPL15
0.253039591
0.001173256
0.027467601
SMUG1
0.252699312
0.001509533
0.032519795
LARS
0.251807986
0.001072252
0.026272143
SMC1A
0.251579896
0.002201291
0.040952756
TCERG1
0.251313253
0.001959763
0.038178679
NPTN
0.250618556
0.001714129
0.035506783
TOMM6
0.249729858
0.000554329
0.017187875
DHX15
0.243819556
0.001821514
0.036920417
SEL1L
0.241778894
0.002885388
0.048536712
HOXA10
0.240812123
0.001363604
0.030115065
SMC3
0.238169996
0.002549814
0.044949964
ARCN1
0.234152434
0.001220339
0.028099795
PKM
0.233646356
0.000100368
0.005537698
HIF1 AN
0.232009054
0.002274102
0.041754294
DHX9
0.231546852
0.000271576
0.010745219
SP3
0.230691455
0.001930639
0.037906768
IREB2
0.230625736
0.001874228
0.037216549
RBBP6
0.230551606
0.000955763
0.024045625
POLR2K
0.230372864
0.001869455
0.037216549
ZNF655
0.229860798
0.001491069
0.03222085
SEC31A
0.229382654
0.00140326
0.030749133
CUTA
0.229272721
0.000810129
0.021715774
SERBP1
0.226265573
0.000805097
0.021634524
SET
0.224759899
0.002551022
0.044949964
ATXN7L3B
0.224274791
0.002363149
0.042829413
TACC1
0.223618705
0.001661834
0.034891069
SARS
0.219920223
0.001824204
0.036920417
SRSF4
0.219554521
0.001872582
0.037216549
CWC15
0.219531355
0.001252857
0.028563054
ZDHHC7
0.217271571
0.001122824
0.026941873
PARD3
0.21682903
0.000234088
0.00981857
CNOT2
0.206050296
0.002876694
0.048536712
CAPZA2
0.201801085
0.002679607
0.046341781
TSTD2
0.201039339
0.001358626
0.030052382
DLD
-0.18955922
0.001312084
0.029440137
EIF4H
-0.197944909
0.0012384
0.02839127
CMTR1
-0.231337833
0.00221287
0.041005242
ATOX1
-0.232397299
0.002521409
0.044660412
C6orf120
-0.234397669
0.001088531
0.026496403
VIM
-0.237518011
0.000159045
0.007521722
RSU1
-0.237935816
0.000324253
0.012243158
CSNK1A1
-0.244201077
0.001678568
0.035032945
VOPP1
-0.251570066
0.0016966
0.035304361
TMED4
-0.25195419
0.002108623
0.039969929
EIF2B4
-0.255725896
0.001824066
0.036920417
CD81
-0.257026802
0.00238854
0.043178157
ACTR1A
-0.258409012
0.001127853
0.026941873
DTD1
-0.273831895
0.0007116
0.020110932
GALNT13
-0.27530258
0.001942094
0.037931801
NAPG
-0.275519677
0.001346003
0.03005172
YBX3
-0.276012382
0.002093287
0.039829755
ITPK1
-0.276848888
0.001538921
0.032950733
CMSS1
-0.278271818
0.002812339
0.04765031
BLVRA
-0.279590992
0.000633113
0.018840475
PROSER1
-0.281296004
0.001068532
0.026262955
HYOU1
-0.281714706
9.34739E-06
0.001017778
DCTN2
-0.284412983
0.001273454
0.028803446
NLN
-0.288287981
0.001411569
0.030883023
PLXNB2
-0.288305458
0.001137613
0.027026409
IDE
-0.288746288
0.000593211
0.018035147
LIMA1
-0.294062993
0.001245209
0.028439355
ETV6
-0.295473593
0.000418155
0.014414836
RUVBL2
-0.295504777
0.002965763
0.049532826
TCF7L2
-0.295882155
0.00055625
0.017209456
C18orf25
-0.297227842
0.00192101
0.037827605
SLC35B4
-0.29755565
0.002585579
0.045170447
ASPH
-0.299610908
0.000649186
0.019121485
PDZRN3
-0.301259536
0.000484477
0.015862379
G6PD
-0.30152022
0.002505486
0.044434417
HDAC5
-0.313999158
0.000100146
0.005537698
ZXDB
-0.314671352
0.00194439
0.037931801
FBXO42
-0.315501204
0.000156282
0.007491945
CDH12
-0.316903871
0.000201729
0.008934482
POLDIP2
-0.317409657
0.000590931
0.018004799
DECR1
-0.318453237
0.001014509
0.025310471
SRM
-0.31878575
0.00012756
0.00649253
CASP7
-0.320077144
0.000584768
0.01789468
MANEAL
-0.322196333
0.000349847
0.01281619
TRAPPC4
-0.322893354
0.001505325
0.032478951
COMMD7
-0.324364295
0.001538061
0.032950733
GINM1
-0.325094944
0.000825677
0.021933556
GTF3C2
-0.325570881
0.001675622
0.035023482
BCL2L1
-0.326087164
0.002762849
0.046981814
ABR
-0.326576523
0.000784719
0.021316165
ADCK4
-0.326780855
0.002709485
0.046394763
UBE2Q2
-0.329210343
0.002903786
0.048770984
PCTP
-0.333633317
0.000638535
0.018921653
ETNK2
-0.335000092
0.002544359
0.044949964
ZWINT
-0.335763678
0.002143696
0.040426363
TMED2
-0.336707812
9.47973E-06
0.001024249
AXIN2
-0.338658517
0.000956931
0.024045625
TTC12
-0.338889604
0.002954708
0.049406943
SLC25A3
-0.339353223
0.000110039
0.005910731
FCHO2
-0.339604515
0.000128677
0.006524883
ZBTB8A
-0.340052411
0.00052061
0.016658293
TIRAP
-0.341254482
0.002231041
0.041224498
LYRM7
-0.342076969
0.002076333
0.039650849
ABHD4
-0.342996216
7.32855E-05
0.004380293
AGPAT2
-0.346788136
0.00216023
0.04061926
LRPAP1
-0.347998354
5.18508E-06
0.000691004
UNKL
-0.349246435
1.96013E-06
0.000331711
IQCH
-0.353745978
0.002692886
0.046353278
TMEM245
-0.35790812
0.000138494
0.006885546
ATP13A2
-0.359071693
0.000778206
0.021265931
SOD2
-0.359358127
3.14915E-05
0.002430384
KIF1C
-0.359629896
0.000350379
0.01281619
ZNF367
-0.359808737
0.000190532
0.008660826
FAM46C
-0.36095502
0.001628866
0.034352934
PAQR5
-0.361298866
0.000705149
0.020090305
CHPF
-0.361398189
0.000536652
0.016964399
FLII
-0.361814698
1.46516E-06
0.000263841
GANAB
-0.361844254
3.06361E-06
0.000452963
PRKCSH
-0.362106771
2.76988E-05
0.00218133
RALGDS
-0.362384624
0.000864663
0.022658038
ZNFX1
-0.363369962
0.00026758
0.010692056
EMC2
-0.364571461
4.43485E-05
0.002994804
C14orf159
-0.365341675
0.000255148
0.010324939
KIAA1804
-0.365847835
0.000367516
0.013146615
DYRK2
-0.366212609
0.000684389
0.01961821
MOSPD1
-0.36638983
0.000169006
0.007860451
STK36
-0.366523579
0.000204606
0.008980917
NSUN4
-0.368695918
9.64572E-05
0.005445493
C4orf3
-0.36875413
2.56589E-05
0.002072238
UBL7
-0.369183736
0.000746402
0.020727779
HINT3
-0.369265759
5.50413E-05
0.003498239
SEPW1
-0.37098234
0.002467269
0.044071809
ZNF436
-0.372325474
0.00187593
0.037216549
NTM
-0.372478379
0.001934837
0.037906768
IKBKE
-0.372689604
0.001716439
0.035506783
UBA7
-0.37350552
0.001022591
0.0254218
CIPC
-0.373567979
0.000596132
0.018084104
MPI
-0.373727063
0.000154652
0.007464731
MOCS1
-0.374219449
0.000467352
0.015409452
LIX1L
-0.374295856
0.00219106
0.040952756
DPCD
-0.376065952
0.000404866
0.01414613
EIF3I
-0.376198078
2.75728E-05
0.00218133
TBL1X
-0.376637546
0.000294434
0.011328988
SIMC1
-0.37724029
0.000892207
0.022994381
RALY
-0.377792645
0.000394248
0.013860632
C1orf198
-0.377807865
4.13964E-05
0.002890941
FGF13
-0.378542053
4.23563E-05
0.002916359
IL17RC
-0.379254808
4.65965E-05
0.003101868
TERF2IP
-0.379570535
0.000553878
0.017187875
BRE
-0.379775815
5.35842E-05
0.003421109
ESYT1
-0.380574637
0.000157055
0.007503361
BRINP2
-0.380581557
0.000351919
0.012839087
PMP22
-0.38067865
0.000539599
0.016964399
FLYWCH2
-0.380711517
0.001852947
0.037030036
VPS9D1-AS1
-0.381135646
0.00093059
0.023705862
PFKP
-0.382127849
0.002493961
0.044398194
TBC1D19
-0.382239745
0.000788663
0.021318877
ENGASE
-0.383298422
0.001439565
0.031349036
CRELD2
-0.384977508
0.001892434
0.03738556
GLB1L2
-0.385156758
0.000738157
0.020586655
IGSF8
-0.387147313
0.000852839
0.022474638
SS18
-0.387235712
9.15583E-06
0.00101262
SS18L2
-0.389148718
0.000197627
0.008868595
ARSB
-0.389243781
0.00192289
0.037827605
BCL2L2
-0.390273391
0.000134406
0.00674239
DNAJB2
-0.391799529
0.000353522
0.012844877
ANGEL2
-0.393081934
0.000145532
0.007147339
STAT5A
-0.393197431
0.002642584
0.045994708
EML1
-0.39346381
0.000634771
0.018849892
AGAP2-AS1
-0.39360994
0.001707615
0.035480996
CASP9
-0.393612609
0.001379371
0.030367788
CKAP4
-0.394619317
0.000473083
0.015525523
SDF2L1
-0.39524631
0.000546006
0.017042663
CLDND1
-0.397217482
0.000341719
0.012634244
CD151
-0.398468043
0.000238015
0.009861816
ETFB
-0.398720489
0.000219381
0.009452208
PPP1R26
-0.39995587
0.000252011
0.010289979
TMEM167A
-0.400093473
4.9037E-06
0.000662283
SLC25A23
-0.400927625
0.001966258
0.038199261
C1QTNF1
-0.401168716
0.002052709
0.039334725
TLE3
-0.401398313
0.002135091
0.040362706
STIM1
-0.401941438
0.000669589
0.01933575
RNF43
-0.404960099
0.001400411
0.030734634
ZNF385A
-0.405631311
0.000823265
0.021933556
APLP1
-0.408276246
0.000665839
0.019323101
ARRB2
-0.408589642
0.001163031
0.027363368
PPP1R18
-0.409142825
7.71926E-06
0.000888728
MMP24-AS1
-0.410198376
5.244E-05
0.003363343
ZNF652
-0.411188273
0.000789251
0.021318877
NT5DC1
-0.411634516
2.36972E-06
0.00037082
SPATA20
-0.414131633
4.85508E-05
0.003186654
RFPL1S
-0.415076106
0.000181169
0.008356893
LGMN
-0.415303003
2.5771E-05
0.002072238
NT5C3A
-0.415499535
0.001114395
0.026879785
INPP5J
-0.415818804
0.001265816
0.028676861
OGFRL1
-0.416085215
0.001782811
0.036512285
CTNNBIP1
-0.417560868
0.000144264
0.007109914
NEFL
-0.417743173
8.94267E-05
0.005190442
FAM43A
-0.418145855
0.001779811
0.036512285
THSD4
-0.421651594
0.000568783
0.017520013
TMSB15B
-0.422603964
0.002095557
0.039829755
CNKSR2
-0.423317565
0.001793541
0.036616382
GPC4
-0.425104615
0.000437714
0.014743703
STMN3
-0.425165643
0.000202276
0.008934482
MARCH2
-0.425459881
0.002265825
0.041656772
SLC36A1
-0.426204089
0.001083085
0.026412674
C10orf82
-0.426244241
0.000174103
0.00807079
IL13RA1
-0.426594979
0.000598599
0.018084104
CCDC113
-0.426878644
0.001063155
0.02619837
NEFM
-0.426937624
0.000786115
0.021316165
DOHH
-0.427682394
0.002168339
0.040717227
MR1
-0.427919433
9.88282E-05
0.00552211
NUMBL
-0.42835969
0.000355213
0.012859068
SYNJ2
-0.429143866
0.000397474
0.013922498
TTC7A
-0.429594406
1.4714E-05
0.001396434
MFSD12
-0.429838904
0.002236442
0.041224498
ULBP3
-0.430078326
0.001185826
0.027611899
SYT5
-0.430461379
0.002235107
0.041224498
B9D1
-0.432810433
0.00135322
0.030052382
USO1
-0.432872777
0.000814007
0.02177818
TP53I13
-0.43863385
0.000488016
0.015941105
P2RX4
-0.439362102
0.000191147
0.008660826
LONRF1
-0.440986752
0.00094513
0.023962622
C9orf3
-0.441101619
5.23478E-05
0.003363343
MYH14
-0.441160929
3.9524E-05
0.002832422
NPY6R
-0.442195208
0.000343149
0.012648053
APBB3
-0.442865089
0.002713247
0.046394763
LHX6
-0.442938229
0.001748151
0.036056568
TBCEL
-0.443275671
3.21496E-05
0.002467617
AHRR
-0.444146743
0.002570672
0.045134575
TAP1
-0.44446719
0.000676081
0.0194197
SIRT2
-0.445068737
3.89371E-05
0.002808317
XYLT2
-0.445515811
0.000255038
0.010324939
DPF3
-0.445592814
0.002714289
0.046394763
PCBD1
-0.445972248
0.000737199
0.020586655
FAM129B
-0.446463298
0.001139095
0.027026409
ANGPTL2
-0.446780249
3.24733E-05
0.002478914
C4orf19
-0.44738555
0.001792654
0.036616382
KRBOX4
-0.447754187
0.000658475
0.019211693
MYLK
-0.448741576
0.002559109
0.044987799
RILPL1
-0.448791742
5.54767E-05
0.003507173
DAAM2
-0.448823242
0.000759626
0.020880059
EFNA1
-0.449256838
2.78609E-05
0.00218133
SHISA4
-0.450339606
0.001459243
0.031581714
DNAL1
-0.450889309
4.96028E-05
0.003225562
IL1RAP
-0.451197949
0.0012564
0.028563054
AAED1
-0.452243944
0.000329884
0.012389189
HERC6
-0.452249513
0.000132256
0.006658328
PARVB
-0.453214539
0.001175283
0.027467601
LDLRAD3
-0.453764279
2.77678E-06
0.000419383
SMAD6
-0.453943356
0.001636613
0.034453012
POU3F2
-0.455378468
0.002748036
0.04690026
SAMHD1
-0.455829418
0.000104038
0.005686039
L3MBTL3
-0.455968479
0.002715114
0.046394763
GLIPR1
-0.456582849
0.000736233
0.020586655
CSRNP2
-0.456747361
4.60803E-05
0.003096864
FAHD2B
-0.457057508
0.000884093
0.022855684
SLC44A5
-0.458087791
0.001069515
0.026262955
KLF10
-0.458898715
0.001542554
0.032978264
IRX5
-0.459053565
0.00194262
0.037931801
CLPP
-0.459610241
0.00018959
0.008646033
INAFM1
-0.460039056
0.000700343
0.019993948
ADSSL1
-0.460356856
0.000824854
0.021933556
TCTA
-0.460511768
1.18385E-05
0.001190671
WNT11
-0.461732135
1.13095E-07
2.88825E-05
DOCK5
-0.463175019
0.002553757
0.044949964
FOSL2
-0.464421163
0.000148367
0.007209639
KNDC1
-0.465194962
0.000201941
0.008934482
PCDHGC3
-0.466497551
0.000224596
0.00959315
HDAC9
-0.469822757
2.33889E-07
5.38559E-05
TRAM2-AS1
-0.470487559
0.000282671
0.011121547
TTC19
-0.470897323
7.4093E-06
0.000874546
SMIM14
-0.471037679
4.02493E-05
0.002855259
NUDT11
-0.471908918
2.69614E-06
0.00041163
MXD4
-0.472438498
0.000361208
0.01297738
TGM2
-0.472892189
0.001389601
0.030545121
ADAM15
-0.473350894
0.000283745
0.011132614
KCND1
-0.473951944
0.000854641
0.02247993
DACT1
-0.474412177
0.00012272
0.006407899
QSOX1
-0.475206567
7.63237E-06
0.000888728
RABGAP1L
-0.476639265
0.000110265
0.005910731
ABHD14B
-0.476891423
2.25443E-05
0.001907572
ESRRA
-0.477343823
0.002469352
0.044071809
TPRKB
-0.478062461
8.74214E-05
0.00509511
GYLTL1B
-0.481037402
0.000528997
0.016848739
MBNL2
-0.481543963
0.000119296
0.006296857
TNFRSF19
-0.482114792
0.000614527
0.018411192
CERS4
-0.483640624
0.002654823
0.046141256
RAB23
-0.485770897
0.000245808
0.010095359
MB
-0.488054518
0.000649363
0.019121485
DENND6B
-0.489852192
0.001047968
0.02591506
CIART
-0.490854722
0.002910108
0.048777297
GALK1
-0.491300999
0.000460737
0.015227088
TTC39A
-0.492479143
0.001998933
0.03862816
MGLL
-0.492959515
0.001822311
0.036920417
BLOC1S3
-0.493563393
0.000659265
0.019211693
EFNA3
-0.494113251
0.001302777
0.029419295
PSMG3-AS1
-0.496013582
0.000147745
0.007209639
PNPO
-0.496508691
7.09397E-07
0.000144408
RFWD2
-0.496614603
1.02787E-07
2.6736E-05
CNTNAP1
-0.496626485
0.000293817
0.011328988
TXNDC5
-0.497248349
0.000292784
0.011328988
SECISBP2L
-0.499016584
1.18677E-05
0.001190671
PRKAG2
-0.500425098
0.000506888
0.016367228
LMO2
-0.501075181
0.000540769
0.016964399
PER2
-0.501854023
0.00084011
0.022246853
ARHGEF10L
-0.501966897
0.000277721
0.010957493
CTXN1
-0.504310051
0.002684638
0.046341781
SSC4D
-0.504705508
0.000361253
0.01297738
CTDSPL
-0.505037045
2.98624E-06
0.00044622
FLT3LG
-0.505417018
0.001729865
0.035731892
ASB13
-0.505460723
1.43828E-06
0.000262365
UNC93B1
-0.506966898
0.00077561
0.021236287
HSPB8
-0.50782772
1.94349E-06
0.000331711
CPLX1
-0.507831696
0.000931627
0.023705862
PXYLP1
-0.510843522
0.000957283
0.024045625
MME
-0.511434533
1.98407E-06
0.000331764
CLEC11A
-0.511806905
0.001371536
0.0302427
TMEM221
-0.512165246
0.002281395
0.041781801
PINK1-AS
-0.513259404
0.000418885
0.014414836
CTSS
-0.514547634
0.000237733
0.009861816
GABBR2
-0.515138195
0.001117599
0.026879785
GRIPAP1
-0.515226466
9.31359E-09
3.4426E-06
PHEX
-0.515275715
0.002610602
0.045494441
TBX2
-0.517520977
0.001183925
0.027611899
FLOT2
-0.519774259
6.19161E-06
0.000762872
MAPK8IP2
-0.520932468
0.000652341
0.019128984
PER1
-0.521149449
0.000952188
0.024045625
CRY2
-0.521221596
9.67601E-05
0.005445493
ST7-AS1
-0.521456062
0.002416455
0.04362664
ISG20
-0.523027157
0.001244966
0.028439355
SNTA1
-0.524779364
5.16123E-05
0.003340765
EIF4E3
-0.525059766
4.15459E-06
0.000583553
LOC101926913
-0.525196407
0.000520646
0.016658293
AFP
-0.525295041
0.002421064
0.04365375
POU6F1
-0.527057757
7.46254E-09
2.99482E-06
CDH8
-0.528622693
0.001855984
0.037030036
TUBB3
-0.528657927
0.000805557
0.021634524
TMEM56
-0.528868206
8.26787E-06
0.000936536
TSPAN33
-0.530707302
0.001550422
0.03306235
RANBP10
-0.530816555
2.76342E-08
8.43804E-06
IGFBP2
-0.531165496
3.40006E-05
0.002553861
TAPBPL
-0.53124793
0.000721302
0.020262828
ADGRG1
-0.532216366
0.001755702
0.036159217
MIEF1
-0.533321369
1.09594E-08
3.75451E-06
FAM213B
-0.534547823
0.000292254
0.011328988
SHANK1
-0.534613458
0.000157626
0.007505154
CCDC96
-0.534646991
0.000780799
0.021295342
MERTK
-0.537425316
3.33961E-06
0.000483589
TBC1D2B
-0.538679627
1.48955E-05
0.001404175
LRFN4
-0.539632993
0.001195081
0.027631882
GRIK2
-0.540576353
6.71169E-06
0.000812693
CXCL16
-0.54132552
4.20633E-05
0.002910448
FAS
-0.541598744
0.000295202
0.011328988
FZD7
-0.542524738
2.55075E-07
5.77867E-05
GNB2
-0.542578021
6.3959E-06
0.00078119
SLC48A1
-0.542982391
6.99806E-06
0.000840126
APC2
-0.543614914
0.000449986
0.014906842
HOXD-AS2
-0.546024791
0.002193845
0.040952756
UNC13A
-0.551100298
1.07003E-05
0.001105119
GPC1
-0.5520851
1.37384E-05
0.001321705
CSF1
-0.552130403
0.002500946
0.044434417
KCNIP3
-0.552860149
0.002443454
0.043852496
SLC2A1
-0.554087991
1.0519E-05
0.001102607
CHST3
-0.554343781
0.002018013
0.038775657
SPARCL1
-0.554480604
0.001890658
0.03738556
DACT3
-0.554858619
0.000106022
0.005749612
CRIP2
-0.555167579
0.002356449
0.042770232
PTPRG
-0.555659485
4.15483E-05
0.002890941
FOXP4
-0.556585285
4.95512E-05
0.003225562
IGFBP3
-0.557963659
0.001046097
0.025914426
KIAA0040
-0.558028607
7.24318E-05
0.004360776
APCDD1
-0.559043297
4.81746E-05
0.003176808
PTX4
-0.560636385
0.002144215
0.040426363
CGREF1
-0.561098532
0.001131474
0.026982488
CCND1
-0.563235341
0.001842192
0.037017786
MYCBP
-0.56355763
0.000761487
0.020890338
TRIM7
-0.564788406
0.001838457
0.037017786
LOXL1-AS1
-0.566284789
0.001832078
0.037017786
GFM1
-0.566680011
7.13442E-08
1.9649E-05
IGF1
-0.567381762
0.001714399
0.035506783
GAP43
-0.569488661
0.00160848
0.034025175
DOCK9-AS2
-0.569547846
0.000870664
0.022658038
MAOB
-0.569577918
0.00047046
0.015475587
CTNNA2
-0.570114945
0.001305527
0.029422339
SLC35F3
-0.570302281
0.000784671
0.021316165
ARID5B
-0.572716739
2.34875E-06
0.00037082
KLK4
-0.575010363
0.001356082
0.030052382
CASC15
-0.575365078
0.001605175
0.034006473
C10orf54
-0.578047152
0.001173755
0.027467601
FIBCD1
-0.584961174
0.000129909
0.006563669
IRF9
-0.586607695
1.81901E-05
0.001602172
KATNB1
-0.587679086
2.34339E-09
1.21908E-06
MESDC2
-0.589824252
4.50571E-08
1.30969E-05
GFRA2
-0.590776308
0.001127405
0.026941873
MAP1A
-0.592651962
0.000255808
0.010324939
SLC2A13
-0.595761746
2.37604E-06
0.00037082
GPC6
-0.598308337
0.000604013
0.018166948
PPM1L
-0.599206249
0.000877182
0.022774298
HLF
-0.6008902
0.000747278
0.020727779
KCNN1
-0.601876415
2.79538E-05
0.00218133
ISM1
-0.602154848
7.80598E-05
0.004606841
MITF
-0.605389764
8.75823E-06
0.000976334
PYGM
-0.606721761
0.000896577
0.023064682
LACC1
-0.610835938
0.000826061
0.021933556
LOC101926911
-0.61343965
0.000127576
0.00649253
SYT14
-0.613459264
7.12015E-05
0.00431076
PPL
-0.614089986
0.000374362
0.013312127
BTG3
-0.614376638
5.70678E-06
0.000722139
ICAM5
-0.619051184
9.69225E-05
0.005445493
POGLUT1
-0.619579346
8.26535E-09
3.13771E-06
MDM2
-0.619919793
2.64074E-06
0.000407603
HAR1A
-0.620325604
0.000435096
0.014737258
SPTLC3
-0.621175966
3.38951E-05
0.002553861
DIRAS1
-0.623610456
0.000623362
0.01862925
LOC101928069
-0.624868806
0.000380729
0.013436491
LRP12
-0.626073294
2.04314E-07
4.94792E-05
NTF4
-0.628437895
0.000489997
0.01596866
RBM20
-0.633123092
0.000417735
0.014414836
SESN3
-0.640332205
9.32273E-05
0.005350735
DBNDD1
-0.64140089
1.06332E-05
0.001105119
CPLX2
-0.641549831
0.000307053
0.01165641
LIN7B
-0.642535312
2.21336E-05
0.001884172
GRIN3A
-0.642763318
9.32718E-06
0.001017778
ADRA2C
-0.651600611
6.44624E-05
0.003971223
PRICKLE1
-0.652119732
4.38332E-06
0.000607863
LOC100129550
-0.653117052
1.94877E-06
0.000331711
DTNA
-0.658747242
1.197E-07
3.00234E-05
FAH
-0.659241708
1.07275E-09
6.27828E-07
IFI44L
-0.66027456
1.32697E-06
0.000248515
ZBTB34
-0.660389866
8.54485E-07
0.000169044
PCDHB17P
-0.66322077
0.000116194
0.006158694
PLEKHA4
-0.667929614
1.62892E-05
0.001476118
JAK3
-0.668934613
3.53464E-05
0.002626851
NDUFB5
-0.671842934
4.33263E-09
1.90176E-06
LIMK1
-0.676718342
3.80553E-12
4.85932E-09
RHOU
-0.680751199
7.69899E-07
0.000154486
C9orf173-AS1
-0.681476563
4.75E-05
0.003147097
SLIT3
-0.684192819
4.54709E-07
9.82592E-05
CALU
-0.689253472
4.5689E-08
1.30969E-05
HOXC8
-0.689591349
0.000148853
0.007209639
CEMIP
-0.692950698
6.74769E-05
0.004107683
CPM
-0.694065784
4.7039E-07
0.000100107
USP2
-0.694756026
9.63431E-05
0.005445493
COL26A1
-0.696940708
7.66294E-06
0.000888728
KREMEN2
-0.700134104
3.89877E-05
0.002808317
PIGZ
-0.701117173
2.57706E-05
0.002072238
FSCN1
-0.704413338
5.7145E-09
2.36076E-06
KIAA1143
-0.706735395
2.0098E-11
2.01641E-08
SLC39A14
-0.710947721
2.69494E-11
2.52354E-08
CHRD
-0.714928435
5.66147E-05
0.003534264
IL15RA
-0.716248903
3.99644E-05
0.002849439
GEMIN7
-0.721382804
4.57366E-09
1.94672E-06
PPP1R1A
-0.736878442
4.36619E-05
0.002977064
PTCHD4
-0.747878645
5.49169E-06
0.000701239
EFHD2
-0.752470311
5.79345E-11
4.78675E-08
SYNC
-0.754622598
2.388E-05
0.002008492
ISOC2
-0.758205452
9.80078E-09
3.52979E-06
L3MBTL4
-0.777717184
1.88771E-05
0.001636718
NFE2L3
-0.783951384
3.45681E-10
2.28256E-07
Supplementary Table 3B
SIX4
-0.786068433
1.03296E-08
3.62725E-06
LINGO1
-0.799633257
4.41472E-10
2.69605E-07
RABEPK
-0.800196329
7.90425E-09
3.08398E-06
UAP1
-0.824043651
8.3071E-13
1.29646E-09
BASP1
-0.824097946
1.42052E-09
7.98106E-07
CDK15
-0.8422545
1.07177E-11
1.158E-08
ADAM19
-0.846120742
1.30861E-06
0.000248388
GPR1
-0.853316906
7.60446E-08
2.05408E-05
PLXNB3
-0.870070489
2.72313E-09
1.36546E-06
KIAA1462
-0.878292752
2.2431E-07
5.25109E-05
MYRIP
-0.897493144
1.07803E-12
1.5142E-09
ANKFN1
-0.899481869
5.75088E-07
0.000118789
SEMA6B
-0.907557468
2.09422E-08
6.68534E-06
USMG5
-0.941816931
1.14731E-18
5.37173E-15
USH1C
-0.962877589
1.21873E-07
3.00321E-05
NAT16
-0.972059149
4.3972E-08
1.30969E-05
RHBG
-1.013298074
2.49676E-08
7.79321E-06
METTL9
-1.030072641
3.39804E-14
6.81842E-11
HS3ST3A1
-1.051996657
5.1111E-11
4.48691E-08
RNF11
-1.192395522
6.74941E-22
9.48022E-18
NNT
-1.335737567
2.08051E-13
3.65286E-10
Gene
log2 Fold Change KD shRNA vs SCR shRNA
p value
q value
PAG1
0.922963685
3.59096E-07
1.18855E-12
LRRC19
0.612820719
1.93025E-06
1.18855E-12
FLJ36777
0.53515861
0.002720375
0.000102951
MIR30A
0.491980816
2.16694E-05
6.25969E-11
MAP3K7CL
0.455497596
0.008864981
0.001233905
AGPAT9
0.426596178
0.005470306
0.000437182
TOB1-AS1
0.424577398
0.012176789
0.002685871
LOC102546294
0.416840189
0.015880389
0.004944718
HNRNPH2
0.416450686
0.015703784
0.004922055
MRVI1
0.38349567
0.028211527
0.014027222
OXCT1-AS1
0.377560899
0.028736809
0.014536857
DNAH17-AS1
0.376939137
0.038228442
0.023347948
LOC101927482
0.37279889
0.029301462
0.015139944
TMEM27
0.36469166
0.034590982
0.020564754
SNORD56
0.361375391
0.013589884
0.003519753
ZMYND12
0.360175385
0.039033123
0.02415184
RPP21
0.35779367
0.014347098
0.004064221
CFD
0.356412208
0.050482853
0.037597227
EVI2A
0.355319362
5.46757E-05
9.94986E-10
DHRS2
0.349121289
0.052839644
0.040072093
KLHL29
0.347924949
0.041412922
0.027579562
LOC100506023
0.347404148
0.055390582
0.043898698
LOC100288842
0.336063684
0.022815615
0.009868025
PRIMA1
0.33263901
0.050862553
0.037849115
GIPC2
0.318119744
0.057966443
0.047702294
MBOAT1
0.317049219
0.044522848
0.03114562
KCNN2
0.316723437
0.019130807
0.007161549
IFI27L2
0.314031426
0.030406681
0.015796429
LOC100128568
0.309623899
0.040639045
0.026388408
LUM
0.307710987
0.029093526
0.014950075
SPATA12
0.305674434
0.054742649
0.042903917
ZBTB42
0.304157315
0.037958504
0.023347948
DENND5B-AS1
0.299255963
0.016876204
0.005352566
C15orf38-AP3S2
0.293687827
0.032084415
0.017576687
CTF1
0.287930437
0.058573172
0.048541296
LACTB2-AS1
0.283455424
0.005183491
0.000419307
CIDEB
0.274631471
0.023699386
0.010331414
RPL41
0.269248114
0.030030805
0.015538175
LRP1B
0.266774653
0.051107393
0.038006822
LINC01108
0.262559086
0.055193056
0.043631188
LOC439994
0.259761615
0.040718778
0.026388408
SPRYD4
0.257010204
0.015764599
0.004922055
SLC39A11
0.254822509
0.055682845
0.044162631
MCTP1
0.251502657
0.018877004
0.006980542
PALMD
0.250883466
0.050958639
0.037849115
SYP
0.25037673
0.040671083
0.026388408
ULBP1
0.243470563
0.053773876
0.041491298
NEK7
0.242325668
0.041951421
0.028489075
OXCT1
0.236869688
0.044214553
0.03114562
UBE2V1
0.235145801
0.02327178
0.010230316
GCNT1
0.222076804
0.052755223
0.040043735
IPP
0.219147644
0.03821867
0.023347948
EIF4E3
0.219037133
0.043522905
0.030636982
DHFRL1
0.216899876
0.022378488
0.009536317
H1F0
0.216390215
0.0391133
0.02415184
STX10
0.215862429
0.033900656
0.019652053
MVB12A
0.210255131
0.057932256
0.047702294
LIAS
0.206217317
0.051565446
0.03853314
CFDP1
0.205600558
0.017917354
0.006058174
FUT11
0.205440062
0.053139102
0.04041915
LINC01249
0.204685473
0.053288466
0.040592472
RPUSD3
0.202870628
0.027084724
0.012975545
TCN1
0.20167018
0.005110315
0.000419307
C15orf27
0.190901221
0.026425217
0.012638337
C9orf40
0.18995916
0.025902497
0.012262875
TMEM101
0.185293794
0.047508275
0.033310378
SLC25A48
0.181902166
0.026917564
0.012892514
SPTY2D1
0.17734588
0.020252885
0.007525648
LCLAT1
0.176846194
0.048698723
0.035028452
CDCA4
0.174916638
0.046324217
0.032695147
NSUN3
0.174118623
0.035415164
0.021442113
LRRC7
0.173789434
0.015245721
0.004612919
RAB13
0.163267759
0.047484968
0.033310378
DHFR
0.161618689
0.042633026
0.029431019
MYO1D
0.159225446
0.039384463
0.024470139
EIF3J-AS1
0.1583085
0.058081061
0.047702294
FAM20B
0.145125488
0.045864587
0.032322417
LGALS3
0.138138996
0.028227591
0.014027222
G3BP2
0.137087002
0.026800165
0.012892514
ITGAX
0.130955312
0.055704246
0.044162631
MRPL22
0.12803647
0.054501503
0.042680859
C2orf88
0.120676356
0.02555943
0.012009553
C6
0.100356484
0.048832167
0.035155931
KRT38
0.097390291
0.043871246
0.030636982
LOC101927926
0.095872076
0.038189467
0.023347948
LINC01215
0.088617824
0.049360066
0.035965553
LOC101927285
-0.09961036
0.022599791
0.009704973
LOC100144595
-0.133631587
0.04441406
0.03114562
ZC3HC1
-0.1337447
0.050313073
0.037546911
ANKRD62P1- PARP4P3
-0.137498722
0.048598705
0.034971679
NOMO1
-0.139838945
0.049835564
0.036670996
OPCML
-0.140331825
0.053833259
0.041491298
WDR45
-0.141400001
0.043695613
0.030636982
ANKRD10
-0.142295751
0.038491433
0.023598529
CTNNA1
-0.145772443
0.045649344
0.032234797
POU6F1
-0.159009836
0.059033235
0.049007404
EHD4
-0.165197365
0.037459267
0.023234751
ZXDC
-0.167856226
0.043785279
0.030636982
WDR19
-0.180732699
0.046884277
0.03277974
LOC650226
-0.184870592
0.037345064
0.02317222
COTL1
-0.187295152
0.046150649
0.032491318
NGF
-0.190570223
0.046796916
0.032751312
HDAC9
-0.194872835
0.019944616
0.007280366
LINC01461
-0.200178236
0.047344414
0.033310378
TSTD2
-0.203090059
0.000492572
7.51596E-07
LOC101928307
-0.206526135
0.004306283
0.000342047
PRG2
-0.208843565
0.016935882
0.005352566
PDK3
-0.20901309
0.054342343
0.042481722
FAM124B
-0.213022439
0.036047545
0.022101759
C11orf45
-0.214602111
0.046406016
0.032709644
TXK
-0.215703629
0.037241585
0.02317222
NKTR
-0.215780944
0.036561446
0.022478415
HSPB3
-0.216955329
0.050962483
0.037849115
PEAK1
-0.22095597
0.05174136
0.038760256
RPS6KC1
-0.223482955
0.008085316
0.000983621
LAMA2
-0.225480292
0.058164554
0.047731676
USP34
-0.225948829
0.045500177
0.032109909
TNRC6C
-0.226546766
0.051995203
0.039159188
PCDHB8
-0.228649076
0.058897448
0.049007404
ZNF653
-0.23155931
0.057670782
0.047405262
SLC51B
-0.23604596
0.04551301
0.032109909
PBLD
-0.239042045
0.048254642
0.034556275
COL6A2
-0.23935149
0.046040618
0.032419111
SYNE2
-0.240403854
0.036090447
0.022101759
CHADL
-0.240559921
0.04541016
0.032109909
PARVA
-0.241122296
0.037814418
0.023347948
PLEKHH1
-0.241169948
0.055957206
0.044204248
CEP95
-0.244337751
0.01790992
0.006058174
PCDHGB4
-0.244656367
0.059318509
0.049482729
SRGAP1
-0.244692824
0.052208547
0.039470544
LOC146880
-0.247626908
0.046673166
0.032751312
DNM3OS
-0.248968848
0.004924791
0.000419307
DYNC2H1
-0.250011021
0.05602147
0.044204248
UTRN
-0.251506423
0.051211838
0.038076921
SEMA3G
-0.252903462
0.026571066
0.012724545
AEBP1
-0.253179042
0.029844498
0.015538175
IPW
-0.253514177
0.016844343
0.005352566
DPY19L2
-0.254920522
0.024091969
0.01061904
LINC01239
-0.255127158
0.050686855
0.037849115
LTBP1
-0.256529094
0.004672361
0.000413142
SPP1
-0.257970302
0.038021365
0.023347948
LOC100129550
-0.258779822
0.047386083
0.033310378
FAM117B
-0.258976801
0.008040006
0.000983621
L3MBTL1
-0.26190691
0.045796234
0.032322417
ZNF208
-0.262893055
0.023930888
0.010520777
VPS13D
-0.263240714
0.050747736
0.037849115
CLCN6
-0.266043675
0.055202928
0.043631188
RBMS3
-0.269945181
0.014721024
0.004308479
PCDHA9
-0.270198906
0.021332561
0.008572439
LOC440982
-0.271264841
0.032967571
0.018687829
FLRT2
-0.271608743
0.053002981
0.040275599
KIAA0226L
-0.274653216
0.049724002
0.036588427
PPP3R2
-0.274674803
0.059051084
0.049007404
CHSY3
-0.275838137
0.055733761
0.044162631
ACTA2
-0.277633844
0.04309727
0.030007826
TPTE
-0.278423442
0.037089502
0.023147156
HUWE1
-0.279358357
0.058017492
0.047702294
CYP2E1
-0.280986411
0.052475621
0.039584269
COL6A1
-0.283183834
0.054641467
0.042836561
LOC101928323
-0.283644537
0.058917263
0.049007404
CD101
-0.284007048
0.048574916
0.034971679
MRPS31P5
-0.285703667
0.036368263
0.02242285
RYR2
-0.286100951
0.023638099
0.010331414
COLQ
-0.287357308
0.038521567
0.023598529
DMD
-0.288680924
0.044780203
0.031386013
POU2F1
-0.288917145
0.031709068
0.017233977
KALRN
-0.290277332
0.036109577
0.022101759
AFG3L1P
-0.291907712
0.030630892
0.015796429
ZNF286B
-0.29331278
0.037684631
0.023347948
HERC2P4
-0.295624049
0.042488458
0.029411855
FRMD3
-0.296504278
0.003677761
0.000229949
RNF213
-0.296639061
0.046690641
0.032751312
LINC00310
-0.296837674
0.016458615
0.005234614
GSDMB
-0.296872076
0.057378817
0.047050854
LPXN
-0.297268286
0.016236562
0.005109174
SVEP1
-0.297287351
0.03730122
0.02317222
IDH1-AS1
-0.297363747
0.043680474
0.030636982
OR2F1
-0.2979349
0.023657058
0.010331414
HBEGF
-0.298871268
0.047210145
0.033299029
HERC1
-0.300714423
0.04797921
0.034133625
MIR600HG
-0.303578674
0.046564236
0.032751312
RAB31
-0.304570057
0.033106877
0.018723435
DYNC1H1
-0.305061922
0.046752173
0.032751312
STARD9
-0.307091184
0.024434833
0.010827321
C1orf167
-0.307892525
0.043017164
0.030005596
HECTD4
-0.310726695
0.026128514
0.012460571
KLHL4
-0.311214425
0.033834649
0.019652053
CFAP44
-0.311348547
0.013153606
0.003320399
LOC101927391
-0.313651651
0.056568122
0.045306176
GRK4
-0.318791089
0.016912
0.005352566
SCN1A
-0.32072469
0.031019005
0.016270811
GPR75
-0.32264214
0.04591856
0.032322417
ZDHHC11
-0.323069891
0.004917445
0.000419307
ACP5
-0.323346927
0.024506614
0.010827321
TRPV1
-0.323909404
0.008039478
0.000983621
ATP10A
-0.325064816
0.033438973
0.019144679
FAT1
-0.325729481
0.029861134
0.015538175
CXCL14
-0.328423567
0.044586412
0.03114562
LINC00202-2
-0.328472898
0.030142058
0.015542747
FLG-AS1
-0.331614925
0.055938407
0.044204248
DST
-0.332088409
0.010518958
0.001841208
RASGRF2
-0.332120848
0.040235519
0.025911685
ADGB
-0.334430061
0.005038477
0.000419307
IGFALS
-0.334742154
0.039133537
0.02415184
SMG1
-0.334968335
0.019855891
0.007280366
PCDH17
-0.337204457
0.025635549
0.012009553
USP32P2
-0.339749701
0.019406971
0.007163797
CLEC2D
-0.339829939
0.017178205
0.005501014
DGKH
-0.340297155
0.052397283
0.039569596
LOC100506124
-0.340482209
0.049108883
0.035586716
GAB3
-0.342672996
0.045391115
0.032109909
PDE5A
-0.343363181
0.005647091
0.000447311
PDLIM1
-0.343597663
0.055790637
0.044162631
MYLK
-0.343879737
0.005415077
0.000437182
PTOV1-AS1
-0.343883113
0.03524978
0.021395879
CRIPAK
-0.344547847
0.022252749
0.009490262
MUC20
-0.345473344
0.019222985
0.007163018
SCN9A
-0.34662102
0.057466049
0.047087575
SGK494
-0.347473714
0.035307024
0.021395879
FBXL21
-0.34889163
0.005012418
0.000419307
PKI55
-0.349264393
0.05046487
0.037597227
PTCH2
-0.349775682
0.045009063
0.031699682
ZNF540
-0.351148848
0.042656233
0.029431019
SRRM4
-0.351663107
0.011305939
0.002192449
CEBPD
-0.352917759
0.044471066
0.03114562
SFRP4
-0.353364453
0.052372546
0.039569596
HCN1
-0.354724925
0.032065205
0.017576687
MTTP
-0.355403608
0.051354664
0.038230752
IL4I1
-0.356932511
0.026270991
0.012540813
DNHD1
-0.359480179
0.021282429
0.008572439
ADGRG1
-0.360549493
0.027851612
0.013843904
RUNX1T1
-0.361741635
0.005392784
0.000437182
SNRK-AS1
-0.361980713
0.038188926
0.023347948
SMIM17
-0.362330777
0.033003746
0.018687829
FAR2P1
-0.364086639
0.044433552
0.03114562
LYG1
-0.365128345
0.029806655
0.015538175
HMCN1
-0.36587039
0.035100904
0.021323169
FMN1
-0.367719966
0.043874627
0.030636982
HNRNPU-AS1
-0.367751957
0.026942619
0.012892514
IFITM2
-0.37206973
0.024869464
0.011196374
MAP2
-0.372274477
0.036921253
0.022987099
DNAJC15
-0.372886745
0.0389168
0.02415184
KLKB1
-0.373000009
0.029894185
0.015538175
RUNX1
-0.374529132
0.030605355
0.015796429
AGT
-0.376065563
0.019921807
0.007280366
PHEX
-0.37647032
0.024284102
0.010758912
THSD1
-0.376631368
0.008257927
0.001020541
KHDC1
-0.378596959
0.038149179
0.023347948
NEB
-0.37884558
0.033995357
0.019674258
PYGM
-0.380270814
0.036455789
0.022433902
GALNT3
-0.380624629
0.030057531
0.015538175
PCDHGA10
-0.382438236
0.036036303
0.022101759
CFAP47
-0.384093868
0.032332408
0.017847704
MARCH10
-0.3855816
0.027942978
0.013854415
ACTG2
-0.391306317
0.03049252
0.015796429
UG0898H09
-0.396061696
0.028402001
0.014161905
LOC102724890
-0.397039577
0.027825104
0.013843904
LINC01337
-0.401564459
0.019327656
0.007163797
IL17B
-0.403321609
0.013344278
0.003398214
AGPAT4-IT1
-0.407989736
0.014814628
0.004310088
FN3K
-0.410044666
0.023076858
0.010091562
NELL2
-0.412183847
0.006494158
0.00061319
ZNF90
-0.413760099
0.023445697
0.010331414
SEMA6A-AS1
-0.417981728
0.011056796
0.002094253
LINC01004
-0.418332894
0.019578957
0.007163797
SLC13A5
-0.418477488
0.021914729
0.009176936
MUCL1
-0.418850026
0.007850538
0.000983621
NPIPB4
-0.419435333
0.005639869
0.000447311
RHPN1-AS1
-0.426272458
0.019548344
0.007163797
PITX2
-0.428057386
0.016078399
0.00504525
LRRC3B
-0.428588228
0.00926441
0.001375844
ADGRV1
-0.436666903
0.000271548
1.3211E-07
GTSF1
-0.442421232
0.006004992
0.000520865
UNC5C
-0.464547124
0.01048731
0.001841208
FN1
-0.46740212
0.003703526
0.000229949
FAT4
-0.471025872
0.009823221
0.00156647
PCDHGA5
-0.473251816
0.009544251
0.001469787
LRRC70
-0.474788669
0.008088762
0.000983621
S100A10
-0.481139441
0.006491744
0.00061319
SPTBN5
-0.485013534
0.007871563
0.000983621
MSH5-SAPCD1
-0.490386257
0.006543624
0.00061319
KCND2
-0.517020462
0.001161919
9.70578E-06
KCNQ1OT1
-0.55680171
0.002258799
6.29538E-05
NANOS1
-0.568628778
0.001750595
3.13104E-05
FAM133CP
-0.578109116
1.52287E-05
2.47218E-11
PEX5L
-0.855451164
4.604E-09
1.18855E-12
NNT
-1.65327293
1.24657E-19
1.18855E-12
Supplementary Table 4. A-B: Significantly (p<0.01) dysregulated pathways comparing KD siRNA cells to SCR siRNA cells (4A) and KD shRNA cells to SCR shRNA cells (4B). C: Gene expression changes within the 'Protein Processing in the Endoplasmic Reticulum' KEGG pathway, comparing KD shRNA cells to SCR shRNA cells. Supplementary Table 4A
Pathway (KD siRNA vs SCR siRNA)
p value
q value
up-regulated genes
down- regulated genes
hsa03040 Spliceosome
5.42948E-06
0.000782253
94
-32
hsa03010 Ribosome
7.59468E-06
0.000782253
97
-29
hsa03013 RNA transport
1.51944E-05
0.00104335
105
-36
hsa04115 p53 signaling pathway
0.000170523
0.015091608
30
-32
hsa04010 MAPK signaling pathway
0.000171555
0.015091608
109
-111
hsa04360 Axon guidance
0.000219781
0.015091608
69
-68
hsa04710 Circadian rhythm
0.000815962
0.042022043
13
-15
hsa04110 Cell cycle
0.000957167
0.049294082
79
-39
hsa04114 Oocyte meiosis
0.001315026
0.051042169
65
-30
hsa03008 Ribosome biogenesis in eukaryotes
0.001486665
0.051042169
52
-18
hsa03015 mRNA surveillance pathway
0.002031137
0.059773455
54
-25
hsa04150 mTOR signaling pathway
0.00259412
0.06679858
85
-45
hsa04068 FoxO signaling pathway
0.001990434
0.072315727
61
-52
hsa04151 PI3K-Akt signaling pathway
0.002106283
0.072315727
118
-107
hsa04014 Ras signaling pathway
0.002689978
0.079162207
79
-71
hsa03030 DNA replication
0.006003215
0.11408099
27
-8
hsa03460 Fanconi anemia pathway
0.006150791
0.11408099
36
-12
hsa04120 Ubiquitin mediated proteolysis
0.006580001
0.11408099
89
-42
hsa03018 RNA degradation
0.006645495
0.11408099
52
-22
hsa04140 Regulation of autophagy
0.008136037
0.123597863
72
-46
hsa00970 Aminoacyl-tRNA biosynthesis
0.008399855
0.123597863
28
-16
hsa04390 Hippo signaling pathway
0.005437739
0.140021788
54
-67
Supplementary Table 4B
Supplementary Table 4C
Pathway (KD shRNA vs SCR shRNA)
p.val
q.val
Up-regulated genes
Down- regulated genes
hsa03010 Ribosome
1.04416E-05
0.002150972
98
-34
hsa03040 Spliceosome
0.001103391
0.113235169
84
-46
hsa04141 Protein processing in endoplasmic reticulum
0.001649056
0.113235169
102
-59
hsa00983 Drug metabolism - other enzymes
0.005443889
0.229149376
25
-10
hsa00240 Pyrimidine metabolism
0.005561878
0.229149376
65
-34
hsa00190 Oxidative phosphorylation
0.00993535
0.341113698
68
-47
Gene
Log2fold change KD shRNA vs SCR shRNA
p value
q value
AMFR
0.029120894
0.692680229
0.923307833
ATF4
-0.038779036
0.749485377
0.954539392
ATF6
0.011596787
0.894351109
0.994260181
ATF6B
0.021001096
0.781540675
0.976327549
ATXN3
-0.013868658
0.878327015
0.993017965
BAG1
0.036172831
0.763954601
0.963331979
BAG2
0.094784169
0.585576621
0.83898096
BAK1
0.086045716
0.403960204
0.611763447
BAX
0.154032462
0.118575863
0.145116226
BCAP31
0.051863741
0.531856228
0.774625038
BCL2
0.264732307
0.063414339
0.054909291
CALR
0.041508948
0.633471971
0.8781132
CANX
0.062913422
0.409500979
0.619405643
CAPN1
-0.000619529
0.994582708
1
CAPN2
0.062333279
0.472683232
0.703888616
CKAP4
0.033468944
0.754032405
0.955323467
CRYAB
-0.07853826
0.66601657
0.904603198
CUL1
-0.070065107
0.416543969
0.62780944
DAD1
-0.005456425
0.947446795
1
DDIT3
0.016955951
0.925816883
1
DDOST
0.074300928
0.315038287
0.47954916
DERL1
0.02177722
0.761535097
0.961247176
DERL2
0.02130004
0.747894859
0.953932446
DERL3
0.125943444
0.483678768
0.716996125
DNAJA1
0.026895612
0.846239555
0.993017965
DNAJA2
0.034288294
0.653996117
0.895577112
DNAJB1
0.019377577
0.855982505
0.993017965
DNAJB11
0.045474053
0.573816699
0.826548807
DNAJB12
-0.051777694
0.557169975
0.806207111
DNAJB2
0.127391544
0.210599576
0.29968158
DNAJC1
0.208341418
0.071374842
0.063696747
DNAJC10
-0.03392065
0.6074001
0.859987994
DNAJC3
0.03564692
0.638573891
0.88182883
DNAJC5
0.058052695
0.373352077
0.563225419
DNAJC5B
-0.005691453
0.841974099
0.993017965
DNAJC5G
0.028958158
0.753369557
0.95466863
EDEM1
-0.029555307
0.779016203
0.974083751
EDEM2
0.040029532
0.642439254
0.885189529
EDEM3
-0.033780382
0.742804483
0.95228687
EIF2AK1
-0.011811788
0.849785813
0.993017965
EIF2AK2
0.072101074
0.501691058
0.73976841
EIF2AK3
-0.050681638
0.487351497
0.720265345
EIF2AK4
0.015797672
0.825704713
0.993017965
EIF2S1
0.008872628
0.907393451
0.999456943
ERLEC1
0.034950188
0.675729634
0.913887439
ERN1
0.084514189
0.457532042
0.685291886
ERO1A
0.12521397
0.259085879
0.389646236
ERO1B
0.025408659
0.805929681
0.993017965
ERP29
0.079287044
0.462056315
0.69037553
FBXO2
-0.013466883
0.941123962
1
FBXO6
-0.045909183
0.668014318
0.905945065
GANAB
0.056723727
0.435820189
0.653217036
HERPUD1
-0.008613719
0.935825808
1
HSP90AA1
0.049457951
0.6959656
0.923307833
HSP90AB1
0.027239569
0.734677206
0.951441751
HSP90B1
0.034458995
0.698058433
0.924409218
HSPA1A
-0.006797184
0.965327355
1
HSPA1B
0.090466711
0.363409827
0.549969177
HSPA1L
0.11312329
0.443397447
0.663627153
HSPA2
-0.037981621
0.745043223
0.95228687
HSPA4L
-0.004670522
0.963538567
1
HSPA5
0.046658057
0.504077511
0.742899748
HSPA6
-0.127562115
0.412822443
0.62288389
HSPA8
0.065215999
0.638611585
0.88182883
HSPBP1
0.000887396
0.993688187
1
HSPH1
0.019896432
0.878338747
0.993017965
HYOU1
0.043969168
0.459618516
0.688000682
LMAN1
0.050698474
0.54194916
0.789328352
LMAN1L
0.139561888
0.381858555
0.577168278
LMAN2
0.120650764
0.16488796
0.220413878
MAN1A1
-0.059559597
0.689496573
0.922591082
MAN1A2
0.073376513
0.390064306
0.589383219
MAN1B1
0.035607125
0.724636496
0.943578581
MAN1C1
-0.005119397
0.97149816
1
MAP2K7
0.12186443
0.369707866
0.557481343
MAP3K5
-0.122240346
0.403909705
0.611763447
MAPK10
-0.158493298
0.177231713
0.242838509
MAPK8
-0.011912116
0.893714501
0.994107865
MAPK9
-0.017925903
0.777676134
0.97385499
MARCH6
-0.051123261
0.492734682
0.727072243
MBTPS1
-0.051666244
0.517443442
0.756981957
MBTPS2
0.079209414
0.446740087
0.667852591
MOGS
0.121293355
0.256380469
0.386111655
NFE2L2
-0.042174373
0.705215433
0.929482314
NGLY1
0.01489591
0.880649163
0.993017965
NPLOC4
-0.040005858
0.660166539
0.897674496
NSFL1C
0.083690553
0.275362568
0.41614581
OS9
0.054138039
0.476595319
0.707696985
P4HB
0.116021915
0.127071861
0.159405719
PARK2
-0.046058773
0.787567574
0.981106444
PDIA3
0.053520403
0.48750727
0.720265345
PDIA4
0.032534269
0.744295685
0.95228687
PDIA6
0.021028668
0.769691785
0.967111581
PLAA
0.035249955
0.642720433
0.885460651
PPP1R15A
0.105426696
0.470330781
0.701262454
PREB
0.001220953
0.987458323
1
PRKCSH
0.04564895
0.573342312
0.826057887
RAD23A
0.084598367
0.336763602
0.510899339
RAD23B
0.058327984
0.306234455
0.464872169
RBX1
-0.090956466
0.282067705
0.427201992
RNF5
0.249909325
0.167614943
0.224458263
RPN1
-0.00840644
0.912798848
1
RPN2
-0.010289403
0.90753017
0.999456943
RRBP1
-0.044216132
0.590373232
0.84305055
SAR1A
-0.009191662
0.903865087
0.997893009
SAR1B
-0.012020133
0.850266483
0.993017965
SEC13
0.038741149
0.575308486
0.828576978
SEC23A
-0.008835874
0.926486277
1
SEC23B
-0.019503886
0.824832001
0.993017965
SEC24A
-0.02802575
0.809661788
0.993017965
SEC24B
-0.109016005
0.181150499
0.248166155
SEC24C
-0.02074248
0.79923445
0.989170476
SEC24D
0.06699759
0.428207736
0.642909201
SEC31A
-0.048936166
0.467517817
0.697359546
SEC31B
-0.015252849
0.899591629
0.99619613
SEC61A1
0.015760673
0.804192011
0.992852481
SEC61A2
-0.126420437
0.182351406
0.250856876
SEC61B
0.048406191
0.725665345
0.944183473
SEC61G
0.033188795
0.765804128
0.964873315
SEC62
0.066993131
0.425442981
0.638631164
SEC63
0.017028265
0.819170253
0.993017965
SEL1L
-0.006841532
0.928561892
1
SIL1
0.120190262
0.317505822
0.482601775
SKP1
-0.021639638
0.76726016
0.965886524
SSR1
0.061203562
0.466219741
0.696051077
SSR2
0.02625855
0.737994841
0.95228687
SSR3
0.032178011
0.654125701
0.895577112
SSR4
0.012745906
0.898038942
0.995811867
STT3A
0.036998633
0.658397793
0.897511674
STT3B
0.025926771
0.773037108
0.969430453
STUB1
0.005928304
0.941118859
1
SVIP
0.066199387
0.457313668
0.685165325
SYVN1
0.039574585
0.55950895
0.809143736
TRAF2
-0.016765601
0.881468537
0.993017965
TRAM1
0.032896168
0.728785757
0.946248622
TUSC3
-0.00929134
0.914057929
1
TXNDC5
0.083035209
0.523342805
0.766355471
UBE2D1
-0.125335946
0.276006512
0.417563888
UBE2D2
0.033436207
0.676764495
0.914911246
UBE2D3
0.026529833
0.740844246
0.95228687
UBE2D4
-0.010900293
0.912931061
1
UBE2E1
0.010547037
0.894623851
0.994390931
UBE2E2
0.101797409
0.432129742
0.647776291
UBE2E3
-0.020118927
0.766551781
0.965492779
UBE2G1
0.005878768
0.959889107
1
UBE2G2
-0.021487958
0.79078306
0.982556181
UBE2J1
-0.005258362
0.968385928
1
Supplementary Table 5. Significantly dysregulated (q<0.05) pathways comparing C57BL/6J (Nnt mutant) to C57BL/6N (Nnt wild-type) mice (5A) and C57BL/6J (NNT mutant) to C57BL/6JBAC (transgenic) mice (5B). Pathways that are shared between the two comparisons are highlighted in bold. Supplementary Table 5A
Supplementary Table 6. Intracellular and extracellular metabolome analysis comparing KD siRNA to
SCR siRNA cells (A, B) and KD shRNA to SCR shRNA cells (C, D). Metabolites with q<0.01 and <0.8
or >1.2- fold change are tabulated for the KD siRNA to SCR siRNA comparison. Metabolites with p<0.05
and <0.8 or >1.2-fold change are tabulated for the KD shRNA to SCR shRNA comparison (no
metabolites with q<0.05 for this comparison).
Supplementary Table 6A
Significantly altered (q<0.01) intracellular metabolites (KD siRNA vs SCR siRNA)
Supplementary Table 7. Pathway analysis of intracellular metabolome comparing KD siRNA to SCR
siRNA (6A) and KD shRNA to SCR shRNA cells (6B). p<0.05 was used as the threshold of significance.
Significant metabolites within each pathway are highlighted in bold font.
Supplementary Table 7A
Pathways enriched comparing KD siRNA to SCR siRNA cells
p value
q value
Metabolites in pathway (significant metabolites in bold)
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