Supplementary Material

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Supplementary Material
Ecologically relevant oestrogen pollution affects sex-specific gene expression and delays
sex differentiation in grayling (Salmonidae)
Oliver M. Selmoni1*, Diane Maitre1*, Julien Roux1,2, Laetitia G. E. Wilkins1, Lucas Marques
da Cunha1, Etienne L. M. Vermeirssen3, Susanne Knörr4, Marc Robinson-Rechavi1,2#, Claus
Wedekind1#
1
Department of Ecology and Evolution, Biophore, University of Lausanne, 1015 Lausanne,
Switzerland
2
Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland
3
Swiss Centre for Applied Ecotoxicology Eawag-EPFL, Dübendorf, Switzerland
4
Aquatic Ecology and Toxicology Group, Center of Organismic Studies, University of
Heidelberg, Heidelberg, Germany
* equal contributors
#
shared senior authors
Present addresses:
O. Selmoni: Swiss Federal Institute of Technology (EPFL), Bâtiment GC, 1015 Lausanne,
Switzerland.
L. Wilkins: Department of Environmental Sciences, Policy and Management, 130 Mulford
Hall #3114, University of California, Berkeley, CA 94720, USA
J. Roux: Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel,
Switzerland
Correspondence: Claus Wedekind, [email protected], orcid.org/0000-0001-6143-4716
Content
Supplementary Figures:
Figure S1: EE2 concentrations in EE2-treated 200L tanks over time.
Figure S2: Differential gene expression of control and EE2-treated males or females at different
developmental stages
Figure S3: REVIGO treemap in EE2-treated males at embryo stage: down-regulated genes.
Figure S4: REVIGO treemap in EE2-treated males at embryo stage: up-regulated genes.
Figure S5: REVIGO treemap in EE2-treated males at hatching: down-regulated genes.
Figure S6: REVIGO treemap in EE2-treated males at hatching: up-regulated genes.
Figure S7: REVIGO treemap in EE2-treated females at hatching: down-regulated genes.
Figure S8: REVIGO treemap in EE2-treated females at hatching: up-regulated genes.
Figure S9: REVIGO treemap in EE2-treated females at first feeding: down-regulated genes.
Figure S10: REVIGO treemap in EE2-treated females at first feeding: up-regulated genes.
Figure S11: REVIGO treemap in EE2-treated males and females at hatching: down-regulated genes.
Figure S12: REVIGO treemap in EE2-treated males and females at hatching: up-regulated genes.
Supplementary Tables:
Table S1: Top 25 gene ontology terms enriching the genes of EE2-treated males at embryo stage.
Table S2: Top 25 gene ontology terms enriching the genes of EE2-treated males at hatching.
Table S3: Top 25 gene ontology terms enriching the genes of EE2-treated females at hatching.
Table S4: Top 25 gene ontology terms enriching the genes of EE2-treated females at first feeding.
Table S5: Top 25 gene ontology terms enriching the genes of EE2-treated males and females at
hatching
1
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Figure S1. EE2 concentrations in EE2-treated 200L tanks as set at start (40 dpf, i.e. the day
when fish were transferred into the tanks) and measured in 7-day periods, starting each 1 hour
after the weekly water exchange (20% of the water replaced with fresh lake water at 1 ng/L
EE2; grey boxes and symbols; T0) and 7 days later before the next water exchange (open
boxes and symbols; T7). The grey and open boxes represent medians of monthly means: 4
consecutive T0 and 4 consecutive T7 samples per tank had each been pooled to reduce the
number of analyses to N = 32, i.e. 4 tanks x 4 four-week intervals x 2 time points (with the
last interval being a five-week interval). One unexplained outlier (5.1 ng/L) at T0 of the
second sampling period (75-103 dpf) was excluded from the graph and all analyses. On the
one hand, the value was confirmed both by the analysis of the duplicate sample as well as two
of the weekly samples that made up the pool of the second sampling period. On the other
hand, its corresponding T7 measurement of 0.09 ng/L was very close to the ones of the other 3
tanks, i.e. the outlier is unlikely to reflect the EE2 concentration in the tank and seems instead
be due to accidental contamination of some probes after sampling. Control aquaria were not
spiked with EE2, yet the 15 control samples that were analysed showed unexpected EE2
concentrations of up to 12.8 ng/L, supporting the hypothesis of accidental contamination of
some probes after sampling.
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Figure S2. Differential gene expression of control and EE2-treated males or females at different developmental
stages. The left panels show for each gene the log-fold change in expression between the two conditions of the
contrast (positive: more expressed under control, negative: more expressed under EE2 treatment) and the
average log-expression. Red dots indicate genes who are differentially expressed at q<0.15. The right panels
give the distribution of the p-values associated to the tests of differential expression for each gene (before qvalue correction). A left skew indicates more genes found as differentially expressed than expected by chance. A
flat distribution represents what we would expected if there is no difference in gene expression between the
conditions. A right skew suggests a lack of accuracy (and statistical power) in the model, since fewer genes were
detected as differentially expressed than expect by chance.
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Figure S3 REVIGO treemap (Supek et al., 2011) of the 64 top gene ontology terms enriching
the down-regulated genes (q<0.15) in EE2-treated males at embryo stage. REVIGO clusters
GO terms according to their semantic similarity.
89
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Figure S4 REVIGO treemap (Supek et al., 2011) of the 55 top gene ontology terms
enriching the up-regulated genes (q<0.15) in EE2-treated males at embryo stage.
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Figure S5 REVIGO treemap (Supek et al., 2011) of the 150 top gene ontology terms
enriching the down-regulated genes (q<0.15) in EE2-treated males at hatching.
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Figure S6 REVIGO treemap (Supek et al., 2011) of the 144 top gene ontology terms
enriching the genes up-regulated (q<0.15) in EE2-treated males at hatching.
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Figure S7 REVIGO treemap (Supek et al., 2011) of the 150 top gene ontology terms
enriching the down-regulated genes (q<0.15) in EE2-treated females at hatching. In EE2treated males, these genes were found to be up-regulated or not altered.
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Figure S8 REVIGO treemap of the 150 top gene ontology terms enriching the up-regulated
genes (q<0.15) in EE2-treated females at hatching. In EE2-treated males, these genes were
found to be down-regulated or not altered.
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95
96
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Figure S9 REVIGO treemap of the 150 top gene ontology terms enriching the downregulated genes (q<0.15) in EE2-treated females at first feeding.
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Figure S10 REVIGO treemap of the 150 top gene ontology terms enriching the upregulated genes (q<0.15) in EE2-treated females at first feeding.
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Figure S11 REVIGO treemap of the 37 top gene ontology terms enriching the downregulated genes (q<0.15) in EE2-treated males and females at hatching.
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Figure S12 REVIGO treemap of the 63 top gene ontology terms enriching the up-regulated
genes (q<0.15) in EE2-treated males and females at hatching.
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106
107
Table S1 Top 25 gene ontology (GO) terms enriching the down- or up-regulated genes in
EE2-treated males at embryo stage (see Fig. S3a).
GO
identifier
p-value
In DE
In ALL
Biological process
a) Down regulated
GO:0006313
GO:0015074
GO:0016925
GO:0006357
GO:0042051
GO:0006595
GO:0031099
GO:0021554
GO:0033962
GO:0030512
3.29E-07
1.61E-05
7.10E-04
1.17E-03
2.67E-03
4.26E-03
6.34E-03
6.80E-03
6.84E-03
7.62E-03
24
26
3
13
2
2
2
2
2
2
486
724
14
382
6
8
10
10
10
11
GO:1902354
1.20E-02
1
1
GO:1902355
1.20E-02
1
1
GO:2000727
GO:1901097
GO:1902902
GO:0006810
GO:0051726
GO:0001541
GO:0007049
GO:1903507
GO:0046847
GO:0045666
GO:0051307
GO:1901970
GO:0060838
1.21E-02
1.21E-02
1.21E-02
1.29E-02
1.35E-02
1.36E-02
1.48E-02
1.53E-02
1.76E-02
1.93E-02
2.27E-02
2.27E-02
2.39E-02
1
1
1
6
5
1
5
2
2
2
1
1
1
1
1
1
151
109
1
111
15
16
17
2
2
2
transposition, DNA-mediated
DNA integration
protein sumoylation
regulation of transcription from RNA polymerase II promoter
compound eye photoreceptor development
polyamine metabolic process
regeneration
optic nerve development
cytoplasmic mRNA processing body assembly
negative regulation of transforming growth factor beta receptor signalling
pathway
blood vessel endothelial cell delamination involved in blood vessel lumen
ensheathment
endothelial tube lumen extension involved in blood vessel lumen
ensheathment
positive regulation of cardiac muscle cell differentiation
negative regulation of autophagosome maturation
negative regulation of autophagosome assembly
transport
regulation of cell cycle
ovarian follicle development
cell cycle
negative regulation of nucleic acid-templated transcription
filopodium assembly
positive regulation of neuron differentiation
meiotic chromosome separation
positive regulation of mitotic sister chromatid separation
lymphatic endothelial cell fate commitment
b) Up regulated
GO:0035493
0.006415202 1
1
SNARE complex assembly
GO:0033628
0.006449291 1
1
regulation of cell adhesion mediated by integrin
GO:0052697
0.006483679 1
1
xenobiotic glucuronidation
GO:0009436
0.006507012 1
1
glyoxylate catabolic process
GO:0019752
0.009775613 2
22
carboxylic acid metabolic process
GO:0002761
0.012789556 1
2
regulation of myeloid leukocyte differentiation
GO:0031639
0.012823452 1
2
plasminogen activation
GO:0061075
0.013282008 1
2
positive regulation of neural retina development
GO:0072657
0.014083493 1
2
protein localization to membrane
GO:0043009
0.015823139 5
215
chordate embryonic development
GO:0021982
0.019123174 1
3
pineal gland development
GO:0042542
0.019123348 1
3
response to hydrogen peroxide
GO:0008637
0.019201954 1
3
apoptotic mitochondrial changes
GO:0043029
0.019636776 1
3
T cell homeostasis
GO:0050856
0.019636776 1
3
regulation of T cell receptor signalling pathway
GO:0000184
0.0198528
2
32
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
GO:0048069
0.020429941 1
3
eye pigmentation
GO:0032880
0.02169454 1
3
regulation of protein localization
GO:0051302
0.02169454 1
3
regulation of cell division
GO:0021628
0.02541896 1
4
olfactory nerve formation
GO:0071699
0.02541896 1
4
olfactory placode morphogenesis
GO:0019369
0.025419294 1
4
arachidonic acid metabolic process
GO:0042730
0.025773572 1
4
fibrinolysis
GO:0017183
0.026358114 1
4
peptidyl-diphthamide biosynthetic process from peptidyl-histidine
GO:0006424
0.02644536 1
4
glutamyl-tRNA aminoacylation
GO terms ranked according to p-value. In DE = number of down- or up-regulated genes (q<0.15); In All = total number of genes
carrying the term.
108
14
109
110
111
Table S2 Top 25 GO-terms enriching the down- or up-regulated genes in EE2-treated males
at hatching (see Fig. S3c).
GO
identifier
p-value
In DE
In ALL
Biological process
3.39E-08
1.01E-07
2.48E-07
2.33E-06
2.34E-05
5.20E-05
6.24E-05
1.55E-04
2.85E-04
2.90E-04
3.16E-04
3.22E-04
3.70E-04
5.63E-04
7.09E-04
7.14E-04
7.14E-04
8.24E-04
8.81E-04
8.85E-04
9.42E-04
1.01E-03
1.18E-03
1.18E-03
1.22E-03
9
27
76
42
8
15
20
9
14
4
91
5
9
25
23
14
10
10
8
15
8
26
20
4
13
10
62
294
139
11
35
54
16
35
4
443
6
17
89
80
38
23
24
17
43
16
96
68
5
33
regulation of striated muscle contraction
skeletal muscle tissue development
cell adhesion
actin cytoskeleton organization
glycogen catabolic process
myofibril assembly
skeletal muscle fiber development
protein localization to plasma membrane
muscle fiber development
peptidyl-lysine dimethylation
intracellular protein transport
negative regulation of histone methylation
muscle attachment
cellular calcium ion homeostasis
canonical Wnt signaling pathway
sarcomere organization
regulation of axon extension
muscle cell cellular homeostasis
fructose 6-phosphate metabolic process
cell morphogenesis
glycogen biosynthetic process
convergent extension involved in gastrulation
locomotory behavior
histone H3-K36 methylation
fin development
a) Down regulated
GO:0006942
GO:0007519
GO:0007155
GO:0030036
GO:0005980
GO:0030239
GO:0048741
GO:0072659
GO:0048747
GO:0018027
GO:0006886
GO:0031061
GO:0016203
GO:0006874
GO:0060070
GO:0045214
GO:0030516
GO:0046716
GO:0006002
GO:0000902
GO:0005978
GO:0060027
GO:0007626
GO:0010452
GO:0033333
b) Up regulated
GO:0010499
GO:0006313
GO:0006412
GO:0006281
GO:0015074
GO:0043161
GO:0006777
GO:0051301
GO:0006355
GO:0000724
GO:0006367
GO:0097502
GO:0042073
GO:0006122
GO:0006828
GO:0007195
GO:0032099
GO:0021575
GO:0006807
GO:0009186
GO:0007067
GO:0016578
GO:0042384
GO:0000398
1.15E-10
1.15E-09
4.37E-09
4.85E-07
1.41E-04
1.57E-04
3.33E-04
4.22E-04
4.32E-04
4.99E-04
6.36E-04
8.67E-04
1.49E-03
1.53E-03
1.94E-03
2.20E-03
2.28E-03
2.36E-03
2.41E-03
2.61E-03
2.85E-03
2.88E-03
2.91E-03
3.08E-03
23
141
82
46
166
44
11
38
261
13
10
4
8
9
5
5
5
8
5
5
27
6
38
28
34
486
256
134
724
150
21
130
1276
32
20
4
15
18
7
7
7
16
7
7
93
10
144
99
proteasomal ubiquitin-independent protein catabolic process
transposition, DNA-mediated
translation
DNA repair
DNA integration
proteasome-mediated ubiquitin-dependent protein catabolic process
Mo-molybdopterin cofactor biosynthetic process
cell division
regulation of transcription, DNA-templated
double-strand break repair via homologous recombination
transcription initiation from RNA polymerase II promoter
mannosylation
intraciliary transport
mitochondrial electron transport, ubiquinol to cytochrome c
manganese ion transport
adenylate cyclase-inhibiting dopamine receptor signaling pathway
negative regulation of appetite
hindbrain morphogenesis
nitrogen compound metabolic process
deoxyribonucleoside diphosphate metabolic process
mitotic nuclear division
histone deubiquitination
cilium assembly
mRNA splicing, via spliceosome
GO:0045116
3.80E-03
8
17
protein neddylation
GO terms ranked according to p-value. In DE = number of down- or up-regulated genes (q<0.15); In All = total number of genes
carrying the term.
112
15
113
114
115
Table S3 Top 25 GO-terms enriching the down- or up-regulated genes in EE2-treated females
at hatching (see Fig. S3d).
GO
identifier
p-value
In DE
In ALL
Biological process
4.32E-27
1.73E-19
1.85E-19
1.60E-07
1.85E-04
3.65E-04
5.18E-04
8.55E-04
8.99E-04
9.88E-04
1.10E-03
1.12E-03
1.20E-03
1.28E-03
1.50E-03
1.56E-03
1.58E-03
1.58E-03
1.92E-03
2.10E-03
2.33E-03
2.55E-03
2.76E-03
2.97E-03
3.03E-03
280
358
157
70
65
9
7
17
14
60
14
14
27
9
6
28
9
52
11
22
13
7
20
7
7
486
724
256
124
134
10
7
26
20
127
20
20
48
11
6
51
11
109
15
38
19
8
34
8
8
transposition, DNA-mediated
DNA integration
translation
G-protein coupled receptor signaling pathway
DNA repair
positive regulation of cell differentiation
mitochondrial respiratory chain complex IV assembly
endocrine pancreas development
transcription initiation from RNA polymerase II promoter
protein glycosylation
transcription from RNA polymerase III promoter
pseudouridine synthesis
neuropeptide signalling pathway
response to radiation
adult feeding behavior
rRNA processing
iron ion transport
regulation of cell cycle
regulation of cell death
response to oxidative stress
activation of cysteine-type endopeptidase activity involved in apoptotic process
response to cAMP
cytoplasmic translation
lipid storage
protein repair
a) Down regulated
GO:0006313
GO:0015074
GO:0006412
GO:0007186
GO:0006281
GO:0045597
GO:0033617
GO:0031018
GO:0006367
GO:0006486
GO:0006383
GO:0001522
GO:0007218
GO:0009314
GO:0008343
GO:0006364
GO:0006826
GO:0051726
GO:0010941
GO:0006979
GO:0006919
GO:0051591
GO:0002181
GO:0019915
GO:0030091
b) Up regulated
GO:0007156
GO:0007155
GO:0007165
GO:0043087
GO:0007010
GO:0035023
GO:0008360
GO:0001755
GO:1902287
GO:0007416
GO:0030334
GO:0090129
GO:0007016
GO:0007162
GO:0045879
GO:0007411
GO:0007018
GO:0007219
GO:0050772
GO:0048843
GO:0046777
GO:0018105
GO:0050919
GO:0071526
4.13E-30
4.93E-13
3.96E-12
9.72E-11
5.59E-09
6.43E-09
8.13E-09
1.28E-08
8.40E-08
1.70E-06
2.47E-06
2.55E-06
2.95E-06
5.26E-06
5.42E-06
6.17E-06
8.45E-06
1.41E-05
1.43E-05
2.83E-05
3.93E-05
5.24E-05
5.33E-05
5.33E-05
206
164
371
40
76
116
60
68
25
30
46
19
22
14
17
56
93
43
13
30
45
39
29
29
306
294
794
50
126
211
93
109
30
42
74
23
28
15
20
98
178
71
14
45
79
66
44
44
homophilic cell adhesion via plasma membrane adhesion molecules
cell adhesion
signal transduction
regulation of GTPase activity
cytoskeleton organization
regulation of Rho protein signal transduction
regulation of cell shape
neural crest cell migration
semaphorin-plexin signaling pathway involved in axon guidance
synapse assembly
regulation of cell migration
positive regulation of synapse maturation
cytoskeletal anchoring at plasma membrane
negative regulation of cell adhesion
negative regulation of smoothened signaling pathway
axon guidance
microtubule-based movement
Notch signaling pathway
positive regulation of axonogenesis
negative regulation of axon extension involved in axon guidance
protein autophosphorylation
peptidyl-serine phosphorylation
negative chemotaxis
semaphorin-plexin signaling pathway
GO:0007268
5.42E-05
97
200
synaptic transmission
GO terms ranked according to p-value. In DE = number of number of down- or up-regulated genes (q<0.15); In All = total number of
genes carrying the term.
116
117
16
118
119
120
Table S4 Top 25 GO-terms enriching the down- or up-regulated genes in EE2-treated females
at first feeding (see Fig. S3f).
GO
identifier
p-value
In DE
In ALL
Biological process
1.15E-09
6.02E-08
5.08E-06
7.07E-06
8.50E-06
1.05E-05
1.29E-05
3.55E-05
5.56E-05
5.78E-05
6.72E-05
6.81E-05
7.42E-05
9.28E-05
9.45E-05
1.80E-04
1.83E-04
1.85E-04
1.91E-04
2.06E-04
2.27E-04
2.99E-04
4.02E-04
4.58E-04
5.12E-04
35
48
10
22
16
29
21
15
150
7
10
34
52
22
14
55
264
41
10
8
56
15
9
16
16
76
135
14
50
31
76
46
32
644
9
16
99
188
59
29
198
1276
140
17
12
215
37
15
36
41
membrane depolarization during action potential
protein deubiquitination
positive regulation of axon extension
regulation of GTPase activity
neuronal action potential
protein ubiquitination involved in ubiquitin-dependent protein catabolic process
regulation of small GTPase mediated signal transduction
sensory perception of pain
intracellular signal transduction
mechanosensory behavior
endosome organization
transmembrane receptor protein tyrosine kinase signalling pathway
ubiquitin-dependent protein catabolic process
calcium ion import
swimming behaviour
heart development
regulation of transcription, DNA-templated
mRNA processing
negative regulation of ERK1 and ERK2 cascade
olfactory bulb development
chordate embryonic development
regulation of actin cytoskeleton organization
larval locomotory behavior
smoothened signaling pathway
RNA secondary structure unwinding
a) Down regulated
GO:0086010
GO:0016579
GO:0045773
GO:0043087
GO:0019228
GO:0042787
GO:0051056
GO:0019233
GO:0035556
GO:0007638
GO:0007032
GO:0007169
GO:0006511
GO:0070509
GO:0036269
GO:0007507
GO:0006355
GO:0006397
GO:0070373
GO:0021772
GO:0043009
GO:0032956
GO:0008345
GO:0007224
GO:0010501
b) Up regulated
GO:0006412
GO:0006457
GO:0006260
GO:0007017
GO:0006281
GO:0051301
GO:0000413
GO:0010499
GO:0015986
GO:0051258
GO:0061077
GO:0030150
GO:0007076
GO:0000398
GO:0006488
GO:0006313
GO:0007586
GO:0019882
GO:0000278
GO:0000103
GO:0006122
GO:0033617
GO:0002479
9.88E-25
6.10E-08
1.79E-07
3.06E-07
8.23E-07
3.20E-06
3.91E-06
1.79E-05
4.94E-05
6.03E-05
1.68E-04
1.82E-04
1.91E-04
3.06E-04
3.27E-04
4.49E-04
8.68E-04
8.72E-04
9.14E-04
9.38E-04
9.66E-04
1.10E-03
1.16E-03
138
69
43
45
57
55
20
20
23
33
11
14
8
39
7
151
5
5
12
7
11
6
7
256
160
88
92
134
130
32
34
44
72
16
23
10
99
8
486
5
5
21
9
18
7
9
GO:0010950
1.16E-03
7
9
translation
protein folding
DNA replication
microtubule-based process
DNA repair
cell division
protein peptidyl-prolyl isomerization
proteasomal ubiquitin-independent protein catabolic process
ATP synthesis coupled proton transport
protein polymerization
chaperone-mediated protein folding
protein import into mitochondrial matrix
mitotic chromosome condensation
mRNA splicing, via spliceosome
dolichol-linked oligosaccharide biosynthetic process
transposition, DNA-mediated
digestion
antigen processing and presentation
mitotic cell cycle
sulfate assimilation
mitochondrial electron transport, ubiquinol to cytochrome c
mitochondrial respiratory chain complex IV assembly
antigen processing and presentation of exogenous peptide antigen via MHC class I,
TAP-dependent
positive regulation of endopeptidase activity
GO:2000045
1.16E-03
7
9
regulation of G1/S transition of mitotic cell cycle
GO terms ranked according to p-value. In DE = number of down- or up-regulated genes (q<0.15); In All = total number of genes
carrying the term.
121
122
17
123
124
125
Table S5 Top 25 GO-terms enriching the down- or up-regulated genes in EE2-treated males
and females at hatching.
GO
identifier
p-value
In DE
In ALL
Biological process
GO:0006556
GO:0043535
GO:0003056
GO:0046541
GO:0002504
0.000571116
0.003013204
0.006168328
0.006168328
0.00621144
2
1
1
1
1
12
1
2
2
2
GO:0042843
GO:0046785
GO:0030299
GO:0000707
GO:0007197
0.008960946
0.008999982
0.009162242
0.009202101
0.009274174
1
1
1
1
1
3
3
3
3
3
GO:0007207
0.009274174
1
3
GO:0006730
GO:1990697
GO:0003262
GO:0006312
GO:0042148
GO:0045987
GO:0007626
0.010359431
0.012068608
0.014704077
0.015110164
0.015110164
0.01533806
0.017394418
2
1
1
1
1
1
2
52
4
5
5
5
5
68
S-adenosylmethionine biosynthetic process
regulation of blood vessel endothelial cell migration
regulation of vascular smooth muscle contraction
saliva secretion
antigen processing and presentation of peptide or polysaccharide antigen via MHC
class II
D-xylose catabolic process
microtubule polymerization
intestinal cholesterol absorption
meiotic DNA recombinase assembly
adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signalling
pathway
phospholipase C-activating G-protein coupled acetylcholine receptor signalling
pathway
one-carbon metabolic process
protein depalmitoleylation
endocardial progenitor cell migration to the midline involved in heart field formation
mitotic recombination
strand invasion
positive regulation of smooth muscle contraction
locomotory behavior
GO:0006166
GO:0019370
GO:0046330
GO:0033198
GO:0006082
GO:0007131
GO:0015015
0.021278412
0.023528896
0.023809516
0.027397657
0.029774206
0.030031765
0.032060673
1
1
1
1
1
1
1
7
8
8
9
10
10
11
purine ribonucleoside salvage
leukotriene biosynthetic process
positive regulation of JNK cascade
response to ATP
organic acid metabolic process
reciprocal meiotic recombination
heparan sulfate proteoglycan biosynthetic process, enzymatic modification
a) Down regulated
b) Up regulated
GO:0045899
2.24E-07
4
12
GO:1901800
GO:0030433
GO:1902254
GO:0009190
GO:0019226
GO:2000311
2.24E-07
1.31E-06
6.54E-04
7.87E-04
2.00E-03
2.00E-03
4
5
2
2
2
2
12
41
9
10
16
16
GO:0035907
GO:0030163
GO:0000723
GO:0035493
GO:0000012
GO:0060042
GO:0042593
GO:0070266
GO:1990108
GO:2001242
GO:0006507
GO:0016254
GO:0001878
GO:0010569
GO:0006420
GO:0070306
GO:0042092
2.50E-03
3.05E-03
3.50E-03
3.74E-03
7.48E-03
1.13E-02
1.13E-02
1.21E-02
1.21E-02
1.21E-02
1.27E-02
1.35E-02
1.42E-02
1.47E-02
1.49E-02
1.50E-02
1.57E-02
2
2
2
1
1
2
1
1
1
1
1
1
2
1
1
1
1
17
18
22
1
2
38
3
3
3
3
3
3
40
4
4
4
4
positive regulation of RNA polymerase II transcriptional preinitiation complex
assembly
positive regulation of proteasomal protein catabolic process
ER-associated ubiquitin-dependent protein catabolic process
negative regulation of intrinsic apoptotic signalling pathway by p53 class mediator
cyclic nucleotide biosynthetic process
transmission of nerve impulse
regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective
glutamate receptor activity
dorsal aorta development
protein catabolic process
telomere maintenance
SNARE complex assembly
single strand break repair
retina morphogenesis in camera-type eye
glucose homeostasis
necroptotic process
protein linear deubiquitination
regulation of intrinsic apoptotic signalling pathway
GPI anchor release
preassembly of GPI anchor in ER membrane
response to yeast
regulation of double-strand break repair via homologous recombination
arginyl-tRNA aminoacylation
lens fiber cell differentiation
type 2 immune response
GO:0015904
1.63E-02
1
3
tetracycline transport
GO terms ranked according to p-value. In DE = number of down- or up-regulated genes (q<0.15); In All = total number of genes
carrying the term.
126
127
18