| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T50 |
13-25 |
SP_7 |
denotes |
Severe acute |
| T51 |
26-37 |
SP_7;UBERON:0001004;GO:0045333 |
denotes |
respiratory |
| T52 |
38-60 |
SP_7 |
denotes |
syndrome coronavirus 2 |
| T53 |
62-72 |
SP_7 |
denotes |
SARS-CoV-2 |
| T54 |
105-108 |
BV_22 |
denotes |
RNA |
| T55 |
109-114 |
BV_22;NCBITaxon:10239 |
denotes |
virus |
| T56 |
145-160 |
SP_8;NCBITaxon:694002 |
denotes |
Betacoronavirus |
| T57 |
194-202 |
SP_10 |
denotes |
SARS-CoV |
| T58 |
227-231 |
SP_10 |
denotes |
SARS |
| T59 |
254-259 |
SP_6;NCBITaxon:9606 |
denotes |
human |
| T60 |
284-291 |
SO:0000704 |
denotes |
genetic |
| T61 |
317-321 |
SP_10 |
denotes |
SARS |
| T62 |
330-343 |
NCBITaxon:11118 |
denotes |
coronaviruses |
| T63 |
362-366 |
SP_2;NCBITaxon:6960 |
denotes |
bats |
| T64 |
378-385 |
SO:0000704 |
denotes |
genetic |
| T65 |
467-478 |
NCBITaxon:11118 |
denotes |
coronavirus |
| T66 |
493-501 |
SP_7 |
denotes |
COVID-19 |
| T67 |
550-558 |
SP_10 |
denotes |
SARS-CoV |
| T68 |
589-600 |
UBERON:0001004 |
denotes |
respiratory |
| T69 |
657-668 |
UBERON:0001004 |
denotes |
respiratory |
| T70 |
684-689 |
UBERON:0000062 |
denotes |
organ |
| T71 |
703-708 |
GO:0016265 |
denotes |
death |
| T72 |
775-785 |
SP_7 |
denotes |
SARS-CoV-2 |
| T73 |
816-820 |
G_3;PG_10;PR:000003622 |
denotes |
ACE2 |
| T74 |
898-905 |
G_2;PR:000016456 |
denotes |
TMPRSS2 |
| T75 |
912-919 |
MOP:0000780 |
denotes |
cleaves |
| T76 |
924-933 |
PG_1 |
denotes |
S protein |
| T77 |
945-954 |
GO:0061025 |
denotes |
fusion of |
| T78 |
955-960 |
NCBITaxon:10239;GO:0019012 |
denotes |
viral |
| T79 |
965-984 |
GO:0005765 |
denotes |
lysosomal membranes |
| T80 |
1027-1032 |
NCBITaxon:10239 |
denotes |
viral |
| T81 |
1033-1040 |
SO:0001026 |
denotes |
genomic |
| T82 |
1048-1058 |
GO:0006412 |
denotes |
translated |
| T83 |
1087-1092 |
PR:P06174 |
denotes |
ORF1a |
| T84 |
1128-1135 |
MOP:0000780 |
denotes |
cleaved |
| T85 |
1139-1144 |
NCBITaxon:10239 |
denotes |
viral |
| T86 |
1198-1203 |
NCBITaxon:10239;GO:0019012 |
denotes |
viral |
| T87 |
1204-1215 |
GO:0006260;GO:0005667 |
denotes |
replication |
| T88 |
1215-1237 |
GO:0005667 |
denotes |
/transcription complex |
| T89 |
1273-1299 |
GO:0044165 |
denotes |
host endoplasmic reticulum |
| T90 |
1309-1321 |
GO:0006900 |
denotes |
formation of |
| T91 |
1329-1337 |
GO:0016020 |
denotes |
membrane |
| T92 |
1338-1346 |
GO:0031982 |
denotes |
vesicles |
| T93 |
1361-1366 |
GO:0019012;NCBITaxon:10239 |
denotes |
viral |
| T94 |
1367-1380 |
GO:0032774 |
denotes |
RNA synthesis |
| T95 |
1393-1398 |
NCBITaxon:10239 |
denotes |
viral |
| T96 |
1403-1409 |
SO:0001026 |
denotes |
genome |
| T97 |
1413-1423 |
GO:0006260 |
denotes |
replicated |
| T98 |
1464-1471 |
SO:0001026 |
denotes |
genomic |
| T99 |
1494-1504 |
SO:0001026 |
denotes |
subgenomic |
| T100 |
1531-1541 |
GO:0006412 |
denotes |
translated |
| T101 |
1612-1617 |
NCBITaxon:10239 |
denotes |
viral |
| T102 |
1618-1625 |
SO:0001026 |
denotes |
genomes |
| T103 |
1642-1669 |
GO:0005793 |
denotes |
endoplasmic reticulum-Golgi |
| T104 |
1761-1773 |
GO:0009986 |
denotes |
cell surface |
| T105 |
1789-1799 |
GO:0006887 |
denotes |
exocytosis |
| T106 |
1845-1855 |
SP_7 |
denotes |
SARS-CoV-2 |
| T107 |
1903-1911 |
SP_10 |
denotes |
SARS-CoV |
| T108 |
1913-1923 |
SP_7 |
denotes |
SARS-CoV-2 |
| T109 |
1935-1946 |
NCBITaxon:11118 |
denotes |
coronavirus |
| T110 |
2023-2031 |
SP_10 |
denotes |
SARS-CoV |
| T111 |
2033-2043 |
SP_7 |
denotes |
SARS-CoV-2 |
| T112 |
2304-2314 |
SP_7 |
denotes |
SARS-CoV-2 |
| T113 |
2439-2447 |
SP_7 |
denotes |
COVID-19 |
| T114 |
2472-2480 |
SP_7 |
denotes |
COVID-19 |
| T115 |
2553-2563 |
DG_28 |
denotes |
remdesivir |
| T116 |
2658-2666 |
SP_7 |
denotes |
COVID-19 |
| T117 |
2677-2681 |
CHEBI:33290;CHEBI:33290 |
denotes |
Food |
| T118 |
2686-2690 |
CHEBI:23888;CHEBI:23888 |
denotes |
Drug |
| T119 |
2767-2777 |
DG_28 |
denotes |
remdesivir |
| T120 |
2808-2816 |
SP_7 |
denotes |
COVID-19 |
| T121 |
2871-2881 |
SP_7 |
denotes |
SARS-CoV-2 |
| T122 |
2894-2900 |
CHEBI:52217;CHEBI:52217 |
denotes |
agents |
| T123 |
2991-2999 |
SP_7 |
denotes |
COVID-19 |
| T124 |
3150-3155 |
NCBITaxon:10239 |
denotes |
viral |
| T125 |
3425-3434 |
GO:0065007 |
denotes |
regulates |
| T126 |
3535-3544 |
GO:0065007 |
denotes |
regulated |
| T127 |
3627-3631 |
CHEBI:23888;CHEBI:23888 |
denotes |
drug |
| T128 |
3798-3808 |
SP_7 |
denotes |
SARS-CoV-2 |
| T129 |
3928-3933 |
CHEBI:23888;CHEBI:23888 |
denotes |
drugs |
| T130 |
3938-3947 |
CHEBI:36357;CHEBI:36357 |
denotes |
compounds |
| T131 |
3976-3986 |
SP_7 |
denotes |
SARS-CoV-2 |
| T132 |
4072-4082 |
SP_7 |
denotes |
SARS-CoV-2 |
| T133 |
4110-4120 |
SP_7 |
denotes |
SARS-CoV-2 |
| T134 |
4129-4141 |
GO:0045087 |
denotes |
host-protein |
| T135 |
4142-4151 |
GO:0035556 |
denotes |
signaling |
| T136 |
4208-4212 |
CL_6 |
denotes |
Vero |
| T137 |
4256-4262 |
UBERON:0002113 |
denotes |
kidney |
| T138 |
4289-4295 |
NCBITaxon:9527 |
denotes |
monkey |
| T139 |
4297-4308 |
NCBITaxon:60711 |
denotes |
Chlorocebus |
| T140 |
4309-4316 |
NCBITaxon:9606 |
denotes |
sabaeus |
| T141 |
4406-4416 |
SP_7 |
denotes |
SARS-CoV-2 |
| T142 |
4521-4531 |
SP_7 |
denotes |
SARS-CoV-2 |
| T143 |
4818-4829 |
NCBITaxon:60711 |
denotes |
Chlorocebus |
| T144 |
4830-4837 |
NCBITaxon:9606 |
denotes |
sabaeus |
| T145 |
4842-4847 |
SP_6;NCBITaxon:9606 |
denotes |
human |
| T146 |
4884-4905 |
SO:0001811 |
denotes |
phosphorylation sites |
| T147 |
4962-4967 |
SP_6;NCBITaxon:9606 |
denotes |
human |
| T148 |
4976-4985 |
SO:0000855 |
denotes |
orthologs |
| T149 |
5266-5276 |
SP_7 |
denotes |
SARS-CoV-2 |
| T150 |
5291-5295 |
CL_6 |
denotes |
Vero |
| T151 |
5324-5334 |
SP_7 |
denotes |
SARS-CoV-2 |
| T152 |
5359-5364 |
NCBITaxon:10239 |
denotes |
viral |
| T153 |
5460-5464 |
CL_6 |
denotes |
Vero |
| T154 |
5673-5678 |
GO:0019835 |
denotes |
lysed |
| T155 |
6124-6129 |
SP_6;NCBITaxon:9606 |
denotes |
human |
| T156 |
6138-6147 |
SO:0000855 |
denotes |
orthologs |
| T157 |
6608-6618 |
SP_7 |
denotes |
SARS-CoV-2 |
| T158 |
6688-6697 |
GO:0065007 |
denotes |
regulated |
| T159 |
6840-6849 |
GO:0065007 |
denotes |
regulated |
| T160 |
6965-6969 |
SO:0000704 |
denotes |
Gene |
| T161 |
7152-7161 |
GO:0065007 |
denotes |
regulated |
| T162 |
7440-7449 |
GO:0065007 |
denotes |
regulated |
| T163 |
9912-10832 |
SP_7 |
denotes |
separated by time point and direction of phosphorylation regulation. All terms with significant over-representation (adjusted p value < 0.01) in the regulated gene set are kept, and redundant terms are removed (see STAR Methods). Numbers in cells indicate the number of genes that match the term for a given time point and direction. (G) Gene Ontology enrichment analysis for significantly phosphorylated proteins upon infection, separated by time point and direction of protein regulation. Details same as for (F).
As expected, an increase was observed in the number of significantly regulated phosphorylation sites and proteins over the infection time course, with the majority of regulation occurring at the level of phosphorylation (Figures 1E and 1F) as opposed to protein abundance (Figures 1G and 1H). Of the few proteins that significantly increased in abundance upon infection, the vast majority were SARS-CoV-2 |
| T164 |
11195-11226 |
CL_6 |
denotes |
vealed several terms related to |
| T165 |
11950-12175 |
SP_7 |
denotes |
suggesting that phosphorylation signaling represents a primary host response over this time course of infection as opposed to transcriptional regulation, which would influence protein abundance.
Phosphorylation of SARS-CoV-2 |
| T166 |
15171-15271 |
NCBITaxon:10239 |
denotes |
viruses (Figure 2E). This evolutionary pattern suggests that a negative charge in this region may pl |
| T167 |
22090-22132 |
CL_6 |
denotes |
viral entry) and were enriched in mRNA pro |
| T168 |
28170-28239 |
GO:0019835 |
denotes |
lexes, enrichment of up- or downregulated phosphorylation sites was d |
| T169 |
42510-42575 |
SP_6;NCBITaxon:9606 |
denotes |
has been described previously, and the two could be linked mechan |
| T170 |
42773-42995 |
SO:0000855 |
denotes |
or SARS-CoV-2 infection, kinase inhibitors were mapped to the most differentially regulated kinase activities (Figure 7 A) and to specific phosphorylation sites (Table S8; STAR Methods). This resulted in a list of 87 drugs |
| T171 |
50569-50590 |
SP_7 |
denotes |
shaft. The SARS-CoV-2 |
| T172 |
51285-51318 |
GO:0065007 |
denotes |
role of this kinase in regulating |
| T173 |
52719-52845 |
GO:0065007 |
denotes |
RS-CoV, Dengue virus, and influenza A virus, improving survival in mice (Fu et al., 2014; Growcott et al., 2018; Jimenez-Guard |
| T174 |
53933-53959 |
SO:0000704 |
denotes |
gulation of stress granule |
| T175 |
55801-55810 |
GO:0065007 |
denotes |
regulated |
| T176 |
58526-58597 |
GO:0065007 |
denotes |
rticles ESI SOURCE SOLUTIONS Cat#R119
Crystal Violet Solution Sigma Ald |
| T177 |
69634-69699 |
SP_6;NCBITaxon:9606 |
denotes |
http://mips.helmholtz-muenchen.de/corum/
RNA-seq dataset for tran |
| T178 |
69737-69879 |
SO:0000855 |
denotes |
o et al., 2020 GSE147507
Phosphoproteomics datasets of biological conditions Ochoa et al., 2016 https://www.embopress.org/doi/full/10.15252/ms |
| T179 |
69912-69933 |
SO:0001811 |
denotes |
phosphorylation sites |
| T180 |
69953-69992 |
SP_6;NCBITaxon:9606 |
denotes |
https://idp.nature.com/authorize?respon |
| T181 |
70001-70146 |
SO:0000855 |
denotes |
ookie&client_id=grover&redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41587-019-0344-3
Gene identifier mapping database from BioMart Ens |
| T182 |
71865-71906 |
NCBITaxon:10239 |
denotes |
https://www.bioconductor.org/packages/rel |
| T183 |
83155-83304 |
SO:0001811 |
denotes |
p control was set to All. For phosphopeptide enriched samples, data were collected using a resolving power of 30,000 and a maximum ion injection time |
| T184 |
83396-83450 |
NCBITaxon:9527 |
denotes |
maximum ion injection time of 22 ms.
Spectral library |
| T185 |
83478-83704 |
NCBITaxon:6073 |
denotes |
cessing
Raw mass spectrometry data from each DDA dataset were used to build separate libraries for DIA searches using the Pulsar search engine integrated into Spectronaut version 13.12.200217.43655 (Bruderer et al., 2015) by s |
| T186 |
83718-83754 |
NCBITaxon:9606 |
denotes |
st a database of Uniprot Chlorocebus |
| T187 |
83861-83911 |
SP_6;NCBITaxon:9606 |
denotes |
genomic sequence downloaded from GISAID (accession |
| T188 |
83974-84035 |
SO:0000704 |
denotes |
G22661T Spike V367F and G26144T ORF3a G251V) detected by RNAS |
| T189 |
86390-86413 |
NCBITaxon:10239 |
denotes |
V-2 infected Caco-2 cel |
| T190 |
86778-86784 |
CHEBI:24870;CHEBI:24870 |
denotes |
ilicon |
| T191 |
88855-88867 |
SO:0000704 |
denotes |
were transfe |
| T192 |
89485-89653 |
GO:0065007 |
denotes |
r pLVX-TetOne-Puro empty vector. 48 hours post transduction, 10 μg/mL Puromycin was added to cultures to select transduced cells. Polyclonal stable cell lines were seed |
| T193 |
90591-90639 |
GO:0065007 |
denotes |
ro E6 cells were seeded per sample. The followin |
| T194 |
91438-91498 |
GO:0065007 |
denotes |
rsus SSC-H plot. Next, typical cellular morphology was gated |
| T195 |
91503-91544 |
SO:0000704 |
denotes |
g a FSC-A versus SSC-A plot. These single |
| T196 |
92663-92694 |
SO:0000704 |
denotes |
g oligo (dT) primers and SuperS |
| T197 |
93158-93162 |
SO:0000704 |
denotes |
gene |
| T198 |
94766-94876 |
GO:0065007 |
denotes |
reater than those indicated, including a DMSO control. Plates were then transferred into the BSL-3 facility an |
| T199 |
95662-95841 |
SO:0000855 |
denotes |
ound) ∗100 and the DMSO control was then set to 100% infection for analysis. The IC50 for each experiment was determined using the Prism software (GraphPad). For select inhibitors |
| T200 |
97239-97480 |
SO:0001811 |
denotes |
pool, using Lipofectamine RNAiMAX (Thermo Fisher Scientific) according to the manufacturer’s instructions. Twenty-four (24) hours post transfection, the cell culture supernatant was removed and replaced with virus inoculum (MOI of 0.1 PFU/ce |
| T201 |
104307-104573 |
SO:0001811 |
denotes |
piens proteins
Orthologous pairs of gene identifiers between C.sabaeus and H.sapiens were downloaded from Ensembl using the BioMart web interface (http://uswest.ensembl.org/biomart/martview/6c48d59058381e6b2b198a1f91ba5e50) on April 6, 2020. Ensembl gene identifiers |
| T202 |
104809-104875 |
NCBITaxon:9527 |
denotes |
man-Wunsch global alignment algorithm implemented in the R package |
| T203 |
104900-105011 |
NCBITaxon:6073 |
denotes |
ction pairwiseAlignment with default parameters. The resulting alignments were used to convert the sequence pos |
| T204 |
105033-105059 |
NCBITaxon:9606 |
denotes |
sphorylations in C.sabaeus |
| T205 |
105146-105165 |
SP_6;NCBITaxon:9606 |
denotes |
h significant up an |
| T206 |
105210-105245 |
SO:0000704 |
denotes |
Gene Ontology (GO Biological Proces |
| T207 |
107313-107367 |
NCBITaxon:10239 |
denotes |
vities were estimated using known kinase-substrate rel |
| T208 |
108101-108104 |
CHEBI:24870;CHEBI:24870 |
denotes |
ion |
| T209 |
109969-110036 |
SO:0000704 |
denotes |
g the same Z-test based approach described for estimation of kinase |
| T210 |
110561-110799 |
GO:0065007 |
denotes |
rs of non-redundant complexes. The largest complex was selected from each cluster.
Transcription factor activity after SARS-CoV-2 infection
To evaluate the effect of SARS-CoV-2 infection at the Transcription Factor (TF) level, we applied |
| T211 |
111813-111858 |
GO:0065007 |
denotes |
response curve using the lsqcurvefit function |
