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PMC:7073332 / 38201-49246 JSONTXT

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LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
452 875-883 Species denotes SARS-CoV Tax:694009
453 885-893 Species denotes MERS-CoV Tax:1335626
458 1579-1583 Species denotes HCoV Tax:694448
1087 418-421 Gene denotes ebi Gene:6907
1088 169-178 Species denotes 2019-nCoV Tax:2697049
1089 179-189 Species denotes SARS-CoV-2 Tax:2697049
1100 905-914 Species denotes HCoV-229E Tax:11137
1101 920-929 Species denotes HCoV-NL63 Tax:277944
1102 726-730 Species denotes HCoV Tax:694448
1103 817-821 Species denotes HCoV Tax:694448
1104 992-996 Species denotes HCoV Tax:694448
1105 1047-1061 Disease denotes HCoV infection MESH:D007239
1109 2228-2233 Species denotes human Tax:9606
1111 2427-2432 Species denotes human Tax:9606
1115 2494-2499 Species denotes human Tax:9606
1116 3401-3406 Species denotes human Tax:9606
1117 3654-3659 Species denotes human Tax:9606
1122 3782-3787 Species denotes human Tax:9606
1123 4758-4763 Species denotes human Tax:9606
1124 3988-3992 Species denotes HCoV Tax:694448
1125 5870-5874 Species denotes HCoV Tax:694448
1129 6507-6520 Gene denotes drugs A and B
1130 6306-6310 Species denotes HCoV Tax:694448
1131 6347-6351 Species denotes HCoV Tax:694448
1145 7949-7956 Species denotes patient Tax:9606
1146 8218-8222 Species denotes HCoV Tax:694448
1147 8580-8584 Species denotes HCoV Tax:694448
1148 9353-9357 Species denotes HCoV Tax:694448
1149 10293-10297 Species denotes HCoV Tax:694448
1150 10773-10777 Species denotes HCoV Tax:694448
1151 10962-10966 Species denotes HCoV Tax:694448
1152 11010-11014 Chemical denotes GSEA
1153 7810-7818 Disease denotes infected MESH:D007239
1154 7918-7935 Disease denotes SARS-CoV-infected MESH:C000657245
1155 8069-8081 Disease denotes CoV-infected MESH:D018352
1156 7992-7998 CellLine denotes Calu-3 CVCL:0609
1157 8082-8088 CellLine denotes Calu-3 CVCL:0609

LitCovid-PD-FMA-UBERON

Id Subject Object Predicate Lexical cue fma_id
T180 23-29 Body_part denotes Genome http://purl.org/sig/ont/fma/fma84116
T181 91-94 Body_part denotes DNA http://purl.org/sig/ont/fma/fma74412
T182 109-116 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T183 190-197 Body_part denotes genomes http://purl.org/sig/ont/fma/fma84116
T184 279-285 Body_part denotes genome http://purl.org/sig/ont/fma/fma84116
T185 300-307 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T186 597-604 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T187 736-743 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T188 838-846 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T189 949-957 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T190 997-1005 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T191 1171-1178 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T192 1232-1235 Body_part denotes RNA http://purl.org/sig/ont/fma/fma67095
T193 1335-1343 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T194 1453-1460 Body_part denotes Genomes http://purl.org/sig/ont/fma/fma84116
T195 1472-1476 Body_part denotes Gene http://purl.org/sig/ont/fma/fma74402
T196 1595-1603 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T197 2433-2440 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T198 2441-2448 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T199 2736-2743 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T200 3154-3158 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T201 3315-3319 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T202 3407-3414 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T203 3415-3422 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T204 3518-3526 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T205 3660-3667 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T206 3668-3675 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T207 4738-4742 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T208 4764-4771 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T209 5652-5656 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T210 6327-6335 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T211 7622-7626 Body_part denotes Gene http://purl.org/sig/ont/fma/fma74402
T212 7668-7672 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T213 7775-7779 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T214 7842-7846 Body_part denotes Gene http://purl.org/sig/ont/fma/fma74402
T215 8296-8300 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T216 8315-8320 Body_part denotes cells http://purl.org/sig/ont/fma/fma68646
T217 8385-8388 Body_part denotes Map http://purl.org/sig/ont/fma/fma67847
T218 8425-8429 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T219 9745-9749 Body_part denotes le s http://purl.org/sig/ont/fma/fma63048
T220 10147-10151 Body_part denotes le s http://purl.org/sig/ont/fma/fma63048
T221 10364-10368 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T222 10419-10423 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402
T223 10702-10706 Body_part denotes gene http://purl.org/sig/ont/fma/fma74402

LitCovid-PD-MONDO

Id Subject Object Predicate Lexical cue mondo_id
T157 179-187 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091
T158 875-883 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091
T159 1052-1061 Disease denotes infection http://purl.obolibrary.org/obo/MONDO_0005550
T160 1883-1886 Disease denotes BPS http://purl.obolibrary.org/obo/MONDO_0009901
T161 7918-7926 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091

LitCovid-PD-CLO

Id Subject Object Predicate Lexical cue
T271 268-270 http://purl.obolibrary.org/obo/CLO_0050050 denotes S1
T272 690-695 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes virus
T273 1273-1278 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes virus
T274 1443-1448 http://purl.obolibrary.org/obo/OGG_0000000002 denotes Genes
T275 1472-1476 http://purl.obolibrary.org/obo/OGG_0000000002 denotes Gene
T276 2228-2233 http://purl.obolibrary.org/obo/NCBITaxon_9606 denotes human
T277 2260-2261 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T278 2427-2440 http://purl.obolibrary.org/obo/PR_000029067 denotes human protein
T279 2470-2471 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T280 2494-2499 http://purl.obolibrary.org/obo/NCBITaxon_9606 denotes human
T281 2529-2530 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T282 2540-2542 http://purl.obolibrary.org/obo/CLO_0050510 denotes 18
T283 2646-2652 http://purl.obolibrary.org/obo/UBERON_0000473 denotes tested
T284 2869-2878 http://purl.obolibrary.org/obo/SO_0000418 denotes signaling
T285 3036-3038 http://purl.obolibrary.org/obo/CLO_0001547 denotes AP
T286 3039-3041 http://purl.obolibrary.org/obo/CLO_0007874 denotes MS
T287 3154-3158 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T288 3223-3228 http://purl.obolibrary.org/obo/OGG_0000000002 denotes genes
T289 3315-3319 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T290 3401-3414 http://purl.obolibrary.org/obo/PR_000029067 denotes human protein
T291 3549-3550 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T292 3654-3667 http://purl.obolibrary.org/obo/PR_000029067 denotes human protein
T293 3782-3787 http://purl.obolibrary.org/obo/NCBITaxon_9606 denotes human
T294 3955-3960 http://purl.obolibrary.org/obo/OGG_0000000002 denotes genes
T295 3977-3978 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T296 4674-4678 http://purl.obolibrary.org/obo/CLO_0009421 denotes t+∑t
T297 4674-4678 http://purl.obolibrary.org/obo/CLO_0009935 denotes t+∑t
T298 4674-4678 http://purl.obolibrary.org/obo/CLO_0052184 denotes t+∑t
T299 4674-4678 http://purl.obolibrary.org/obo/CLO_0052185 denotes t+∑t
T300 4685-4688 http://purl.obolibrary.org/obo/CL_0000990 denotes Cdc
T301 4738-4742 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T302 4758-4771 http://purl.obolibrary.org/obo/PR_000029067 denotes human protein
T303 4853-4858 http://purl.obolibrary.org/obo/UBERON_0000473 denotes tests
T304 5589-5593 http://purl.obolibrary.org/obo/UBERON_0000473 denotes test
T305 5652-5656 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T306 5784-5788 http://purl.obolibrary.org/obo/UBERON_0000473 denotes test
T307 6513-6514 http://purl.obolibrary.org/obo/CLO_0001020 denotes A
T308 6519-6520 http://purl.obolibrary.org/obo/CLO_0001021 denotes B
T309 6887-6889 http://purl.obolibrary.org/obo/CLO_0001627 denotes AA
T310 6925-6927 http://purl.obolibrary.org/obo/CLO_0001869 denotes BB
T311 7386-7387 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T312 7453-7454 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T313 7622-7626 http://purl.obolibrary.org/obo/OGG_0000000002 denotes Gene
T314 7668-7672 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T315 7775-7779 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T316 7842-7846 http://purl.obolibrary.org/obo/OGG_0000000002 denotes Gene
T317 7992-7998 http://purl.obolibrary.org/obo/CLO_0002192 denotes Calu-3
T318 8082-8088 http://purl.obolibrary.org/obo/CLO_0002192 denotes Calu-3
T319 8182-8187 http://purl.obolibrary.org/obo/OGG_0000000002 denotes genes
T320 8296-8300 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T321 8315-8320 http://purl.obolibrary.org/obo/GO_0005623 denotes cells
T322 8425-8429 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T323 8567-8569 http://purl.obolibrary.org/obo/CLO_0053755 denotes ES
T324 8933-8935 http://purl.obolibrary.org/obo/CLO_0053755 denotes ES
T325 8983-8985 http://purl.obolibrary.org/obo/CLO_0053755 denotes ES
T326 9014-9016 http://purl.obolibrary.org/obo/CLO_0053755 denotes ES
T327 9068-9070 http://purl.obolibrary.org/obo/CLO_0053755 denotes ES
T328 9099-9101 http://purl.obolibrary.org/obo/CLO_0008149 denotes ne
T329 9137-9139 http://purl.obolibrary.org/obo/CLO_0053755 denotes ES
T330 9226-9228 http://purl.obolibrary.org/obo/CLO_0053755 denotes ES
T331 9338-9343 http://purl.obolibrary.org/obo/OGG_0000000002 denotes genes
T332 9710-9711 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T333 9827-9828 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T334 10112-10113 http://purl.obolibrary.org/obo/CLO_0001021 denotes b
T335 10199-10204 http://purl.obolibrary.org/obo/CLO_0006985 denotes j - 1
T336 10199-10204 http://purl.obolibrary.org/obo/CLO_0006987 denotes j - 1
T337 10235-10236 http://purl.obolibrary.org/obo/CLO_0001021 denotes b
T338 10260-10265 http://purl.obolibrary.org/obo/CLO_0006985 denotes j = 1
T339 10260-10265 http://purl.obolibrary.org/obo/CLO_0006987 denotes j = 1
T340 10284-10289 http://purl.obolibrary.org/obo/OGG_0000000002 denotes genes
T341 10364-10368 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T342 10419-10423 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T343 10493-10498 http://purl.obolibrary.org/obo/OGG_0000000002 denotes genes
T344 10652-10657 http://purl.obolibrary.org/obo/UBERON_0000473 denotes tests
T345 10702-10706 http://purl.obolibrary.org/obo/OGG_0000000002 denotes gene
T346 10760-10765 http://purl.obolibrary.org/obo/OGG_0000000002 denotes genes
T347 10847-10849 http://purl.obolibrary.org/obo/CLO_0053755 denotes ES
T348 10918-10920 http://purl.obolibrary.org/obo/CLO_0053755 denotes ES

LitCovid-PD-CHEBI

Id Subject Object Predicate Lexical cue chebi_id
T431 91-94 Chemical denotes DNA http://purl.obolibrary.org/obo/CHEBI_16991
T432 109-116 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T433 300-307 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T434 552-556 Chemical denotes MEGA http://purl.obolibrary.org/obo/CHEBI_6617
T435 597-604 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T436 666-670 Chemical denotes MEGA http://purl.obolibrary.org/obo/CHEBI_6617
T437 736-743 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T438 838-846 Chemical denotes proteins http://purl.obolibrary.org/obo/CHEBI_36080
T439 949-957 Chemical denotes proteins http://purl.obolibrary.org/obo/CHEBI_36080
T440 997-1005 Chemical denotes proteins http://purl.obolibrary.org/obo/CHEBI_36080
T441 1171-1178 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T442 1335-1343 Chemical denotes proteins http://purl.obolibrary.org/obo/CHEBI_36080
T443 1365-1367 Chemical denotes S3 http://purl.obolibrary.org/obo/CHEBI_29388
T444 1595-1603 Chemical denotes proteins http://purl.obolibrary.org/obo/CHEBI_36080
T445 1675-1679 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T446 1714-1718 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T447 1816-1819 Chemical denotes TTD http://purl.obolibrary.org/obo/CHEBI_73659
T448 1943-1947 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T449 2004-2008 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T450 2349-2353 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T451 2433-2440 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T452 2441-2448 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T453 2736-2743 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T454 3036-3038 Chemical denotes AP http://purl.obolibrary.org/obo/CHEBI_28971|http://purl.obolibrary.org/obo/CHEBI_73393|http://purl.obolibrary.org/obo/CHEBI_81686
T457 3039-3041 Chemical denotes MS http://purl.obolibrary.org/obo/CHEBI_73613
T458 3257-3259 Chemical denotes ID http://purl.obolibrary.org/obo/CHEBI_141439
T459 3407-3414 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T460 3415-3422 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T461 3518-3526 Chemical denotes proteins http://purl.obolibrary.org/obo/CHEBI_36080
T462 3660-3667 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T463 3668-3675 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T464 3847-3852 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T465 4012-4016 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T466 4095-4099 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T467 4764-4771 Chemical denotes protein http://purl.obolibrary.org/obo/CHEBI_36080
T468 5865-5869 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T469 5996-6000 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T470 6050-6054 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T471 6150-6154 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T472 6289-6293 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T473 6327-6335 Chemical denotes proteins http://purl.obolibrary.org/obo/CHEBI_36080
T474 6337-6341 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T475 6342-6346 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T476 6389-6393 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T477 6437-6442 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T478 6507-6512 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T479 6887-6889 Chemical denotes AA http://purl.obolibrary.org/obo/CHEBI_15843|http://purl.obolibrary.org/obo/CHEBI_72816
T481 6925-6927 Chemical denotes BB http://purl.obolibrary.org/obo/CHEBI_53109
T482 7388-7392 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T483 7575-7580 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T484 8276-8281 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T485 8342-8347 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T486 8447-8452 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T487 8463-8467 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T488 8511-8515 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T489 8567-8569 Chemical denotes ES http://purl.obolibrary.org/obo/CHEBI_73509
T490 8933-8935 Chemical denotes ES http://purl.obolibrary.org/obo/CHEBI_73509
T491 8983-8985 Chemical denotes ES http://purl.obolibrary.org/obo/CHEBI_73509
T492 9014-9016 Chemical denotes ES http://purl.obolibrary.org/obo/CHEBI_73509
T493 9068-9070 Chemical denotes ES http://purl.obolibrary.org/obo/CHEBI_73509
T494 9137-9139 Chemical denotes ES http://purl.obolibrary.org/obo/CHEBI_73509
T495 9226-9228 Chemical denotes ES http://purl.obolibrary.org/obo/CHEBI_73509
T496 10385-10389 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T497 10517-10521 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T498 10847-10849 Chemical denotes ES http://purl.obolibrary.org/obo/CHEBI_73509
T499 10918-10920 Chemical denotes ES http://purl.obolibrary.org/obo/CHEBI_73509

LitCovid-PD-GO-BP

Id Subject Object Predicate Lexical cue
T60 1273-1295 http://purl.obolibrary.org/obo/GO_0019048 denotes virus–host interaction
T61 2869-2878 http://purl.obolibrary.org/obo/GO_0023052 denotes signaling
T62 3154-3169 http://purl.obolibrary.org/obo/GO_0010467 denotes gene expression
T63 7775-7790 http://purl.obolibrary.org/obo/GO_0010467 denotes gene expression
T64 7842-7857 http://purl.obolibrary.org/obo/GO_0010467 denotes Gene Expression
T65 8296-8311 http://purl.obolibrary.org/obo/GO_0010467 denotes gene expression

LitCovid-sentences

Id Subject Object Predicate Lexical cue
T234 0-21 Sentence denotes Methods and materials
T235 23-67 Sentence denotes Genome information and phylogenetic analysis
T236 68-272 Sentence denotes In total, we collected DNA sequences and protein sequences for 15 HCoVs, including three most recent 2019-nCoV/SARS-CoV-2 genomes, from the NCBI GenBank database (28 January 2020, Supplementary Table S1).
T237 273-454 Sentence denotes Whole-genome alignment and protein sequence identity calculation were performed by Multiple Sequence Alignment in EMBL-EBI database (https://www.ebi.ac.uk/) with default parameters.
T238 455-592 Sentence denotes The neighbor joining (NJ) tree was computed from the pairwise phylogenetic distance matrix using MEGA X84 with 1000 bootstrap replicates.
T239 593-675 Sentence denotes The protein alignment and phylogenetic tree of HCoVs were constructed by MEGA X84.
T240 677-712 Sentence denotes Building the virus–host interactome
T241 713-812 Sentence denotes We collected HCoV–host protein interactions from various literatures based on our sizeable efforts.
T242 813-942 Sentence denotes The HCoV-associated host proteins of several HCoVs, including SARS-CoV, MERS-CoV, IBV, MHV, HCoV-229E, and HCoV-NL63 were pooled.
T243 943-1258 Sentence denotes These proteins were either the direct targets of HCoV proteins or were involved in critical pathways of HCoV infection identified by multiple experimental sources, including high-throughput yeast-two-hybrid (Y2H) systems, viral protein pull-down assay, in vitro co-immunoprecipitation and RNA knock down experiment.
T244 1259-1369 Sentence denotes In total, the virus–host interaction network included 6 HCoVs with 119 host proteins (Supplementary Table S3).
T245 1371-1401 Sentence denotes Functional enrichment analysis
T246 1402-1604 Sentence denotes Next, we performed Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses to evaluate the biological relevance and functional pathways of the HCoV-associated proteins.
T247 1605-1660 Sentence denotes All functional analyses were performed using Enrichr85.
T248 1662-1694 Sentence denotes Building the drug–target network
T249 1695-1911 Sentence denotes Here, we collected drug–target interaction information from the DrugBank database (v4.3)86, Therapeutic Target Database (TTD)87, PharmGKB database, ChEMBL (v20)88, BindingDB89, and IUPHAR/BPS Guide to PHARMACOLOGY90.
T250 1912-1997 Sentence denotes The chemical structure of each drug with SMILES format was extracted from DrugBank86.
T251 1998-2294 Sentence denotes Here, drug–target interactions meeting the following three criteria were used: (i) binding affinities, including Ki, Kd, IC50, or EC50 each ≤10 μM; (ii) the target was marked as “reviewed” in the UniProt database91; and (iii) the human target was represented by a unique UniProt accession number.
T252 2295-2412 Sentence denotes The details for building the experimentally validated drug–target network are provided in our recent studies13,23,28.
T253 2414-2460 Sentence denotes Building the human protein–protein interactome
T254 2461-3101 Sentence denotes To build a comprehensive list of human PPIs, we assembled data from a total of 18 bioinformatics and systems biology databases with five types of experimental evidence: (i) binary PPIs tested by high-throughput yeast-two-hybrid (Y2H) systems; (ii) binary, physical PPIs from protein 3D structures; (iii) kinase-substrate interactions by literature-derived low-throughput or high-throughput experiments; (iv) signaling network by literature-derived low-throughput experiments; and (v) literature-curated PPIs identified by affinity purification followed by mass spectrometry (AP-MS), Y2H, or by literature-derived low-throughput experiments.
T255 3102-3218 Sentence denotes All inferred data, including evolutionary analysis, gene expression data, and metabolic associations, were excluded.
T256 3219-3376 Sentence denotes The genes were mapped to their Entrez ID based on the NCBI database92 as well as their official gene symbols based on GeneCards (https://www.genecards.org/).
T257 3377-3614 Sentence denotes In total, the resulting human protein–protein interactome used in this study includes 351,444 unique PPIs (edges or links) connecting 17,706 proteins (nodes), representing a 50% increase in the number of the PPIs we have used previously.
T258 3615-3736 Sentence denotes Detailed descriptions for building the human protein–protein interactome are provided in our previous studies13,23,28,93.
T259 3738-3763 Sentence denotes Network proximity measure
T260 3764-3929 Sentence denotes We posit that the human PPIs provide an unbiased, rational roadmap for repurposing drugs for potential treatment of HCoVs in which they were not originally approved.
T261 3930-4784 Sentence denotes Given C, the set of host genes associated with a specific HCoV, and T, the set of drug targets, we computed the network proximity of C with the target set T of each drug using the “closest” method:1 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\left\langle d_{CT} \right\rangle = \frac{1}{\vert\vert C \vert\vert +\vert\vert T \vert\vert}\left({\sum\limits_{c \in C}} {\min}_{t \in T}\,d\left( {c,t} \right) + {\sum\limits_{t \in T}} {\min}_{c \in C}\,d\left(c,t\right) \right),$$\end{document}dCT=1∣∣C∣∣+∣∣T∣∣∑c∈Cmint∈Tdc,t+∑t∈Tminc∈Cdc,t,where d(c, t) is the shortest distance between gene c and t in the human protein interactome.
T262 4785-5717 Sentence denotes The network proximity was converted to Z-score based on permutation tests:2 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$Z_{d_{CT}} = \frac{{d_{CT} - \overline {d_r} }}{{\sigma _r}},$$\end{document}ZdCT=dCT−dr¯σr,where \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\overline {d_r}$$\end{document}dr¯ and σr were the mean and standard deviation of the permutation test repeated 1000 times, each time with two randomly selected gene lists with similar degree distributions to those of C and T.
T263 5718-5797 Sentence denotes The corresponding P value was calculated based on the permutation test results.
T264 5798-5888 Sentence denotes Z-score < −1.5 and P < 0.05 were considered significantly proximal drug–HCoV associations.
T265 5889-5957 Sentence denotes All networks were visualized using Gephi 0.9.2 (https://gephi.org/).
T266 5959-6013 Sentence denotes Network-based rational prediction of drug combinations
T267 6014-6366 Sentence denotes For this network-based approach for drug combinations to be effective, we need to establish if the topological relationship between two drug–target modules reflects biological and pharmacological relationships, while also quantifying their network-based relationship between drug targets and HCoV-associated host proteins (drug–drug–HCoV combinations).
T268 6367-6443 Sentence denotes To identify potential drug combinations, we combined the top lists of drugs.
T269 6444-7357 Sentence denotes Then, “separation” measure SAB was calculated for each pair of drugs A and B using the following method:3 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$S_{AB} = \left\langle {d_{AB}} \right\rangle - \frac{{\left\langle {d_{AA}} \right\rangle + \left\langle {d_{BB}} \right\rangle }}{2},$$\end{document}SAB=dAB−dAA+dBB2,where \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\left\langle {d_ \cdot } \right\rangle$$\end{document}d⋅ was calculated based on the “closest” method.
T270 7358-7620 Sentence denotes Our key methodology is that a drug combination is therapeutically effective only if it follows a specific relationship to the disease module, as captured by Complementary Exposure patterns in targets’ modules of both drugs without overlapping toxic mechanisms28.
T271 7622-7650 Sentence denotes Gene set enrichment analysis
T272 7651-7736 Sentence denotes We performed the gene set enrichment analysis as an additional prioritization method.
T273 7737-7872 Sentence denotes We first collected three differential gene expression data sets of hosts infected by HCoVs from the NCBI Gene Expression Omnibus (GEO).
T274 7873-8032 Sentence denotes Among them, two transcriptome data sets were SARS-CoV-infected samples from patient’s peripheral blood94 (GSE1739) and Calu-3 cells95 (GSE33267), respectively.
T275 8033-8109 Sentence denotes One transcriptome data set was MERS-CoV-infected Calu-3 cells96 (GSE122876).
T276 8110-8188 Sentence denotes Adjusted P value less than 0.01 was defined as differentially expressed genes.
T277 8189-8282 Sentence denotes These data sets were used as HCoV–host signatures to evaluate the treatment effects of drugs.
T278 8283-8453 Sentence denotes Differential gene expression in cells treated with various drugs were retrieved from the Connectivity Map (CMAP) database36, and were used as gene profiles for the drugs.
T279 8454-9399 Sentence denotes For each drug that was in both the CMAP data set and our drug–target network, we calculated an enrichment score (ES) for each HCoV signature data set based on previously described methods97 as follows:4 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathrm {ES}} = \left\{ {\begin{array}{*{20}{c}} {{\mathrm{ES}_{\mathrm{up}}} - {\mathrm {ES}_{\mathrm{down}}},{\mathrm {sgn}}\left( {{\mathrm {ES}_{\mathrm{up}}}} \right)\, \ne \,{\mathrm {sgn}}\left( {{\mathrm {ES}_{\mathrm{down}}}} \right)} \\ {0,\mathrm {else}} \end{array}} \right.$$\end{document}ES=ESup−ESdown,sgnESup≠sgnESdown0,elseESup and ESdown were calculated separately for the up- and down-regulated genes from the HCoV signature data set using the same method.
T280 9400-10406 Sentence denotes We first computed aup/down and bup/down as5 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$a = \mathop{\max}\limits_{1 \le j \le s}\left( {\frac{j}{s} - \frac{{V\left( j \right)}}{r}} \right),$$\end{document}a=max1≤j≤sjs−Vjr,6 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$b = \mathop{\max}\limits_{1 \le j \le s}\left( {\frac{{V\left( j \right)}}{r} - \frac{{j - 1}}{s}} \right),$$\end{document}b=max1≤j≤sVjr−j−1s,where j = 1, 2, …, s were the genes of HCoV signature data set sorted in ascending order by their rank in the gene profiles of the drug being evaluated.
T281 10407-10530 Sentence denotes The rank of gene j is denoted by V(j), where 1 ≤ V(j) ≤ r, with r being the number of genes (12,849) from the drug profile.
T282 10531-10639 Sentence denotes Then, ESup/down was set to aup/down if aup/down > bup/down, and was set to −bup/down if bup/down > aup/down.
T283 10640-10857 Sentence denotes Permutation tests repeated 100 times using randomly generated gene lists with the same number of up- and down-regulated genes as the HCoV signature data set were performed to measure the significance of the ES scores.
T284 10858-11045 Sentence denotes Drugs were considered to have potential treatment effect if ES > 0 and P < 0.05, and the number of such HCoV signature data sets were used as the final GSEA score that ranges from 0 to 3.

2_test

Id Subject Object Predicate Lexical cue
32194980-29722887-19614248 558-560 29722887 denotes 84
32194980-29722887-19614249 672-674 29722887 denotes 84
32194980-27141961-19614250 1657-1659 27141961 denotes 85
32194980-24203711-19614251 1783-1785 24203711 denotes 86
32194980-26578601-19614252 1820-1822 26578601 denotes 87
32194980-21948594-19614253 1855-1857 21948594 denotes 88
32194980-17145705-19614254 1868-1870 17145705 denotes 89
32194980-24234439-19614255 1908-1910 24234439 denotes 90
32194980-24203711-19614256 1994-1996 24203711 denotes 86
32194980-14681372-19614257 2210-2212 14681372 denotes 91
32194980-30002366-19614258 2403-2405 30002366 denotes 13
32194980-31375661-19614259 2406-2408 31375661 denotes 23
32194980-30867426-19614260 2409-2411 30867426 denotes 28
32194980-26615191-19614261 3286-3288 26615191 denotes 92
32194980-30002366-19614262 3724-3726 30002366 denotes 13
32194980-31375661-19614263 3727-3729 31375661 denotes 23
32194980-30867426-19614264 3730-3732 30867426 denotes 28
32194980-31006514-19614265 3733-3735 31006514 denotes 93
32194980-30867426-19614266 7617-7619 30867426 denotes 28
32194980-15655079-19614267 7975-7977 15655079 denotes 94
32194980-23631916-19614268 8004-8006 23631916 denotes 95
32194980-30631056-19614269 8094-8096 30631056 denotes 96
32194980-17008526-19614270 8404-8406 17008526 denotes 36
32194980-21849665-19614271 8641-8643 21849665 denotes 97