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PMC:7565482 / 11922-18589 JSONTXT

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LitCovid-PD-FMA-UBERON

Id Subject Object Predicate Lexical cue fma_id
T54 138-148 Body_part denotes nucleotide http://purl.org/sig/ont/fma/fma82740
T55 180-187 Body_part denotes genomes http://purl.org/sig/ont/fma/fma84116
T56 212-218 Body_part denotes genome http://purl.org/sig/ont/fma/fma84116
T57 219-229 Body_part denotes nucleotide http://purl.org/sig/ont/fma/fma82740
T58 396-407 Body_part denotes amino acids http://purl.org/sig/ont/fma/fma82739
T59 580-587 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T60 588-600 Body_part denotes glycoprotein http://purl.org/sig/ont/fma/fma62925
T61 974-978 Body_part denotes cell http://purl.org/sig/ont/fma/fma68646
T62 1133-1144 Body_part denotes amino acids http://purl.org/sig/ont/fma/fma82739
T63 1439-1450 Body_part denotes amino acids http://purl.org/sig/ont/fma/fma82739
T64 2105-2113 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T65 2132-2137 Body_part denotes cells http://purl.org/sig/ont/fma/fma68646
T66 2333-2339 Body_part denotes genome http://purl.org/sig/ont/fma/fma84116
T67 2455-2466 Body_part denotes amino acids http://purl.org/sig/ont/fma/fma82739
T68 2511-2517 Body_part denotes genome http://purl.org/sig/ont/fma/fma84116
T69 2607-2613 Body_part denotes Genome http://purl.org/sig/ont/fma/fma84116
T70 2823-2826 Body_part denotes HIV http://purl.org/sig/ont/fma/fma278683
T71 3018-3021 Body_part denotes HIV http://purl.org/sig/ont/fma/fma278683
T72 3074-3084 Body_part denotes amino acid http://purl.org/sig/ont/fma/fma82739
T73 3189-3193 Body_part denotes cell http://purl.org/sig/ont/fma/fma68646
T74 3212-3222 Body_part denotes Amino acid http://purl.org/sig/ont/fma/fma82739
T75 3375-3385 Body_part denotes amino acid http://purl.org/sig/ont/fma/fma82739
T76 3407-3414 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T77 3868-3878 Body_part denotes amino acid http://purl.org/sig/ont/fma/fma82739
T78 3914-3920 Body_part denotes genome http://purl.org/sig/ont/fma/fma84116
T79 3932-3943 Body_part denotes amino acids http://purl.org/sig/ont/fma/fma82739
T80 4046-4049 Body_part denotes RNA http://purl.org/sig/ont/fma/fma67095
T81 4089-4097 Body_part denotes proteins http://purl.org/sig/ont/fma/fma67257
T82 4240-4244 Body_part denotes cell http://purl.org/sig/ont/fma/fma68646
T83 4582-4589 Body_part denotes Protein http://purl.org/sig/ont/fma/fma67257
T84 4758-4765 Body_part denotes protein http://purl.org/sig/ont/fma/fma67257
T85 4940-4951 Body_part denotes amino acids http://purl.org/sig/ont/fma/fma82739
T86 5283-5287 Body_part denotes cell http://purl.org/sig/ont/fma/fma68646
T87 5362-5366 Body_part denotes cell http://purl.org/sig/ont/fma/fma68646
T88 5972-5976 Body_part denotes cell http://purl.org/sig/ont/fma/fma68646

LitCovid-PD-MONDO

Id Subject Object Predicate Lexical cue mondo_id
T40 169-177 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091
T41 863-871 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091
T42 2966-2974 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091
T43 3807-3815 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091
T44 3903-3911 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091
T45 5607-5615 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091
T46 5794-5802 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091
T47 5961-5969 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091
T48 6546-6554 Disease denotes SARS-CoV http://purl.obolibrary.org/obo/MONDO_0005091
T49 6581-6590 Disease denotes infection http://purl.obolibrary.org/obo/MONDO_0005550

LitCovid-PD-CLO

Id Subject Object Predicate Lexical cue
T95 205-206 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T96 478-480 http://purl.obolibrary.org/obo/CLO_0053733 denotes 11
T97 571-579 http://purl.obolibrary.org/obo/UBERON_0000158 denotes membrane
T98 749-757 http://purl.obolibrary.org/obo/PR_000018263 denotes Peptides
T99 796-797 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T100 828-836 http://purl.obolibrary.org/obo/PR_000018263 denotes peptides
T101 898-905 http://purl.obolibrary.org/obo/PR_000018263 denotes peptide
T102 934-941 http://purl.obolibrary.org/obo/PR_000018263 denotes peptide
T103 972-978 http://purl.obolibrary.org/obo/CL_0000084 denotes T cell
T104 1060-1068 http://purl.obolibrary.org/obo/PR_000018263 denotes peptides
T105 1130-1132 http://purl.obolibrary.org/obo/CLO_0053733 denotes 11
T106 1304-1305 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T107 1323-1331 http://purl.obolibrary.org/obo/PR_000018263 denotes peptides
T108 1371-1372 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T109 1436-1438 http://purl.obolibrary.org/obo/CLO_0053733 denotes 11
T110 1481-1491 http://purl.obolibrary.org/obo/UBERON_0000473 denotes testing is
T111 1681-1689 http://purl.obolibrary.org/obo/PR_000018263 denotes peptides
T112 1760-1768 http://purl.obolibrary.org/obo/PR_000018263 denotes peptides
T113 1770-1772 http://purl.obolibrary.org/obo/CLO_0050510 denotes 18
T114 1906-1908 http://purl.obolibrary.org/obo/CLO_0053733 denotes 11
T115 1987-1988 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T116 2067-2068 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T117 2076-2081 http://purl.obolibrary.org/obo/CLO_0009985 denotes focus
T118 2132-2137 http://purl.obolibrary.org/obo/GO_0005623 denotes cells
T119 2153-2157 http://purl.obolibrary.org/obo/UBERON_0000473 denotes test
T120 2241-2243 http://purl.obolibrary.org/obo/CLO_0050050 denotes S1
T121 2261-2263 http://purl.obolibrary.org/obo/CLO_0053733 denotes 11
T122 2296-2297 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T123 2327-2332 http://purl.obolibrary.org/obo/NCBITaxon_9606 denotes human
T124 2411-2412 http://purl.obolibrary.org/obo/CLO_0001020 denotes A
T125 2505-2510 http://purl.obolibrary.org/obo/NCBITaxon_9606 denotes human
T126 2690-2695 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes virus
T127 2757-2760 http://purl.obolibrary.org/obo/CLO_0051582 denotes has
T128 2839-2840 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T129 3187-3193 http://purl.obolibrary.org/obo/CL_0000084 denotes T cell
T130 3351-3353 http://purl.obolibrary.org/obo/CLO_0050050 denotes S1
T131 3507-3509 http://purl.obolibrary.org/obo/CLO_0053733 denotes 11
T132 4200-4201 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T133 4219-4226 http://purl.obolibrary.org/obo/PR_000018263 denotes peptide
T134 4238-4244 http://purl.obolibrary.org/obo/CL_0000084 denotes T cell
T135 4285-4290 http://purl.obolibrary.org/obo/NCBITaxon_10239 denotes virus
T136 4360-4361 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T137 4544-4546 http://purl.obolibrary.org/obo/CLO_0053733 denotes 11
T138 4663-4666 http://purl.obolibrary.org/obo/NCBITaxon_9596 denotes Pan
T139 4870-4873 http://purl.obolibrary.org/obo/NCBITaxon_9596 denotes pan
T140 4896-4897 http://purl.obolibrary.org/obo/CLO_0001020 denotes A
T141 5099-5102 http://purl.obolibrary.org/obo/NCBITaxon_9596 denotes pan
T142 5177-5182 http://purl.obolibrary.org/obo/NCBITaxon_9606 denotes human
T143 5281-5287 http://purl.obolibrary.org/obo/CL_0000084 denotes T cell
T144 5360-5366 http://purl.obolibrary.org/obo/CL_0000084 denotes T-cell
T145 5426-5434 http://purl.obolibrary.org/obo/PR_000018263 denotes peptides
T146 5783-5792 http://purl.obolibrary.org/obo/OBI_0100026 denotes organisms
T147 5783-5792 http://purl.obolibrary.org/obo/UBERON_0000468 denotes organisms
T148 5804-5806 http://purl.obolibrary.org/obo/CLO_0054055 denotes 71
T149 5808-5813 http://purl.obolibrary.org/obo/NCBITaxon_9606 denotes Human
T150 5852-5856 http://purl.obolibrary.org/obo/CLO_0053733 denotes 1: 1
T151 5881-5893 http://purl.obolibrary.org/obo/NCBITaxon_9606 denotes Homo sapiens
T152 5970-5976 http://purl.obolibrary.org/obo/CL_0000084 denotes T cell
T153 6036-6042 http://purl.obolibrary.org/obo/NCBITaxon_9606 denotes humans
T154 6187-6192 http://purl.obolibrary.org/obo/NCBITaxon_9606 denotes human
T155 6314-6322 http://purl.obolibrary.org/obo/PR_000018263 denotes peptides
T156 6459-6467 http://purl.obolibrary.org/obo/PR_000018263 denotes peptides
T157 6624-6627 http://purl.obolibrary.org/obo/NCBITaxon_9596 denotes pan
T158 6663-6665 http://purl.obolibrary.org/obo/CLO_0008922 denotes S2
T159 6663-6665 http://purl.obolibrary.org/obo/CLO_0050052 denotes S2

LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
149 63-68 Species denotes CoV-2 Tax:2697049
153 602-603 Gene denotes M Gene:43740571
154 112-117 Species denotes CoV-2 Tax:2697049
155 169-179 Species denotes SARS-CoV-2 Tax:2697049
159 863-873 Species denotes SARS-CoV-2 Tax:2697049
160 2327-2332 Species denotes human Tax:9606
161 2505-2510 Species denotes human Tax:9606
163 2541-2546 Species denotes CoV-2 Tax:2697049
166 2966-2976 Species denotes SARS-CoV-2 Tax:2697049
167 2702-2710 Disease denotes infected MESH:D007239
170 3400-3406 Gene denotes ORF1ab Gene:43740578
171 3493-3498 Species denotes CoV-2 Tax:2697049
173 3769-3774 Species denotes CoV-2 Tax:2697049
178 4027-4033 Gene denotes ORF1ab Gene:43740578
179 4076-4084 Gene denotes Helicase Gene:164045
180 3807-3817 Species denotes SARS-CoV-2 Tax:2697049
181 3903-3913 Species denotes SARS-CoV-2 Tax:2697049
184 4615-4626 Species denotes Coronavirus Tax:11118
185 4667-4678 Species denotes Coronavirus Tax:11118
206 5814-5856 Gene denotes coronavirus 229E: 1, Alphacoronavirus 1: 1
207 4790-4801 Species denotes coronavirus Tax:11118
208 4874-4885 Species denotes coronavirus Tax:11118
209 5103-5114 Species denotes coronavirus Tax:11118
210 5136-5152 Species denotes beta-coronavirus Tax:694002
211 5177-5194 Species denotes human coronavirus Tax:694448
212 5450-5455 Species denotes CoV-2 Tax:2697049
213 5607-5615 Species denotes SARS-CoV Tax:694009
214 5794-5802 Species denotes SARS-CoV Tax:694009
215 5881-5893 Species denotes Homo sapiens Tax:9606
216 5961-5969 Species denotes SARS-CoV Tax:694009
217 6036-6042 Species denotes humans Tax:9606
218 6111-6122 Species denotes coronavirus Tax:11118
219 6187-6192 Species denotes human Tax:9606
220 6255-6271 Species denotes beta-coronavirus Tax:694002
221 6422-6433 Species denotes Coronavirus Tax:11118
222 6546-6556 Species denotes SARS-CoV-2 Tax:2697049
223 6602-6615 Species denotes coronaviruses Tax:11118
224 6628-6639 Species denotes coronavirus Tax:11118
225 6581-6590 Disease denotes infection MESH:D007239

LitCovid-PD-GO-BP

Id Subject Object Predicate Lexical cue
T13 898-915 http://purl.obolibrary.org/obo/GO_0043043 denotes peptide synthesis
T14 906-915 http://purl.obolibrary.org/obo/GO_0009058 denotes synthesis
T15 4187-4196 http://purl.obolibrary.org/obo/GO_0009058 denotes synthesis
T16 6527-6542 http://purl.obolibrary.org/obo/GO_0006955 denotes immune response

LitCovid-sentences

Id Subject Object Predicate Lexical cue
T75 0-2 Sentence denotes 3.
T76 3-10 Sentence denotes Results
T77 12-16 Sentence denotes 3.1.
T78 17-91 Sentence denotes Open Reading Frames and Sequence Isolates for CoV-2-Cons Sequence Creation
T79 92-408 Sentence denotes For creation of the CoV-2 Consensus sequence, nucleotide sequences from 1731 SARS-CoV-2 genomes were aligned and a full genome nucleotide consensus was created, 23 open reading frames (ORF) were then located in the alignment using the NC_045512.2 and the Finkel et al. [46] coordinates and translated to amino acids.
T80 409-553 Sentence denotes Of the 23 ORF, 12 were canonical ORF as annotated in NC_045512.2 and 11 in alternative reading frames described by Finkel et al. [46] (Table 1).
T81 554-730 Sentence denotes In addition, the membrane protein glycoprotein (M), is completely embedded inside an extended ORF (exORFM) without any frameshifts and was not used for separate OLP set design.
T82 732-736 Sentence denotes 3.2.
T83 737-775 Sentence denotes Overlapping Peptides (OLP) Sets Design
T84 776-1051 Sentence denotes In order to achieve a balance between the number of peptides needed to cover the whole SARS-CoV-2 proteome, the costs for peptide synthesis and the design of peptide sets that allow for detecting T cell responses with high sensitivity, three OLP sets were designed (Table 2).
T85 1052-1269 Sentence denotes Shorter peptides (15 mers) with longer sequence overlap between adjacent OLP (11 amino acids) offer high resolution detection of responses, thus lowering the risk of missing longer epitopes located in the OLP overlap.
T86 1270-1389 Sentence denotes The consequence, however, will be a higher number of peptides to synthesize and screen, in this case a set of 2821 OLP.
T87 1390-1577 Sentence denotes When the overlap between OLP was reduced from 11 amino acids to 10, the sensitivity of OLP testing is maintained, but some longer epitopes located in the overlap of two OLP may be missed.
T88 1578-1741 Sentence denotes With this caveat in mind, an OLP set of 15-mers overlapping by 10 residues helped reduce the number of peptides needed by 560 OLP (total number OLP required 2262).
T89 1742-1882 Sentence denotes Similarly, longer peptides (18 mers) significantly reduce the number of OLP to be synthesized, but tend to reduce in vitro sensitivity [55].
T90 1883-1963 Sentence denotes This approach, with an 11 mer overlap, reduced the number of needed OLP to 1561.
T91 1964-2173 Sentence denotes The final decision for a specific design may also be driven by the assay system used for screening, an a-priori focus on fewer or more viral proteins and the available cells and funding to test immunogenicity.
T92 2174-2244 Sentence denotes The three full OLP sets with their entropies are included in Table S1.
T93 2245-2410 Sentence denotes Of note, the 15–11 OLP sequences were subjected to a search for homologies in the human genome to predict molecular mimicry events related to the autoimmune process.
T94 2411-2534 Sentence denotes A blastp search (>8aa consecutive identical amino acids per OLP) of the whole set against the human genome yielded no hits.
T95 2536-2540 Sentence denotes 3.3.
T96 2541-2613 Sentence denotes CoV-2-Cons Variability Analysis by Entropy Scores across the Full Genome
T97 2614-2751 Sentence denotes Mismatches between the sequence of in vitro antigen sets and the autologous virus in an infected individual can lead to missed responses.
T98 2752-2934 Sentence denotes This has been described for highly variable pathogens, such as HCV and HIV, and showed a direct relationship between sequence entropy and the frequency of detected responses [56,57].
T99 2935-3211 Sentence denotes Even though the variability of SARS-CoV-2 reported is substantially lower than for HIV and HCV, the sequence entropy was calculated at the amino acid level and as the mean OLP entropy in order to identify positions and OLP that may escape detection in T cell screening assays.
T100 3212-3395 Sentence denotes Amino acid positional Shannon entropies were generally highly conserved, although specific more variable positions were identified (Figure S1), linked to specific amino acid variants.
T101 3396-3485 Sentence denotes The ORF1ab protein, including three of the most variable positions, is shown in Figure 1.
T102 3486-3573 Sentence denotes In the CoV-2-cons 15–11 OLP set, mean OLP normalized entropies were overall low (Range:
T103 3574-3648 Sentence denotes 0.947–0.758) and comparable between OLP covering the canonical ORF (Range:
T104 3649-3717 Sentence denotes 0.947–0.879) and OLP matching the alternative frameshift ORF (Range:
T105 3718-3731 Sentence denotes 0.932–0.758).
T106 3733-3737 Sentence denotes 3.4.
T107 3738-3793 Sentence denotes Variant OLP Sequences to Cover CoV-2 Sequence Diversity
T108 3794-3996 Sentence denotes Based on the SARS-CoV-2 alignment used to design the consensus, only nine amino acid positions in the entire SARS-CoV-2 genome showed two amino acids present in at least 25% of the sequences (Figure 2).
T109 3997-4098 Sentence denotes Three of them were located in ORF1ab, one in the RNA polymerase and two in the Helicase sub-proteins.
T110 4099-4175 Sentence denotes None of them were located close enough to each other to affect the same OLP.
T111 4176-4329 Sentence denotes Still, the synthesis of a single consensus peptide could miss T cell responses in individuals exposed to the virus with the subdominant sequence variant.
T112 4330-4565 Sentence denotes To prevent missing responses, a small number of additional OLP containing each of the variants were generated to cover the variability of these OLP, creating an additional set of 31 different variant OLP in the 15–11 OLP set (Table 2).
T113 4567-4571 Sentence denotes 3.5.
T114 4572-4688 Sentence denotes Conserved Protein Sequences Matching Other Coronavirus Family Member and Identification of Pan-Coronavirus Sequences
T115 4689-4895 Sentence denotes In addition to variable positions, we also evaluated the presence of protein regions conserved among coronavirus species, as these may support the design of immunogen sequences for pan-coronavirus vaccines.
T116 4896-5057 Sentence denotes A total of 26 regions, ranging from 8 to 23 amino acids, were identified as being conserved in at least one of the three different sequence alignments (Table 3).
T117 5058-5205 Sentence denotes Fifteen fragments were identified in the pan-coronavirus alignment, 17 in the beta-coronavirus alignment and 12 in the human coronavirus alignment.
T118 5206-5258 Sentence denotes Seven of them were detected in all three alignments.
T119 5259-5475 Sentence denotes To identify potential T cell epitopes in these conserved regions, we searched the IEDB for described T-cell epitopes similar (>90% sequence identity) to the conserved peptides present in the CoV-2 consensus sequence.
T120 5476-5616 Sentence denotes Interestingly, the majority of the conserved regions contained several matches, most of which were described epitopes derived from SARS-CoV.
T121 5617-5717 Sentence denotes In total, 125 similar epitopes were identified, from all but two of the conserved regions (Table 3).
T122 5718-5803 Sentence denotes The similar epitopes were found to be derived from the following organisms; SARS-CoV:
T123 5804-5831 Sentence denotes 71, Human coronavirus 229E:
T124 5832-5854 Sentence denotes 1, Alphacoronavirus 1:
T125 5855-5873 Sentence denotes 1, Unknown origin:
T126 5874-5894 Sentence denotes 3, and Homo sapiens:
T127 5895-5898 Sentence denotes 47.
T128 5899-6147 Sentence denotes Interestingly, 24 out of 26 fragments contained the described SARS-CoV T cell epitopes, indicating that these regions are immunogenic in humans and reinforcing the idea that some degree of cross-reactivity among coronavirus can be expected [11,58].
T129 6148-6295 Sentence denotes Also, the majority, i.e., 40 of the 47 human epitopes, clustered around one single region conserved in the beta-coronavirus alignment (QGPPGTGKSH).
T130 6296-6442 Sentence denotes Several conserved peptides have thus been identified, which could potentially contain epitopes cross-reactive among different Coronavirus species.
T131 6443-6667 Sentence denotes These conserved peptides can thus provide valuable information to understand if the immune response to SARS-CoV-2 is affected by previous infection with other coronaviruses and for pan-coronavirus vaccine design (Figure S2).