Versions 2

Table of Contents

Namespaces

Unused Namespaces 4

The source BEL script contained references to the following namespaces, but they were never used. It is suggested to delete their definitions from the BEL script to improve readability and parsing speed.

  • GOBP
  • MESHD
  • MESHPP
  • MGI

Annotations

This section lists all of the annotations that are defined in the original BEL script.

Keyword URL Stratify
CellLine https://arty.scai.fraunhofer.de/artifactory/bel/annotation/cell-line/cell-line-20170511.belanno View Stratified Summary
MeSHAnatomy https://arty.scai.fraunhofer.de/artifactory/bel/annotation/mesh-anatomy/mesh-anatomy-20170511.belanno View Stratified Summary
MeSHDisease https://arty.scai.fraunhofer.de/artifactory/bel/annotation/mesh-diseases/mesh-diseases-20170725.belanno View Stratified Summary
Species https://arty.scai.fraunhofer.de/artifactory/bel/annotation/species-taxonomy-id/species-taxonomy-id-20170511.belanno View Stratified Summary

Unused Annotations 7

The source BEL script contained references to the following annotations, but they were never used. It is suggested to delete their definitions from the BEL script to improve readability and parsing speed.

Note: this may be due to errors occurring in all statements with these annotations.

  • Assay
  • CellLine
  • Dosage
  • MeSHAnatomy
  • MeSHDisease
  • Section
  • Species

Locally Defined Annotations 3

The source BEL script contained annotations defined as a list. Click each link to export the list definition as a BELANNO file that can hosted externally to promote re-usability and interoperability. After, you can replace the list definition in the source BEL with a SET ANNOTATION X AS URL "Y" definition.

Unused Locally Defined Annotations 3

The source BEL script contained the following list annotations, but no references to the following values. It is suggested to prune these values from the list definitions.

Note: this may be due to errors occurring in all statements with these annotations.

Annotation Values
Assay
  • Cytotoxicity assay
  • orthogonal sedimentation assay
  • thioflavine-T (ThT) binding and fluorescence assay
  • MT-polymerization assay
Dosage
  • 100microM
  • 5mg/kg
Section
  • Discussion
  • Conclusion
  • Abstract
  • Pharmacokinetic Studies
  • Compound Evaluation in Vitro

Warning Statistics

All Parser Warnings 78

A faceted table view of all parser warnings can be viewed and exported from here.

Line BEL Message
38 SET Support= "Agents capable of preventing the misfolding and sequestration of the microtubule-stabilizing protein tau into insoluble fibrillar aggregates hold considerable promise for the prevention and/or treatment of neurodegenerative tauopathies such as Alzheimer's disease" "Support" is not defined
43 SET Species = "Mus musculus" "Mus musculus" is not defined in the Species annotation
44 SET MESHD="Alzheimer Disease" "MESHD" is not defined
46 p(MGI:Mapt)--path(MESHD:Taupathies) "Taupathies" is not in the MESHD namespace
47 p(MGI:Mapt)--path(MESHD:Amyloidosis) Missing evidence; can't add: p(MGI:Mapt)--path(MESHD:Amyloidosis)
48 p(MGI:Mapt)--path(MESHD:"Alzheimer Disease") Missing evidence; can't add: p(MGI:Mapt)--path(MESHD:"Alzheimer Disease")
50 SET Support= "Recently, we reported the discovery of the aminothienopyridazine (ATPZ) class of tau aggregation inhibitors and now describe a series of new analogues that are both effective inhibitors of tau fibrillization and display significant brain-to-plasma exposure ratios after administration to mice" "Support" is not defined
55 SET Species = "Mus musculus" "Mus musculus" is not defined in the Species annotation
56 SET MESHD ="Alzheimer Disease" "MESHD" is not defined
58 a(aminothienopyridazine) -| bp(GOBP:"neurofibrillary tangle assembly") [pos:2] "aminothienopyridazine" should be qualified with a valid namespace
59 a(aminothienopyridazine)--path(MESHD:Tauopathies) [pos:2] "aminothienopyridazine" should be qualified with a valid namespace
61 SET Support=" Further, two of the most promising examples, 15 and 16, were found to reach significant brain exposure levels following oral administration" "Support" is not defined
64 SET Species = "Mus musculus" "Mus musculus" is not defined in the Species annotation
65 SET MESHD="Alzheimer Disease" "MESHD" is not defined
66 a("5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")->bp(MESHPP:Pharmacokinetics) [pos:2] "5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
67 a("5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide") ->bp(MESHPP:Pharmacokinetics) [pos:2] "5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
69 SET Support=" Taken together, these results suggest that examples from the ATPZ class hold promise as candidates for in vivo efficacy studies in animal models of neurodegenerative tauopathies" "Support" is not defined
72 SET Species = "Mus musculus" "Mus musculus" is not defined in the Species annotation
73 SET MESHD ="Alzheimer Disease" "MESHD" is not defined
74 a("5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")--path(MESHD:Tauopathies) [pos:2] "5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
75 a("5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")--path(MESHD:Tauopathies) [pos:2] "5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
78 SET Support= "The ATPZs exhibited IC50 values in the 2-32 microM range in the primary ThT assay, with maximal percent inhibition of 70-85%" "Support" is not defined
82 SET CellLine = "HEK-293 cells" "HEK-293 cells" is not defined in the CellLine annotation
83 SET MESHD="Alzheimer Disease" "MESHD" is not defined
85 SET Dosage = "2-32 microM" "2-32 microM" is not defined in the Dosage annotation
87 a(aminothienopyridazine)-| bp(GOBP:"neurofibrillary tangle assembly") [pos:2] "aminothienopyridazine" should be qualified with a valid namespace
89 SET Support= "The activity against tau fibrillization was confirmed by sedimentation assay, where the majority of compounds exhibited>50%reduction in pelletable material compared to the untreated control" "Support" is not defined
93 SET CellLine = "HEK-293 cells" "HEK-293 cells" is not defined in the CellLine annotation
94 SET MESHD= "Alzheimer Disease" "MESHD" is not defined
96 SET Assay= " orthogonal sedimentation assay" " orthogonal sedimentation assay" is not defined in the Assay annotation
97 a(aminothienopyridazine) -| act(bp(GOBP:"neurofibrillary tangle assembly")) [pos:2] "aminothienopyridazine" should be qualified with a valid namespace
99 SET Support= "Also consistent with our previous studies is the observation that all ATPZs tested (i.e., 8, 10, 11, 13-19) did not appear to interfere with the normal MT-stabilizing function of tau in a MT-polymerization assay" "Support" is not defined
103 SET CellLine = "HEK-293 cells" "HEK-293 cells" is not defined in the CellLine annotation
104 SET MESHD ="Alzheimer Disease" "MESHD" is not defined
105 SET Assay=" MT-polymerization assay " " MT-polymerization assay " is not defined in the Assay annotation
107 a(aminothienopyridazine) -| bp(GOBP:"neurofibrillary tangle assembly") [pos:2] "aminothienopyridazine" should be qualified with a valid namespace
110 SET Support = "Finally,to evaluate possible major toxicities associated with the ATPZs, all test compounds were evaluated in a cytotoxicity assay that employs rapidly dividing HEK-293 cells. All compounds were found to be nontoxic at 100 microM." "Support" is not defined
114 SET MESHD ="Alzheimer Disease" "MESHD" is not defined
115 SET CellLine = "HEK-293 cells" "HEK-293 cells" is not defined in the CellLine annotation
118 a(aminothienopyridazine)causesNoChange bp(MESHPP:"Cytotoxicity, Immunologic") [pos:2] "aminothienopyridazine" should be qualified with a valid namespace
122 SET Support = " Finally, among the amide derivatives, 14, 15and 16 appeared to be particularly interesting because of favorable B/P ratios combined with promising indications of good metabolic stability" "Support" is not defined
128 SET Species = "Mus musculus" "Mus musculus" is not defined in the Species annotation
129 SET MESHD ="Alzheimer Disease" "MESHD" is not defined
130 SET Dosage = "5 mg/kg" "5 mg/kg" is not defined in the Dosage annotation
132 a("5-Amino-3-(4-chlorophenyl)-N-ethyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")->bp(MESHPP:Pharmacokinetics) [pos:2] "5-Amino-3-(4-chlorophenyl)-N-ethyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
133 a("5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")->bp(MESHPP:Pharmacokinetics) [pos:2] "5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
134 a("5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide") ->bp(MESHPP:Pharmacokinetics) [pos:2] "5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
136 SET Support = "Furthermore, these data reveal that 16 exhibits good metabolic stability as indicated by an elimination half-life of >= 2.5h in plasma. " "Support" is not defined
139 SET Species = "Mus musculus" "Mus musculus" is not defined in the Species annotation
140 SET MESHD ="Alzheimer Disease" "MESHD" is not defined
141 SET Dosage = "5 mg/kg" "5 mg/kg" is not defined in the Dosage annotation
142 a("5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide") ->bp(MESHPP:Pharmacokinetics) [pos:2] "5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
145 SET Support="Comparison of the integrated area under the curve(AUC)in plasma after oral and iv administration of 16 revealed an oral bioavailability(F)of 70% (cf., Figure 6A and Figure 6B)." "Support" is not defined
148 SET Species = "Mus musculus" "Mus musculus" is not defined in the Species annotation
149 SET MESHD = "Alzheimer Disease" "MESHD" is not defined
150 a("5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")-> bp(MESHPP:"Biological Availability") [pos:2] "5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
153 SET Support=" Results from the invitro efficacy studies appeared to be fully consistent with our previous results and confirmed that the the ATPZs are most effective in preventing tau fibrillization when present in 1:1molar ratio with tau (i.e., 15 microM in the fibrillization assay" "Support" is not defined
158 SET MESHD ="Alzheimer Disease" "MESHD" is not defined
159 SET CellLine = "HEK-293 cells" "HEK-293 cells" is not defined in the CellLine annotation
160 a(aminothienopyridazine)-|bp(GOBP:"neurofibrillary tangle assembly") [pos:2] "aminothienopyridazine" should be qualified with a valid namespace
162 SET Support="Furthermore,selectedamidederivatives,suchas14,15, and 16, were found to reach brain concentrations above 800 ng/g (i.e., >2 microM) 1 h after ip administration of 5 mg/kg" "Support" is not defined
166 SET MESHD ="Alzheimer Disease" "MESHD" is not defined
167 SET Species = "Mus musculus" "Mus musculus" is not defined in the Species annotation
169 a("5-Amino-3-(4-chlorophenyl)-N-ethyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")--bp(GOBP:"negative regulation of maintenance of permeability of blood-brain barrier") [pos:2] "5-Amino-3-(4-chlorophenyl)-N-ethyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
170 a("5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")--bp(GOBP:"negative regulation of maintenance of permeability of blood-brain barrier") [pos:2] "5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
171 a("5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")--bp(GOBP:"negative regulation of maintenance of permeability of blood-brain barrier") [pos:2] "5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
173 SET Support= "Equally important, significant brain concentrations were also observed after oral administration of 15 or 16, with the oral bioavailability of the latter compound being ~70%. " "Support" is not defined
176 SET MESHD ="Alzheimer Disease" "MESHD" is not defined
177 SET Species = "Mus musculus" "Mus musculus" is not defined in the Species annotation
179 a("5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")-> bp(MESHPP:"Biological Availability") [pos:2] "5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
180 a("5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")-> bp(MESHPP:"Biological Availability") [pos:2] "5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
182 SET Support ="To this end, the ATPZs presented here appear to be very promising candidates because of a favorable combination of biological activity in vitro and desirable PK properties, including excellent brain penetration and oral bioavailability" "Support" is not defined
187 SET MESHD ="Alzheimer Disease" "MESHD" is not defined
188 SET CellLine = "HEK-293 cells" "HEK-293 cells" is not defined in the CellLine annotation
189 a("5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")->bp(MESHPP:"Biological Availability") [pos:2] "5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
190 a("5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")->bp(MESHPP:"Biological Availability") [pos:2] "5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
191 a("5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")--bp(GOBP:"negative regulation of maintenance of permeability of blood-brain barrier") [pos:2] "5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace
192 a("5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide")--bp(GOBP:"negative regulation of maintenance of permeability of blood-brain barrier") [pos:2] "5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace

Top Warnings

Error Frequency
"Support" is not defined 15
"MESHD" is not defined 15
"Mus musculus" is not defined in the Species annotation 9
[pos:2] "5-Amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace 9
[pos:2] "aminothienopyridazine" should be qualified with a valid namespace 7
[pos:2] "5-Amino-3-(4-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace 7
"HEK-293 cells" is not defined in the CellLine annotation 6
"5 mg/kg" is not defined in the Dosage annotation 2
[pos:2] "5-Amino-3-(4-chlorophenyl)-N-ethyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide" should be qualified with a valid namespace 2

Naked Names 4

Names referenced without a namespace are antithetical to reproducible science and data integration practices. The list of "naked names" can be downloaded here for further use with tools to help find the appropriate names.

Namespaces with Incorrect Names 1

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of the open source project, PyBEL. Please feel free to contact us here to give us feedback or report any issues.