Difference between revisions of "Molecule"
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[[Example molecule pages]]<br> | [[Example molecule pages]]<br> | ||
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| + | ==Molecule Curation== | ||
| + | Molecule curation will capture chemical and drug entities that have been shown to affect the biology of the worm, as well as allow users to link to other databases that deal with these molecule entities in greater detail. | ||
| + | |||
| + | * What we mean by small molecule | ||
| + | ** drug | ||
| + | ** metabolite (primary and secondary) | ||
| + | ** monomers or very small oligomers of nucleic acids, proteins, and polysaccharides | ||
| + | ** "Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions." (from [http://www.nlm.nih.gov/cgi/mesh/2009/MB_cgi?mode=&index=24714&field=all&HM=&II=&PA=&form=&input= nlm.nih.gov] and [http://en.wikipedia.org/wiki/Small_molecule wikipedia]) | ||
| + | |||
==Approved model== | ==Approved model== | ||
| − | |||
| − | |||
///////////////////////////small molecule/chemical/drug //////////////////////////// | ///////////////////////////small molecule/chemical/drug //////////////////////////// | ||
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* DB_info -> links to entity in other database add following databases to database.ace | * DB_info -> links to entity in other database add following databases to database.ace | ||
| − | + | ==Molecule curation== | |
| − | == | ||
| − | Molecule curation | ||
| − | |||
| − | |||
| − | |||
| − | |||
| − | |||
| − | |||
===Drug-phenotype curation=== | ===Drug-phenotype curation=== | ||
| Line 58: | Line 57: | ||
Molecules will also be linked to genes through their influence on gene activity directly through gene regulation interactions. | Molecules will also be linked to genes through their influence on gene activity directly through gene regulation interactions. | ||
| − | ==Molecule databases== | + | ===Molecule databases=== |
Molecule IDs will be provided, when available, for the following databases:<br> | Molecule IDs will be provided, when available, for the following databases:<br> | ||
*Database "NLM_MeSH" "UID" | *Database "NLM_MeSH" "UID" | ||
| Line 66: | Line 65: | ||
*Database "KEGG COMPOUND" "ACCESSION_NUMBER" | *Database "KEGG COMPOUND" "ACCESSION_NUMBER" | ||
| − | ==Molecule list== | + | ===Molecule list=== |
Initially, we will be using MeSH UIDs, assigned by the NLM, as IDs for the molecules in our database. Due to the more comprehensive coverage of the NLM molecules, and the fact that it is more stably funded, this source was thought to be a good starting point for this project. The list we are starting with is a pared down list of molecules from the NLM, that was created by the Comparative Toxicogenomic Database (CTD), which contains over 130,000 terms. For each term, this list contains a term name, CTD ID, MeSH UID, and where available CAS Registry Numbers. Using the CasRNs, we extracted the ChEBI ID from the Chemical Entities of Biological Interest database entity list, where it existed, along with any KEGG Compound accession number. | Initially, we will be using MeSH UIDs, assigned by the NLM, as IDs for the molecules in our database. Due to the more comprehensive coverage of the NLM molecules, and the fact that it is more stably funded, this source was thought to be a good starting point for this project. The list we are starting with is a pared down list of molecules from the NLM, that was created by the Comparative Toxicogenomic Database (CTD), which contains over 130,000 terms. For each term, this list contains a term name, CTD ID, MeSH UID, and where available CAS Registry Numbers. Using the CasRNs, we extracted the ChEBI ID from the Chemical Entities of Biological Interest database entity list, where it existed, along with any KEGG Compound accession number. | ||
| − | A sample molecule | + | A sample molecule.ace record: |
Molecule : "C009687" | Molecule : "C009687" | ||
Public_name "wortmannin" | Public_name "wortmannin" | ||
| Line 88: | Line 87: | ||
*We do not have definitions of the terms, nor are the terms arranged in any hierarchical manner; however other databases do, and we provide links to those websites if an ID is available. | *We do not have definitions of the terms, nor are the terms arranged in any hierarchical manner; however other databases do, and we provide links to those websites if an ID is available. | ||
*Terms and synonyms of terms, will be added as needed, this curation effort still needs to be worked out, ideally the list will be incorporated as a selection list for whatever curation tool a curator is using. | *Terms and synonyms of terms, will be added as needed, this curation effort still needs to be worked out, ideally the list will be incorporated as a selection list for whatever curation tool a curator is using. | ||
| − | |||
==Molecule Curation Pipeline== | ==Molecule Curation Pipeline== | ||
Before each upload the molecule.ace file must be made. This file will need to contain all the molecule references with in the RNAi, and Variation Phenotype curation and merge them with the molecule data from the molecule list. | Before each upload the molecule.ace file must be made. This file will need to contain all the molecule references with in the RNAi, and Variation Phenotype curation and merge them with the molecule data from the molecule list. | ||
| − | ==Papers flagged for chemical== | + | ==Papers flagged for chemical/molecule curation== |
{| {{table}} border=1 | {| {{table}} border=1 | ||
| align="center" style="background:#f0f0f0;"|'''WBPaperID''' | | align="center" style="background:#f0f0f0;"|'''WBPaperID''' | ||
Revision as of 00:10, 7 July 2010
links to relevant pages
Caltech documentation
Example molecule pages
Contents
Molecule Curation
Molecule curation will capture chemical and drug entities that have been shown to affect the biology of the worm, as well as allow users to link to other databases that deal with these molecule entities in greater detail.
- What we mean by small molecule
- drug
- metabolite (primary and secondary)
- monomers or very small oligomers of nucleic acids, proteins, and polysaccharides
- "Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions." (from nlm.nih.gov and wikipedia)
Approved model
///////////////////////////small molecule/chemical/drug ////////////////////////////
//
// ?Molecule
// * metabolites: precursors, intermediates, or end products of a metabolic pathway
// * monomeric or very small oligomeric nucleic acids (not RNAi primers), e.g. ATP, ADP, cAMP, GTP, trinucleotide repeats??
// * chemicals/drugs
// * minerals, ions, salts
//
////////////////////////////////////////////////////////////////////////////////////
?Molecule Name ?Text
Public_name ?Text
Synonym ?Text
DB_info Database ?Database ?Database_field ?Accession_number
Gene_regulation Gene_regulator ?Gene_regulation XREF Molecule_regulator
Affects_phenotype_of Variation ?Variation #Evidence
Strain ?Strain #Evidence
Transgene ?Transgene #Evidence
RNAi ?RNAi #Evidence
///////////////////////////////////////////////////////////////////////////////////
Corresponding changes in touched models
///// ?Phenotype_info Affected_by Molecule ?Molecule #Evidence /////
///// ?Gene_regulation Regulator Molecule_regulator ?Molecule XREF Gene_regulator #Boolean /////
Model elements
- Name-> MeSH UID
- Public name -> common name in elegans literature
- Synonym -> other names, how do we mine these from other DBs?
- DB_info -> links to entity in other database add following databases to database.ace
Molecule curation
Drug-phenotype curation
Molecules will be linked to genes based on their influence on gene activity altered by variation, overexpression, and RNAi-based knockdown.
Drug-gene interactions
Molecules will also be linked to genes through their influence on gene activity directly through gene regulation interactions.
Molecule databases
Molecule IDs will be provided, when available, for the following databases:
- Database "NLM_MeSH" "UID"
- Database "CTD" "ChemicalID"
- Database "ChemIDplus" using the CasRN
- Database "ChEBI" "CHEBI_ID"
- Database "KEGG COMPOUND" "ACCESSION_NUMBER"
Molecule list
Initially, we will be using MeSH UIDs, assigned by the NLM, as IDs for the molecules in our database. Due to the more comprehensive coverage of the NLM molecules, and the fact that it is more stably funded, this source was thought to be a good starting point for this project. The list we are starting with is a pared down list of molecules from the NLM, that was created by the Comparative Toxicogenomic Database (CTD), which contains over 130,000 terms. For each term, this list contains a term name, CTD ID, MeSH UID, and where available CAS Registry Numbers. Using the CasRNs, we extracted the ChEBI ID from the Chemical Entities of Biological Interest database entity list, where it existed, along with any KEGG Compound accession number.
A sample molecule.ace record:
Molecule : "C009687" Public_name "wortmannin" Database "NLM_MeSH" "UID" "C009687" Database "CTD" "ChemicalID" "C009687" Database "ChemIDplus" "19545-26-7" Database "ChEBI" "CHEBI_ID" "52289" Database "KEGG COMPOUND" "ACCESSION_NUMBER" "C15181"
To make a working list of reference molecules for the various curation efforts, we used Textpresso to scan for all terms on the list that have been published in the C. elegans corpus. The resulting list is less than 6000 terms. The terms that have been identified in the corpus are available here:
http://textpresso-dev.caltech.edu/michael/molecule-obo-analysis/By-Frequency/ This is a directory of files of terms based on the number of times the term appears in the corpus.
and here:
http://textpresso-dev.caltech.edu/michael/molecule-obo-analysis/By-Frequency/all This is a list of all terms from the previous files concatenated into one.
This last file is being used as a starting file for molecule look-up by WB curators.
Caveats and notes:
- The list is now small enough that if we wanted to load it into WB at least we know that every term has some relevance to the literature (although unverified).
- The list is small enough to be amenable to editing through ontology editors like OBOedit (even though it is not an ontology).
- We do not have definitions of the terms, nor are the terms arranged in any hierarchical manner; however other databases do, and we provide links to those websites if an ID is available.
- Terms and synonyms of terms, will be added as needed, this curation effort still needs to be worked out, ideally the list will be incorporated as a selection list for whatever curation tool a curator is using.
Molecule Curation Pipeline
Before each upload the molecule.ace file must be made. This file will need to contain all the molecule references with in the RNAi, and Variation Phenotype curation and merge them with the molecule data from the molecule list.
Papers flagged for chemical/molecule curation
| WBPaperID | Comment |
| 461 | tetramisole |
| 464 | Yes |
| 484 | Yes |
| 493 | enhanced sensitivity of flu-2 mutants to EMS |
| 536 | pharmacological analysis of cell function (spermatozoan motility) not gene function |
| 1001 | Vanadate, AMP-PNP, ATP-gamma-S. NEM, Triton X-100, Taxol, analysis on unknown motor protein |
| 1010 | |
| 1524 | forskolin, NaF, AlCl3, GTPgammaS, GppNHp, GDPbetaS, pertussis toxin, cholera toxin |
| 2029 | campthothecin, berenil, trypanocidal drug, magnesium ion on DNA relaxation, and isolated topoisomerase, no gene product mentioned |
| 2116 | |
| 3137 | sodium arsenite, mercuric choride |
| 3150 | ouabain |
| 13430 | hematin, benzimidazole, Albendazole Diethylcarbamazine Fenbendazole Hematin Imidazole Ivermectin Levamisole Mebendazole Methimazole Morantel tartrate Oxibendazole Piperazine Pyrantel tartrate Thiabendazole: only tested in vitro on H. contortus GST activity. |
| 24940 | aldicarb |
| 24950 | diacetyl |
| 25017 | fig 4 |
| 25173 | Fig 5, Fig 7. |
| 28357 | yes |
| 28562 | octopamine |
| 28879 | serotonin |
| 28900 | fig.3 |
| 29114 | yes |
| 29130 | fig.3, fig.4 |
| 30726 | isoamyl alcohol |
| 30928 | fig.2 d) Exogenous serotonin and fluoxetine suppress 100G-induced DAF- 16TGFP nuclear accumulation. |
| 31225 | yes |
| 31321 | Figure 3. High NaCl accelerates aging of C. elegans |
| 31336 | nitrogen mustard |
| 31342 | yes |
| 31419 | yes |
| 31424 | fig.7 |
| 31427 | vitamin E |
| 31428 | yes |
| 31456 | tunicamycin |
| 31464 | yes |
| 31468 | fig.3 |
| 31474 | yes |
| 31482 | FUDR |
| 31483 | mPyrazine |
| 31490 | yes |
| 31509 | yes |
| 31530 | yes |
| 31535 | yes |
| 31571 | yes |
| 31593 | yes |
| 31604 | nicotine |
| 31626 | yes |
| 31627 | yes |
| 31644 | yes |
| 31657 | yes |
| 31667 | yes |
| 31669 | ethanol |
| 31672 | yes |
| 31682 | yes |
| 31683 | yes |
| 31690 | yes |
| 31694 | yes |
| 31703 | haem |
| 31810 | yes |
| 31824 | yes |
| 31834 | yes |
| 31850 | fluorathene |
| 31857 | yes |
| 31866 | yes |
| 31871 | DHP |
| 31872 | aldicarb |
| 31873 | arsenite |
| 31882 | 8-Br-cGMP |
| 31895 | Figure 4. Responses of wild-type (N2) and slo-1 mutant worms to aldicarb and levamisole |
| 31897 | fig.4 |
| 31915 | yes |
| 31924 | yes |
| 31939 | table 2 |
| 31941 | paraquat |
| 31959 | yes |
| 31977 | imipramine |
| 31982 | glutamate |
| 31991 | Flavone (2-phenyl chromone) |
| 31992 | NaCl |
| 31994 | arsenite |
| 31996 | fig.1 |
| 31999 | diltiazem |
| 32000 | arecoline |
| 32007 | levamisole |
| 32008 | aldicarb |
| 32011 | aldicarb |
| 32031 | NaCl |
| 32033 | yes |
| 32035 | yes |
| 32050 | yes |
| 32072 | amiloride |
| 32077 | C17ISO |
| 32079 | Dextran-HCC |
| 32093 | Quercetin |
| 32101 | cadmium, chlorpyrifos, nickel, prochloraz, diuron |
| 32103 | yes |
| 32125 | imidacloprid, thiacloprid |
| 32131 | yes |
| 32142 | phosphine, FCCP (carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone), PCP (2,3,4,5,6pentachlorophenol), DNP (2,4-dinitrophenol), sodium azide |
| 32143 | yes |
| 32181 | Table S2. Activity of the ascarosides in Daf-c and Daf-d strain backgrounds in the dauer formation assay |
| 32192 | tunicamycin |
| 32207 | 1NA-PP1 |
| 32215 | butanone, benzaldehyde |
| 32232 | paraquat |
| 32237 | paraquat |
| 32241 | paraquat |
| 32243 | ceramide |
| 32252 | aldicarb |
| 32255 | H2O2 |
| 32259 | 3-methyladenine |
| 32266 | metaboilte DA dafachronic acid, steroids |
| 32271 | ethanol aldicarb |
| 32286 | root exudate |
| 32295 | Ethosuximide |
| 32319 | NaCl and isoamyl alcohol (chemoattractants). |
| 32335 | serotonin |
| 32336 | benzaldehyde |
| 32358 | aldicarb |
| 32359 | ivermectin |
| 32366 | levamisole, nicotine |
| 32390 | flavonoid quercetin |
| 32427 | volatile anesthetic, halothane |
| 32429 | 1-octanol |
| 32470 | Species specificity of dauer pheromone extracts between elegans and Pristionchus. Response of Pristionchus and Strongyloides to different dafachronic acids. |
| 32475 | mianserin methiothepin |
| 32478 | levamisole |
| 32491 | amino acids |
| 32494 | AgNO3, CdCl2,CrCl2, CoCl2, CuSO4, HgCl2, MnCl2, NiSO4, Pb(NO3)2,and ZnCl2 |
| 32508 | chlorpyrifos oxon; cadmium chloride); hexachlorophene; neurotoxicants; chlorpyrifos, methyl mercury, chlordiazepoxide, tebuconazol; Cocaine; metals, ethanol, solvents, organophosphate; carbamate pesticides |
| 32517 | Fig 1.The structures of the dauer pheromone components, ascaroside C6 (1), ascaroside C9 (2), ascaroside C3 (3), and the less active ascaroside C7 (4). Fig 2. The chemical structures of the long-chain ascarosides from conditioned medium extracts from long-term dhs-28 cultures. The structural assignment of long-chain ascaroside 17 is tentative |
| 32522 | Sulfonamide CA inhibitors (CAIs) such as acetazolamide AZA, methazolamide MZA or ethoxzolamide EZA, many new sulfonamides (such as GUZ |
| 32878 | NaN3, benzaldehyde |
| 32880 | hydrogen peroxide |
| 32881 | 5-HT; Octanol, DiD |
| 32884 | paraquat, juglone |
| 32886 | dafachronic acids; Supp. New compounds reported in this study are: III, S-III, S-V, S-XV, S-XVI, S-XXII, XXIII, S-XXIII, XXIV, XXVII. |
| 32887 | |
| 32888 | dichlorvos,an organophosphorus insecticide, acetylcholinesterase, cadmium chloride |
| 32889 | sulfonamides; CAIs; 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides possessing various 2-,3- or 4-substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, as well as the perfluorophenyl moiety; AZA and EZA |
| 32901 | CO2 |
| 32903 | paraquat |
| 32918 | Thus, (25R)-D7-dafachronic acid (2a) is one order of magnitude more active than (25R)-D4-dafachronic acid (1a). Similar to a previous study,5 little or no activity was detected with (25R)-cholestenoic acid (3a) |
| 32925 | cycloheximide |
| 32932 | resveratrol peptone |
| 32949 | Paraquat, tunicamycin |
| 32956 | These chemicals used on Pratylenchus penetrans: Acetic acid Propionic acid Isobutyric acid n-Butyric acid Isovaleric acid n-Valeric acid n-Caproic acid These chemicals used on C. elegans Acetic acid n-Caproic acid |
| 32958 | Fe-exposure |
| 32968 | tetramisole |
| 32989 | The levels of superoxide radical (.0^2-), in both mitochondria and cytosol, are increased in sod-1(tm776) and sod-1(tm783) mutants. |
| 32997 | dauer pheromone |
| 33002 | aldicarb levamisole |
| 33004 | electrically evoked and light evoked pharyngeal cholinergic post synaptic potentials reduced in amplitude by nicotinic antagonists benzoquinonium chloride and d-tubocurarine. Effect dose dependent. |
| 33009 | checked |
| 33024 | chloramine-T (CHT), DTT, H^20^2: tested for effects on both KVS-1 activity in vitro and on chemotaxis in vivo. |
| 33037 | dauer pheromone; 8-bromo-cGMP |
| 33040 | paraquat, excess O^2 |
| 33049 | Carbamate, Aldicarb, Carbofuran, Oxamyl, Neostigmine, Eserine, Organophosphates, Fenomiphos, Ethoprop, Parathion, Paraoxon, Phorate, Terbufos, meta-chlorperbenzoic acid, m-CPBA, diotioate |
| 33051 | identification of new daf-22 dependent dauer pheromone and mating pheromones ascr#7, ascr#8, and ascr#6.1 |
| 33060 | green tea polyphenol epigallocatechin gallate (EGCG) - |
| 33077 | flavopiridol olomoucine II |
| 33086 | hyperosmotic, sodium chloride, anoxia |
| 33094 | PMA induces the pnlp-29::gfp transgene |
| 33099 | dichlorvos fenamiphos organophosphates organophosphorous pesticides, neurotoxicant, mefloquine, |
| 33115 | low oxygen, lactacystn |
| 33126 | tunicamycin, glucose, deoxyglucose, sorbitol, glucose analog |
| 33130 | D-ribose affect larval growth |
| 33158 | Yes. Response to Diacetyl. |
| 33162 | The uncoupler CCCP (carbonylcyanide- 3-chlorophenylhydrazone) extends lifespan. |
| 33166 | dietary zinc |
| 33168 | Antipsychotic drugs, cyclosporin A |
| 33189 | Iron, PQS, PQS+Fe3 |
| 33433 | copper |
| 33441 | Pb, Hg, Cd, and Cr metals CdCl2, CrCl2, HgCl2, and Pb(NO3)2 in solution were used here: 2.5M, 50M, and 100M. |
| 33448 | Catechin Hydrogen peroxide catechin hydrate |
| 33456 | 8-bromo cGMP, paraquat, vinpocetine, zaprinast, EHNA (erythro-9-[2-hydroxy-3-nonyl] adenine) |
| 34686 | CdCl2, CrCl2, HgCl2, Pb(NO3)2 |
| 34687 | Screened ~54,000 chemicals from various libraries: Bioactives, natural product extracts, Analyticon purified natural product compounds, Diversity-oriented synthesis, ChemBridge kinases, ChemDiv, TimTec, MayBridge, ChemBridge. note: screened on glp-4(bn2);sek-1(km4) mutant worms Anti-infective hits that cure C. elegans of an E. faecalis infection at a concentration lower than the in vitro MIC with E. faecalis are grouped into 6 structural classes (representative structures shown). |
| 34688 | Bis-[4-methoxy-3- [3-(4-fluorophenyl)-6-(4-methylphenyl)-2(aryl)-tetrahydro-2Hpyrazolo[ 3,4-d]thiazol-5-yl]phenyl]methanes nematicidal activity |
| 34706 | Exposure to examined metals caused severe lethality toxicities in L1- and L2-larvae... |
| 34717 | fig 1, 40um juglone caused a significant increase in lifespan |
| 34757 | juglone, paraquat |
| 34758 | Rotenone, paraquat |
| 34766 | Cry5B toxin |
| 35074 | tribendimidine, levamisole, pyrantel |
| 35082 | drugs: muscimol and serotonin |
| 35083 | myxothiazol, FCCP |
| 35098 | Rib1P, 2-deoxy-a-d-ribose 1-phosphate (dRib1P), uridine, UMP, UDP, UTP, ATP, 2-deoxyuridine, 5-FU, 5dFUR, orotidine 5¢-phosphate, PPRP and 5-FU |
| 35114 | Pcm-1 mutant dauer larvae exposed to juglone develop into adults with a defect in egg-laying (Egl). Pcm-1 mutant eggs exposed to the oxidizing agents paraquat, homocysteine, and homocysteine thiolactone undergo a developmental delay more pronounced than that observed in wild-type animals. Pcm-1 mutant eggs exposed to homocysteine develop in to adults with a defect in egg-laying. |
| 35522 | 2-nonanone |
