Molecule

links to relevant pages
Caltech documentation
Example molecule pages

---

Overview

Molecule curation captures chemical and drug entities that have been shown to effect the biology of the worm. We provide links 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)
  • Exogenous protein complexes with toxic effects- for example - Bt toxin.

Model

Original 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 Text
           Gene_regulation Gene_regulator ?Gene_regulation XREF Molecule_regulator
           Regulate_expr_cluster ?Expression_cluster XREF Regulated_by_molecule //Wen WS228
	   WBProcess ?WBProcess XREF Molecule
           Affects_phenotype_of     Variation ?Variation ?Phenotype #Evidence
                                    Strain    ?Strain    ?Phenotype #Evidence
                                    Transgene ?Transgene ?Phenotype #Evidence
                                    RNAi      ?RNAi      ?Phenotype #Evidence
                                    Rearrangement  ?Rearrangement  ?Phenotype  #Evidence  //KY [110602 pad]
	   Interaction	?Interaction	XREF	Molecule_regulator
	   Molecule_use  ?Text  #Evidence
	   Reference ?Paper XREF Molecule
	   Remark ?Text #Evidence

Model elements

• Name-> WBMol:ID
  • originally, this field contained the MeSH ID, when no MeSH ID was available, a WBMol ID was assigned, which was supposed to be replaced by the MeSH ID when available. Unfortunately, Names are scripted to be used in URL constructions for MeSH and CTD database links resulting in WBMol_id name based URLs would have to be suppressed or, result in bad URLs. Also, the increased use of Molecule annotation in other curation pipelines resulted in confusion with object creation. These points of confusion prompted a move to change the Name field change from MeSH default IDs to WBMol IDs for all objects.
• Public name -> common name in elegans literature
• Synonym -> other names used in papers, case sensitivity. Many other names can be taken in from CTD pages. Names need to be pipe separated
• DB_info -> links to entity in other database. Database URLs need to be added to github external URL file.

Requested changes to model

WS253

   Biofunction_affected  GO_term_affected   ?GO_term   ?RO_term #Evidence 
    				Gene_affected ?Gene ?RO_term #Evidence
    				Molecule_affected ?Molecule ?RO_term #Evidence
				Other_affected ?Text ?RO_term #Evidence	
				WBProcess_affected   ?WBProcess  ?RO_term #Evidence

• Changes to other models
  • ?Gene
  • ?WBProcess
  • Create ?RO_class //Relationship ontology class populated by RO.obo https://raw.githubusercontent.com/oborel/obo-relations/master/ro.obo the ontology can be browsed here: http://www.ontobee.org/browser/term.php?o=RO&iri=http://www.w3.org/2002/07/owl%23ObjectProperty&graph=http://purl.obolibrary.org/obo/merged/RO

Rationale for WS253 proposed changes

• Biofunction tags

These are to record specific roles, actions, and relationships between molecules and other entities, biofunction role tags were requested by users. Examples of data captured are included below.

    Biofunction_role	Metabolite
				Regulator
				Structural_component
				Cofactor
				Substrate
				Ligand
				Receptor
    Biofunction_affected  GO_term_affected   ?GO_term   ?RO_term #Evidence 
    				Gene_affected ?Gene ?RO_term #Evidence
    				Molecule_affected ?Molecule ?RO_term #Evidence
				Other_affected ?Text ?RO_term #Evidence	
				WBProcess_affected   ?WBProcess  ?RO_term

Examples for molecule biofunction curation

Title: Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2 . 1 and daf-16 . 
Authors: Hashimoto T ; Horikawa M ; Nomura T ; Sakamoto K 
Journal: Biogerontology 
WBPaper00033112 / PMID 19370397
"This result suggests that NAD activates the caloric restriction pathway and DAF-2 / insulin signal pathway independently , and that daf-16 did not contribute to the signaling pathway of caloric restriction " 
"These findings are consistent with previous reports ( Tissenbaum and Guarente 2001 , Yang et al . 2005 ; van der Horst et al . 2004 , 2007 ; Brunet et al . 2004 ) and suggest that NAD activates SIR-2 . 1 , prior to activating the transcriptional activity of DAF-16 "
Molecule: NAD
Biofunction_role: Metabolite
Gene_affected: SIR-2.1  RO: directly activates (RO:0002406)
Gene_affected: DAF-16  RO: increases expression of (RO:0003003)
WBProcess_affected: DAF-2/ insulin signal pathway RO:indirectly activates (RO:0002407) 
---
Title: Genetic and molecular analysis of spe-27 , a gene required for spermiogenesis in Caenorhabditis elegans hermaphrodites . 
Authors: Minniti AN ; Sadler C ; Ward S 
Journal: Genetics 
Year: 1996-05 
Doc ID: WBPaper00002446
"Tyramine release from the RIM ( blue ) activates LGC-55 anion channel , which is expressed in the neck muscles , RMD / SMD motor neurons , and the AVB forward premotor interneuron ( purple ) "
Molecule: Pronase
Molecule: TEA
GO_term_affected: spermatid maturation (GO:0048240) RO:indirectly activates (RO:0002407)
Gene_affected: LGC-55 RO: directly activates (RO:0002406)
---
Title: Identification of a cysteine residue important for the ATPase activity of C . elegans fidgetin homologue . 
Authors: Yakushiji Y ; Yamanaka K ; Ogura T 
Journal: FEBS Lett 
Year: 2004-12-03 
Doc ID: WBPaper00024642
"It was found that ADP strongly inhibits the ATP hydrolysis activity , as little ATPase activity was detected at 3-fold excess of ADP over ATP , suggesting that the F32D1 . 1 ATPase activity may be tightly regulated by the hydrolyzed product ADP"
Molecule: ADP
GO_term_affected: ATP activity (GO:0016887) RO:directly inhibits (RO:0002408)
Gene_affected: F32D1.1 figl-1 RO:directly inhibits (RO:0002408)
---
Title: Bridging the phenotypic gap : real-time assessment of mitochondrial function and metabolism of the nematode Caenorhabditis elegans . 
Authors: Lagido C ; Pettitt J ; Flett A ; Glover LA 
Journal: BMC Physiol 
Year: 2008 
Doc ID: WBPaper00031649
" Azide inhibits complex IV of the mitochondrial respiratory chain by binding reversibly to cytochrome c oxidase [ 24 ] , this arrests the flow of electrons and leads to a decrease in ATP synthesis "
Molecule: Azide
GO_term_affected: mitochondrial electron transport, cytochrome c to oxygen (GO:0006123) RO:directly inhibits (RO:0002408)
GO_term_affected: mitochondrial electron transport, cytochrome c to oxygen (GO:0006123) RO:molecularly interacts with (RO:0002436)
---
Title: Functional analysis of pyrimidine biosynthesis enzymes using the anticancer drug 5-fluorouracil in Caenorhabditis elegans . 
Authors: Kim S ; Park DH ; Kim TH ; Hwang M ; Shim J 
Journal: FEBS J 
Year: 2009-09 
"No proteins exhibited uridine kinase activity when uridine was used as a substrate , but both C29F7 . 3 and F40F8 . 1 produced UDP when UMP was used as a substrate "
Molecule: UMP
Biofunction_role: Substrate
Gene_affected: C29F7.3 RO: input_of RO:0002352 <could use term, substrate_for>
Gene_affected: F40F8.1 RO: input_of RO:0002352
Molecule UDP
Biofunction_role: Metabolite
Gene_affected: C29F7.3 RO:produced_by (RO:0003001) <could use term product_of>
Gene_affected: F40F8.1 RO:produced_by (RO:0003001)
---
Title: Mutations in the Caenorhabditis elegans serotonin reuptake transporter MOD-5 reveal serotonin-dependent and -independent activities of fluoxetine . 
Authors: Ranganathan R ; Sawin ER ; Trent C ; Horvitz HR 
Journal: J Neurosci 
Year: 2001-08-15 
Doc ID: WBPaper00004809
"cat-4 encodes GTP cyclohydrolase I ( C . Loer , personal communication ) , which is required for the synthesis of a biopterin cofactor needed for dopamine and 5-HT biosynthesis ( Kapatos et al . , 1999 ) ."
Molecule: biopterin
Biofunction_role: Cofactor
GO_term_affected: dopamine biosynthesis
GO_term_affected: 5-HT biosynthesis
Gene_affected: cat-4 RO:produced_by (RO:0003001) <could use term product_of>

WS252

?Molecule Name ?Text //WBMoleculeID
          Public_name ?Text
          Formula ?Text //imported from ChEBI
          Monoisotopic_mass ?Float //need to set up automated calculation based on formula
          IUPAC ?Text //imported from ChEBI
          SMILES ?Text //imported from ChEBI
          InChi ?Text //imported from ChEBI
          InChiKey ?Text //imported from ChEBI
          Synonym ?Text //mainly from CTD, but also from papers and ChEBI
          DB_info Database ?Database ?Database_field ?Text //links molecule to ChEBI, CTD, KEGG, etc
          Status Detected #Evidence
                 Predicted #Evidence
          Detection_method ?Text #Evidence //NMR, MALDI-MS, HPLC-UV, shotgun lipidomics
          Extraction_method ?Text #Evidence //MeOH, exometabolome, MeOH/Chloroform, 5% trichloroacetic acid
          Nonspecies_source ?Text
          Chemical_synthesis #Evidence
          Endogenous_in ?Species #Evidence
          Biofunction_role Metabolite #Evidence //note there is no ?Text, which is part of the other Biofunction_role tags
                           Regulator ?Text #Evidence
                           Structural_component ?Text #Evidence
                           Cofactor ?Text #Evidence
                           Activator ?Text #Evidence
                           Inhibitor ?Text #Evidence
                           Product ?Text #Evidence
                           Substrate ?Text #Evidence
                           Ligand ?Text #Evidence
                           Receptor ?Text #Evidence
          Essential_for ?Species #Evidence
          WBProcess ?WBProcess XREF Molecule
          Regulate_expr_cluster ?Expression_cluster XREF Regulated_by_molecule    // Wen WS228
          Affects_phenotype_of Variation ?Variation ?Phenotype #Evidence
                               Strain ?Strain ?Phenotype #Evidence
                               Transgene ?Transgene ?Phenotype #Evidence
                               RNAi ?RNAi ?Phenotype #Evidence
                               Rearrangement ?Rearrangement ?Phenotype #Evidence
          Interaction ?Interaction XREF Molecule_interactor // Chris WS244
          Molecule_use ?Text #Evidence
          Reference ?Paper XREF Molecule
          Remark

Rationale for WS252 changes

• New id tags

The following tags were requested by a user, these are important for metabolomics analysis and can be supplied by ChEBI (except monoisotopic mass, which can come from KEGG)

 
    Formula ?Text
    Monoisotopic_mass ?Float
    IUPAC ?Text
    SMILES ?Text
    InChi ?Text
    InChiKey ?Text

• Status tag

User requested we include if a molecule has been detected in the worm or if it has only been predicted, detection and extraction methods support if a molecule has been detected

    Status  Detected  #Evidence
            Predicted #Evidence
    Detection_method ?Text #Evidence //NMR, MALDI-MS, HPLC-UV, shotgun lipidomics
    Extraction_method ?Text #Evidence //MeOH, exometabolome, MeOH/Chloroform, 5% trichloroacetic acid

• Source tags

User requested that we indicate if the molecule is made endogenously in the worm or if it is an essential molecule needing to be supplied from elsewhere

    Chemical_synthesis #Evidence //Requested by F.Schroeder to index chemically synthesized molecules
    Nonspecies_source ?Text 
    Endogenous_for ?Species #Evidence                         
    Essential_in ?Species #Evidence

• Biofunction_role tags

These are to record specific roles, actions, and relationships between molecules and other entities, biofunction role tags were requested by users and should make them easy to mine from the database.

          Biofunction_role Metabolite ?Text #Evidence
                           Regulator ?Text #Evidence
                           Structural_component ?Text #Evidence
                           Cofactor ?Text #Evidence
                           Activator ?Text #Evidence
                           Inhibitor ?Text #Evidence
                           Product ?Text #Evidence
                           Substrate ?Text #Evidence
                           Ligand ?Text #Evidence
                           Receptor ?Text #Evidence

 ///////////////////////////////////////////////////////////////////////////////////

Corresponding changes in touched models

/////
?Phenotype_info    Affected_by  Molecule  ?Molecule    #Evidence
/////

/////
?Gene_regulation  Regulator Molecule_regulator   ?Molecule  XREF  Gene_regulator  #Boolean 
/////

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"
• Database "SMID-DB"

ChEBI

ChEBI terms and IDs are pulled from the chebi.obo on the ChEBI ftp server. This file is updated monthly (first Monday of the month except in the case of a Bank Holiday when it becomes the Tuesday). The ChEBI website is updated daily.

chebi.obo is stored on tazendra here: /home/postgres/work/pgpopulation/obo_oa_ontologies

Syncing with ChEBI scripts

find_missing_chebi_in_other_oa.pl
identifies any molecule in the mop tables with no mop_chebi id but has been used in curation through paper tables of either mop, app, grg, pro, or rna tables. The output lists molecules that have not been manually matched to with a ChEBI ID - these are of three types:
1. exists in chebi.obo - if so, manually fill in chebi ID
2. does not exist in chebi.obo but can be requested - if so, request term from chebi
3. does not exist in chebi.obo and cannot be requested - most likely the molecule is a protein or complex, neither are curated by chebi, e.g., Shiga Toxin, BTtoxin, streptolysin. Currently there is no alternative database to link these things to - should at some point see if there is UniProt id for them.

/home/acedb/karen/molecule/chebi_missing/find_missing_chebi_in_other_oa.pl

checks molecule entries without chebi that have data for any of :
app_molecule
grg_moleculeregulator
pro_molecule
rna_molecule
mop_paper

print out mop_publicname mop_molecule mop_chemi mop_paper mop_smmid
as well as corresponding papers from other OAs.  aggregate all papers
for a given molecule objects, convert to PMID if pmid exists.

Output at file 'out'

output looks like this:
 
WBMol:00000139	Oxamniquine
mop	139
mop_chemi	21738-42-1
mop_molecule	D010073
mop_paper	"WBPaper00038322","WBPaper00031181"
aggregatedWBPapers	WBPaper00031181, WBPaper00038322
aggregatedWBPmids	pmid17988075, pmid21500322

WBMol:00000155	icariin
mop	155
mop_chemi	489-32-7
mop_molecule	C056599
mop_paper	"WBPaper00040566"
aggregatedWBPapers	WBPaper00040566
aggregatedWBPmids	pmid22216122

compare_chebi.pl(2015 11 04)
The goal of this script is to import more IDs from ChEBI into the mop_tables. The import relies on mop entries matching chebi objects. So the first thing the script does is to compare chebi.obo object name with mop_publicname and mop_synonym, in a case insensitive way. chebi.obo comes from ftp://ftp.ebi.ac.uk/pub/databases/chebi/ontology/chebi.obo

The script outputs three files:

• chebis_in_mop_vs_obo - compares chebi.obo and mop tables, finds molecules in mop tables that do not exist in the chebi.obo - based on name,

100241 not in mop
100246 not in mop
100461 not in mop
100921 not in chebi
101085 not in mop
101096 not in mop

• chebi_name_discrepancies_case_sensitive and *chebi_name_discrepancies

These files list the mop values with chebi IDs but where the public names or synonyms do not match - the first file forces case sensitivity so there are many instances where the names are the same, it's just a matter of case (467 lines). The second file is case insensitive, this was much shorter (73 lines). I went through these manually and verified the entities were the same, there are two confusions:

CHEBI:30829 petroselaidic acid (CasRN 593-40-8) MOP- petroselinic acid (CasRN 4712-34-9) CHEBI:53692 hypaque (CasRN 117-96-4) MOP histopaque (CasRN 737-31-5)

Once names are matched, the corresponding values will be imported into mop_tables as follows: mop_table chebi.obo entry example mop_formula synonym: "<formula>" RELATED FORMULA [ChEBI:] (changed) mop_iupac (table not created?) synonym: "<NAME>" EXACT IUPAC_NAME [IUPAC:] mop_smiles synonym: "<smiles>" RELATED SMILES [ChEBI:] mop_inchi synonym: "<InChI=>" RELATED InChI [ChEBI:] mop_inchikey synonym: "<inchikey>" RELATED InChIKey [ChEBI:] mop_kegg KEGG COMPOUND:C00742 "KEGG COMPOUND" (added)

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.

--kjy 20:03, 16 December 2011 (UTC)

Molecule OA

Changes for WS252

• syncing with chebi.obo

 on manoglassi /home/postgres/work/pgpopulation/mop_molecule/20151104_chebi_again/
 chebis_in_mop_vs_obo - chebi IDs in one file but not the other
 chebi_name_discrepancies - among chebi IDs that exist in both sets, when no name or synonym match the other
 compare_chebi.pl - works off of chebi.obo, can run in own directory with updated chebi.obo (copy script to directory with new version of chebi.obo)

 on mangolassi /home/postgres/work/pgpopulation/mop_molecule/20151104_chebi_again/populate_other_chebi.out
 Output tells you if a chebiID does not exist. 
 'HAS MOP' are entries that have an obo and mop value 
 same vs diff is whether what's in obo and mop is the same or different

 /home/postgres/work/pgpopulation/mop_molecule/20151104_chebi_again/populate_other_chebi.pl

mop_table	chebi.obo entry	example
mop_molformula	synonym: "<formula>" RELATED FORMULA [ChEBI:]  (changed)
mop_iupac (table not created?)	synonym: "<NAME>" EXACT IUPAC_NAME [IUPAC:]
mop_smiles	synonym: "<smiles>" RELATED SMILES [ChEBI:]
mop_inchi	synonym: "<InChI=>" RELATED InChI [ChEBI:]
mop_inchikey	synonym: "<inchikey>" RELATED InChIKey [ChEBI:]
mop_kegg  KEGG COMPOUND:C00742 "KEGG COMPOUND"  (added)

• pgpopulation script

for incorporating chebi values for the new tables (except mop_molformula)

• • should replace all the KEGG compound ids with what is in the chebi.obo if the KEGG compound id in mop_kegg is missing. If the KEGG compound ids are different in chebi.obo vs mop_kegg, replace the value with the chebi.obo value and report the discrepancy in the output.

Initial mop tables

For entering, editing, and storing information about molecule objects.

on tazendra or mangolassi:
~postgres/public_html/cgi-bin/oa/wormOA.pm

&initWormFields is like a switch to load a specific OA, each of them has a 3 letter code that corresponds to the postgres table name. so 'mop' is for the molecule oa and the 'mop_'

s in postgres mop then calls &initWormMopFields.
currently around line 1200 there are sets of hashes like :

 $fields{mop}{id}{type}                             = 'text';
 $fields{mop}{id}{label}                            = 'pgid';
 $fields{mop}{id}{tab}                              = 'all';
 $fields{mop}{paper}{type}                          = 'multiontology';
 $fields{mop}{paper}{label}                         = 'WBPaper';
 $fields{mop}{paper}{tab}                           = 'all';
 $fields{mop}{paper}{ontology_type}                 = 'WBPaper';
 $fields{mop}{name}{type}                           = 'text';
 $fields{mop}{name}{label}                          = 'Name';
 $fields{mop}{name}{tab}                            = 'all';

most of these correspond to a postgres table. the first one is the exception, which is the pgid. so excluding that in the example above, there are 2 postgres tables, mop_paper and mop_name

• {type} is the type of data they hold
  • text
  • bigtext
  • ontology
  • dropdown
  • toggle
  • multiontology
  • multidropdown
• {label} is the field name in the OA
• {tab} is which tab number it should show in. 'all' shows up in

all tabs, but is mostly used in OAs with no numbered tabs

• {ontology_type} if {type} is ontology / multiontology, ontology_type

refers to the type of values that go there for the autocomplete and validation.

• {ontology_table} if the type is ontology / multiontology

 $fields{mop}{chebi}{type}                          = 'ontology';
 $fields{mop}{chebi}{label}                         = 'ChEBI_ID';
 $fields{mop}{chebi}{tab}                           = 'all';
 $fields{mop}{chebi}{ontology_type}                 = 'obo';
 $fields{mop}{chebi}{ontology_table}                = 'chebi';

which corresponds to the obo_ tables that are updates via cronjob or populated just once. in this case mapping to obo_<name|data|syn>_chebi

• {dropdown_type} if the {type} is dropdown, which refers to the type of data like the {ontology_type}, but the values are hardcoded further down in the code instead of stored in postgres for querying.

mop_tables

postgres tables for the Molecule class
dumper on tazendra at karen/Molecule/dump_molecule_ace.pl

WSVersion	Model tag	table	type	OA label	tab	ontology_type	ontology_table	cross table population script	comment
	pgonly	mop_id	not a table	pgid	all*	-	-	-	WBMol: $molId = &pad8Zeros($newPgid)
	pgonly	mop_timestamp	not a table	none	-	-	-	-
	pgonly	mop_curator	dropdown	Curator	all	-	-	-	same values in all OA curation tables
Name	mop_name	text	Name	all	-	-	-	WBMolID -added after tables were built
Public_name	mop_publicname	bigtext	Public_name	all	-	-	-
Synonym	mop_synonym	bigtext	Synonyms	all	-	-	-
DB_info	mop_molecule	text	MeSH / CTD or default	all	-	-	-	use MeSh ID here originally used as Name
DB_info	mop_chemi	text	CasRN	all	-	-	-
DB_info	mop_chebi	ontology	ChEBI_id	all	obo	chebi		downloaded from ChEBI server, which is updated monthly, ftp://ftp.ebi.ac.uk/pub/databases/chebi/ontology/chebi.obo
DB_info	mop_kegg	text	Kegg compound (Acc#)	all	-	-	-
Remark	mop_remark	bigtext	Remark	all	-	-	-
Reference	mop_paper	multiontology	WBPaper	all	WBPaper	pap_tables	-
Molecule_use	mop_moleculeuse	bigtext	Molecule use	all	-	-	-
Not in model	mop_gotarget	multiontology	GO target	all	obo	goid	-
Not in model	mop_genetarget	multiontology	Gene target	all	WBGene	gin_tables	-
DB_info	mop_smmid	text	SMID-DB	all	-	-	-
Gene_regulation	grg_moleculeregulator	multiontology	Molecule Regulator	GENEREG tab3	Molecule	mop_tables	-
WBProcess	pro_molecule	multiontology	Molecule	PROCESS tab1	Molecule	mop_tables	-
Phenotype	app_molecule	multiontology	Molecule	PHENOTYPE tab2	Molecule	mop_tables	-
RNAi	rna_molecule	multiontology	Molecule	RNAi tab2	Molecule	mop_ tables	-
Interaction	int_moleculenondir int_moleculeone int_moleculetwo	Molecule	Effected molecule Affected molecule Nondirectional molecule	INTERACTION tab3	Molecule	mop_tables	-	Molecule were initially curated through a/effected_other fields and stored as text in a field in tab4.

• "all" can mean all tabs, but also is used for OA's that only have one tab.

Molecule list

Molecule names have changed to WBMoleculeIDs
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 has been pared down and 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 and available based on frequency in corpus and concatenated into one file
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

Molecule upload

• Molecule.ace made from karen/Molecule/dump_molecule_ace.pl
• Database info for the chemical/small molecule database links needs to be manually edited on github in the external_urls file whenever there are changes to the databases associated with molecule data.

During each upload a molecule.ace file will be made in citace by Wen. This file will contain all the molecule cross references from within the RNAi and Variation Phenotype curation, merging 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