----------------------------------------------- Pentacon NSAID Project Curation Princeton University, NJ, USA University of Pennsylvania, PA, USA ----------------------------------------------- Readme file name: BP_AAE_genelist_Readme_20141013_production.txt Readme for the following files: BP_AAE_genelist_20141013_production.txt Total Number of Genes: 87 (61 BP, 30 AAE), 4 genes are on both BP and AAE Number of Gold Standard (Direct) Genes: 2 BP, 17 AAE Number of Likely (Indirect) Genes: 23 BP, 5 AAE Number of Predicted Genes: 36 BP, 8 AAE Version: Production Date: 10/13/2014 Curation Overview ----------------- This list was started March 14, 2013, and the last gene (Q13018) was added on 07/02/2013. This gene list was updated 08/14/2014. The curation process involved creating a list of genes from Reactome pathways (pathways annotated with experimental evidence) identified as related to the phenotype of blood pressure, experimentally-supported GO annotations for blood pressure, and the literature. The genes for the identified Reactome pathways were taken from "Reactome Pathways Gene Set." Genes obtained from GO were assembled from those directly annotated to "regulation of blood pressure" (GO:0008217), "regulation of blood vessel size" (GO:0050880), and manually-selected children of these two terms. A similar query of GO was carried out for arachidonic acid metabolism related GO terms (described in detail in the link "Arachidonic acid metabolism related GO annotations"). Genes associated with arachidonic acid metabolsm (in a regulatory manner) found in literature by curators have also been added to this list in the gene set AAE. The search was restricted to experimental annotations. Gene Set Qualifiers are assigned based solely on the evidence presented in the papers in the file BP_AAE_genelist_20141013_preliminary.txt. ONLY papers contained within this spreadsheet have been reviewed. No other papers have been reviewed. These Gene Set Qualifiers were assigned as described below. When more evidence is added, the assignment of Gene Set Qualifiers may change. The BP GO annotations are available here: https://docs.google.com/spreadsheet/ccc?key=0Aq_I_6K-fUKqdGxpcFdqOS1zWC14NDlWSElCeFgxbVE#gid=2 The Reactome Pathways Gene Set was downloaded on 3/11/2013. This list, which may have been updated by Reactome, is available here: http://www.reactome.org/download/index.html The list of arachidonic acid metabolism genes are available here: https://docs.google.com/spreadsheet/ccc?key=0Avit99d8o9hWdDh0Q3dMeU5lbmV1ejlnQmF1YW9MWFE#gid=14 Arachidonic acid metabolism related GO annotations are available here: https://docs.google.com/a/itmat.upenn.edu/spreadsheets/d/1b9iPl_Jw8q1l53bvOY6B-1Z-TQHicMICM3U0UzHc6kg/edit#gid=259971399 -------------------------------------------------------------- BP_AAE_genelist_20141013_production.txt File Information -------------------------------------------------------------- Curation files: ---------------------- Public file(s): BP_AAE_genelist_20141013_production.txt All_genes is comprised of Gold Standard (Direct), Likely (Indirect), and Predicted genes. Columns for "BP_AAE_genelist_20141013_production.txt" file: ---------------------------------------------------------------------------- (---Notes provided for specific columns where applicable.) Gene Set AAP is used for genes directly involved in the 'arachidonic acid pathway'. AAE is used for genes related to the arachidonic acid pathway. BP is used for genes related to the phenotype of blood pressure. Gene Set Qualifier Genes were assigned a qualifier (Gold Standard, Likely, or Predicted) based on the level of evidence supporting involvement in the pathway or phenotype captured by the column Gene Set. See notes below for details about the assignment of gene set qualifiers. Gene Name Alternative Names Recommended Name UniProt ID NCBI Gene ID EC Species Name Taxonomy ID Pathway This column denotes the name of a pathway in which the gene is listed as participating by the Information Source Information Source GO - Gene Ontology: http://www.geneontology.org Reactome: http://www.reactome.org When Reactome is the information source, the stable identifer is used. This looks like: REACT_147707.2. Genes identified from GO blood pressure annotations have GO:BP. 'Literature' denotes that genes were added based on evidence present in literature reviews; this information source should be accompanied by entries in the Pubmed ID column. Evidence Type The evidence code C is used to denote review articles. The evidence code E is used for articles that present experimental evidence including, but not limited to, tissue distribution and enzyme characterization. The evidence code P is used for publications that (1) predict presence based on evidence in mice/rabbits (2) use bioinformatics tools to identify human genes and (3) contain non-traceable author statements. Bioinformatics approaches would include using conserved sequence motifs to identify candidate genes, using a known human gene to identify sequences with significant identity (and finding cDNA in EST database). If there are multiple Pubmed IDs in the PubMed ID column, but only one evidence code in the Evidence Type column, it means that all Pubmed IDs were assigned the same evidence code. If there are multiple reference codes, each evidence code correlates with each corresponding PMID in the PubMed ID column. PubMed ID Notes Notes/SubPathway Notes/SubPathway are assigned by Pentacon curators Gene Set Qualifiers for gene list BP ---------------------------------------------------------------------------- Gold Standard (Direct) The gene set qualifier "Gold Standard" is assigned when experimental evidence demonstrates involvement of the gene in BP regulation in humans. Experimental evidence means (a combination of): - mutations were found in the gene found in people displaying the phenotype of interest, in this case altered BP, and there is associate familial evidence showing that individuals without the mutation do not display the phenotype - drugs produce a change in phenotype in humans by targeting a gene in the list - Mendelian disease Genes assigned the "Gold Standard" gene set qualifier can be used for computational analyses. Likely (Indirect) The gene set qualifier "Likely" is assigned when genes ‘likely’ participate in the regulation of BP in humans. Genes are assigned "Likely" when the experimental evidence is not a direct measure of BP. Examples: - in vitro/ex vivo evidence only, such as vasoconstriction - genetic association studies and mouse KO study showing physiological evidence of gene involved in regulation of BP - phenotype observed in an organism (eg. change in BP in mice) and in vitro in human study These genes can be included in a computational analysis based on programmer discretion. Predicted The gene set qualifier "Predicted" is assigned when genes have been inferred to be involved in BP regulation based on: - evidence from other organisms - only in vitro evidence for human genes that demonstrate that an expressed gene has a given function (eg PC5 when co-expressed with a prorenin expression vector results in cells secreting renin) - only genetic association study (no familial evidence) These genes should not be used in a computational analysis. Gene Set Qualifiers for gene list AAE are the same as for gene list AAP https://docs.google.com/spreadsheet/ccc?key=0AlaXVt5NnxhMdHZ2YnlpYWV6bk5hRmhOWWU3UjFZNHc#gid=14 ---------------------------------------------------------------------------- For questions please contact Rose Oughtred (rose at genomics.princeton.edu). ----------------------------------------------------------------------------