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Advanced PGDB Editing: Regulation GO Terms Ingrid M. Keseler Bioinformatics Research Group SRI International [email protected] 1 SRI International Bioinformatics Motivation: Why Regulation? For example: • Genome and regulatory overview Global perspective Omics data • Data sets for promoter prediction etc. 2 SRI International Bioinformatics Omics Viewer: Regulatory Overview Data from J Bacteriol. 2010 Feb;192(3):870-82. A comprehensive proteomics and transcriptomics analysis of Bacillus subtilis salt stress adaptation. 3 SRI International Bioinformatics Defining a New Transcription Unit • Gene > New Operon • Key elements – gene names in order PTools will prompt you for a citation for the TU • Specify promoter Can use absolute or relative position of transcription start site PTools will calculate the other value for you PTools will prompt you for a citation for the TSS • Specify sigma factor (if appropriate) It may be necessary to first classify sigma factors under |Sigma-Factors| 4 SRI International Bioinformatics Adding Transcription Factor Binding Sites • Click on TU name – Edit > Create Regulatory Interaction • Select type of regulatory interaction • Can put in a protein name, or select a defined TF • Indicate whether it activates, represses or both • Define relative distance from transcription start site Draws DNA footprint from feature defined in TF • Can edit TF binding sites by clicking on site name Edit > Regulatory Interaction Editor • Can add summaries and citations • This builds the transcriptional regulatory network 5 SRI International Bioinformatics More Regulatory Interactions • Attenuation • Regulation of translation • RNA-mediated • Protein-mediated • Small molecule-mediated • Regulated protein or mRNA degradation (planned) • If you have suggestions for types of regulation you would like to represent, or for improvements on what is there, please let us know. • Tools for genome-scale datasets? 6 SRI International Bioinformatics Gene Ontology (GO) Terms 7 SRI International Bioinformatics Motivation: Why GO Terms? For example: • Standardization of annotation Data mining across genomes Genome annotation by similarity (e.g. via InterPro, Pfam, TIGRFAM, COG mappings) • Microarray data clustering • Etc. 8 SRI International Bioinformatics A Word (Or Two) About GO • Learn what you can about using GO Surf the geneontology.org web site Attend a GO Annotation Camp Ask questions on the GO mailing lists • Request new GO terms if appropriate Useful for everybody Have input when it counts A new GO database can be incorporated into Pathway Tools; request help with setting up the process 9 Computational GO term assignments may be available for your genome via UniProt SRI International Bioinformatics GO Classification Editor • Accessible via the Protein Editor Expand/contract, select/deselect by clicking on +/- and the actual terms Selected items move to “Selections” section Search feature: can search by name/substring or GO id (in the full format only, e.g. “GO:0007165”, not just the number) 10 For example, search for “arginine” yields many options Click an option to highlight in hierarchy Hovering over a term in the hierarchy brings up its definition in the middle panel Must still click on entry in hierarchy to select the term for annotating the protein SRI International Bioinformatics