1. SRI International Bioinformatics 1 The Regulation Summary Diagram Suzanne Paley Pathway Tools Workshop 2010

2. SRI International Bioinformatics 2 How can Protein Levels and Function be Regulated? Transcription Initiation – transcription factors Transcription Initiation – sigma factors Attenuation (various kinds) Translation (various kinds) Post-translational modification Complex formation Cofactors Substrate-level modulation Degradation

3. SRI International Bioinformatics 3 Motivations and Design Factors Combine all forms of regulation into a single unified diagram Diagram should be intuitive to a biologist l Several biologists involved in design process Diagram is automatically generated from the data – no manual tweaking! Diagram should be compact, mostly horizontal OK to omit low-level details

4. SRI International Bioinformatics 4 Example: trpD Organized around biology’s central dogma: DNA - > RNA -> protein Green indicates activation, magenta indicates inhibition (both defined loosely) Things to notice: Transcription factor with ligand Sigma factor Operon organization Attenuation leads to truncated mRNA Substrate-level regulation of complex

5. SRI International Bioinformatics 5 Example: oppD Things to notice: Ligands can either activate or inhibit transcription factors Translational regulation Riboswitch Small RNA, with accessory protein Multiple complexes

6. SRI International Bioinformatics 6 Example: bglG Things to notice: Transcription factors grouped: activators, inhibitors Positive attenuation points to full-length mRNA Post-translational phosphorylation

7. SRI International Bioinformatics 7 More Examples: glnG, speD Things to notice: Multiple sigma factors Dual transcription factors Regulation of post-translational modification Post-translational cleavage and complexation

8. SRI International Bioinformatics 8 Where Does Diagram Appear? Gene/Gene product pages Not in eukaryotic or multi-organism PGDBs Is diagram useful when no regulation? l Regulation information must be curated, not inferred by PathoLogic l In PGDBs with no curated regulation information, diagram does not appear for any gene l Otherwise, it appears for every gene PGDBs with regulatory information: l EcoCyc l BsubCyc