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The Regulation Summary Diagram

Suzanne Paley

Pathway Tools Workshop 2010

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How can Protein Levels and Function be Regulated?

Transcription Initiation – transcription factorsTranscription Initiation – sigma factorsAttenuation (various kinds)Translation (various kinds)Post-translational modificationComplex formationCofactorsSubstrate-level modulationDegradation

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Motivations and Design Factors

Combine all forms of regulation into a single unified diagram

Diagram should be intuitive to a biologist Several biologists involved in design process

Diagram is automatically generated from the data – no manual tweaking!

Diagram should be compact, mostly horizontalOK to omit low-level details

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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

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Example: oppD

Things to notice:• Ligands can either activate or inhibit transcription factors• Translational regulation

• Riboswitch• Small RNA, with accessory protein

•Multiple complexes

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Example: bglG

Things to notice:• Transcription factors grouped: activators, inhibitors• Positive attenuation points to full-length mRNA• Post-translational phosphorylation

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More Examples: glnG, speD

Things to notice:• Multiple sigma factors• Dual transcription factors• Regulation of post-translational modification• Post-translational cleavage and complexation

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Where Does Diagram Appear?

Gene/Gene product pagesNot in eukaryotic or multi-organism PGDBsIs diagram useful when no regulation?

Regulation information must be curated, not inferred by PathoLogic

In PGDBs with no curated regulation information, diagram does not appear for any gene

Otherwise, it appears for every genePGDBs with regulatory information:

EcoCyc BsubCyc