Selected PathoLogic Refining Tasks

1
Selected PathoLogic Refining Tasks

• Creation of Protein Complexes
• Assignment of Modified Proteins
• Operon Prediction

2
Creating Protein Complexes

• Refine -gt Create Protein Complexes
• When multiple polypeptides catalyze the same
  reaction
• Could be isozymes ? Do nothing
• Could be components of a complex
• Software cant tell the difference

3
Manually-assisted Complex Creation

• Curators decide based on
• Names, e.g. subunit A, subunit B
• How enzyme is organized in other organisms
• Members of a complex are often neighbors on
  chromosome
• Specific biological knowledge based on
  literature, etc.

• Complex creation tool
• Lists names, gene IDs
• Shows reaction in MetaCyc
• Indicates which genes are neighbors
• Leaves final decision up to curator

4
Creating Protein Complexes
5
Complex Subunit Stoichiometries

• Leave coefficients blank if unknown

6
Proteins that are Reaction Substrates

• Reactions are defined in MetaCyc with protein
  classes as substrates
• Need to find which genes in the genome code for
  instances of those classes.
• Refine -gt Assign Modified Proteins
• Finds all reactions that
• Have an enzyme
• Have a protein class as substrate
• Name search for substrate
• Presents possibilities, asks curator to choose
• Chosen protein will be made a child of the
  protein class

7
Proteins as Reaction Substrates
8
Operon Predictor

• Refine -gt Predict Transcription Units

9
Nomenclature

• WO pair pair of genes within an operon
• TUB pair pair of genes at a transcription unit
  boundary (delineate operons)

10
Operation of the operon predictor

• For each contiguous gene pair, predict whether
  gene pairs are within the same operon or at a
  transcription unit boundary
• Use pairwise predictions to identify potential
  operons
• AB TUB pair
• BC WO pair operon BCD
• CD WO pair
• DE TUB pair

A
B
C
D
E
11
Operon predictor

• We use method from Salgado et al, PNAS (2000) as
  a starting point.
• Uses E. coli experimentally verified data as a
  training set.
• Compute log likelihood of two genes being WO or
  TUB pair based on intergenic distance.
• Predicts operon gene pairs based on
• intergenic distance between genes
• genes in the same functional class

12
Operon predictor

• Additional features easily computed from a PGDB
• both genes products enzymes in the same metabolic
  pathway
• both gene products monomers in the same protein
  complex
• one gene product transports a substrate for a
  metabolic pathway in which the other gene product
  is involved as an enzyme
• a gene upstream or downstream from the gene pair
  (and within the same directon) is related to
  either one of the genes in the pair as per
  features 1, 2 and 3 above.