Labeling%20Semantic%20Relations%20Between%20Proteins

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Labeling Semantic Relations Between Proteins

• Barbara Rosario, Marti Hearst, Janice Hamer

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Protein-Protein interactions

• One of the most important challenges in modern
  genomics, with many applications throughout
  biology
• There are several protein-protein interaction
  databases (BIND, MINT,..), all manually curated

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HIV-1 Protein Interaction Database

• Documents interactions between HIV-1 proteins and
  
• host cell proteins
• other HIV-1 proteins
• disease associated with HIV/AIDS
• 2224 pairs of interacting proteins, 65 types

http//www.ncbi.nlm.nih.gov/RefSeq/HIVInteractions
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HIV-1, Protein Interaction Database
Protein 1 Protein 2 Paper ID Interaction Type
Tat, p14 AKT3 11156964, 11994280.. activates
AIP1 Gag, Pr55 14519844, binds
Tat, p14 CDK2 9223324 induces
Tat, p14 CDK2 7716549 enhances
Tat, p14 CDK2 9525916 downregulates
.
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Most common interactions
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Protein-Protein interactions

• Idea use this to label data

Protein 1 Protein 2 Interaction Paper ID
Tat, p14 AKT3 activates 11156964
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Protein-Protein interactions

• Idea use this to label data

Protein 1 Protein 2 Interaction Paper ID
Tat, p14 AKT3 activates 11156964
Extract from the paper all the sentences with
Protein 1 and Protein 2
activates
activates

Label them with the interaction given in the
database
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Protein-Protein interactions

• Use citances
• Find all the papers
• that cite the papers
• in the database

Protein 1 Protein 2 Interaction Paper ID
Tat, p14 AKT3 activates 11156964
ID 9918876
ID 9971769
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Protein-Protein interactions

• From the papers, extract
• the citation sentences
• from these extract the
• sentences with Protein 1
• and Protein 2
• Label them

Protein 1 Protein 2 Interaction Paper ID
Tat, p14 AKT3 activates 11156964
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Examples of sentences

• Papers
• The interpretation of these results was slightly
  complicated by the fact that AIP-1/ALIX depletion
  by using siRNA likely had deleterious effects on
  cell viability , because a Western blot analysis
  showed slightly reduced Gag expression at later
  time points (fig. 5C ).
• Citations
• They also demonstrate that the GAG protein from
  membrane - containing viruses , such as HIV ,
  binds to Alix / AIP1 , thereby recruiting the
  ESCRT machinery to allow budding of the virus
  from the cell surface (TARGET_CITATION CITATION
  ) .

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10 Interaction types
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Protein-Protein interactions

• Tasks
• Given sentences from Paper ID, and/or citation
  sentences to ID
• Predict the interaction type given in the HIV
  database for Paper ID
• Extract the proteins involved
• 10-way classification problem

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Protein-Protein interactions

• Models
• Dynamic graphical model
• Naïve Bayes

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Graphical Models
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Evaluation

• Evaluation at document level
• All (sentences from papers citations)
• Papers (only sentences from papers)
• Citations (only citation sentences)
• Trigger word approach
• List of keywords (ex for inhibits inhibitor,
  inhibition, inhibitetc.
• If keyword presents assign corresponding
  interaction

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Results

• Accuracies on interaction classification

Model All Papers Citations
Markov Model 60.5 57.8 53.4
Naïve Bayes 58.1 57.8 55.7
Baselines
Most freq. inter. 21.8 11.1 26.1
TriggerW 20.1 24.4 20.4
TriggerW BO 25.8 40.0 26.1
(Roles hidden)
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Results confusion matrix
For All. Overall accuracy 60.5
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Hiding the protein names

• Replaced protein names with tokens PROT_NAME
• Selective CXCR4 antagonism by Tat
• Selective PROT_NAME antagonism by PROT_NAME

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Results with no protein names
Model Papers Citations
Markov Model 44.4 (-23.1) 52.3 (-2.0)
Naïve Bayes 46.7 (-19.2) 53.4 (-4.1 )
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Protein extraction

• (Protein name tagging, role extraction)
• The identification of all the proteins present in
  the sentence that are involved in the interaction
• These results suggest that Tat - induced
  phosphorylation of serine 5 by CDK9 might be
  important after transcription has reached the 36
  position, at which time CDK7 has been released
  from the complex.
• Tat might regulate the phosphorylation of the RNA
  polymerase II carboxyl - terminal domain in pre -
  initiation complexes by activating CDK7

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Protein extraction results
Recall Precision F-measure
All 0.74 0.85 0.79
Papers 0.56 0.83 0.67
Citations 0.75 0.84 0.79
No dictionary used
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Conclusions of protein-protein interaction project

• Encouraging results for the automatic
  classification of protein-protein interactions
• Use of an existing database for gathering labeled
  data
• Use of citations