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Finding Contradictions, Contrasts and 
Negations in Protein­Protein Interactions
in the Biomedical Literature
Using Text Mining

 Farzaneh Sarafraz

 COMP7000 Presentation
 Text Mining Group
 Supervised by Dr. Goran Nenadić
 28 November 2008
                            
Natural Language Processing
a.k.a Computational Linguistics




                    
Natural Language Processing




                   
Natural Language Processing




                   
Text

        Easily shared
    



        Primary information source
    



        Most up­to­date
    




        Unstructured
    



        No explicit data
    




                              
Text Mining




                   IE
          IR            DM




                
Finding Contradictions, Contrasts and 
Negations in Protein­Protein 
Interactions
in the Biomedical Literature
Using Text Mining




                    
Text Mining in Biomedicine

        Biomedical Scientific Literature




        >17M articles from >5K journals 



        since 1950s adding 2000 every day
        Impossible for humans to manage




        Specific (rather peculiar) language





                                  
Finding Contradictions, Contrasts and 
Negations in Protein­Protein 
Interactions
in the Biomedical Literature
Using Text Mining




                    
Protein­Protein Interactions




                     
Protein­Protein Interactions




                     
Finding Contradictions, Contrasts and 
Negations in Protein­Protein 
Interactions
in the Biomedical Literature
Using Text Mining




                    
Example

        quot;Our results indicate that gp120 from two 
    


        different strains of HIV binds to a larger 
        region of the CD4 protein than previously 
        described.quot;




                                
Example

        gp120 synonyms
    


                                           −   gp41
        −   Transmembrane Glycoprotein     −   TM
        −   Envelope Glycoprotein          −   ENV
        −   Surface Glycoprotein           −   HIV­1 gp8
        −   SU
        −   gp160
        −   Envelope Surface Glycoprotein gp160 Precursor

                                     
Example

        Binds is almost the same as
    


        −   Interacts with
        −   Frictionates
        −   Associates with
        −   Activates
        −   Colocalizes with
        −   Cleaves


                                
Example

        CD4 can be expressed as
    




         CD4+ T     T4(CD)     CD4+ (T)       CD4(+) T cell
         CD4­, T    CD4 (T)    CD4(T)         CD4 T­cell
         T CD4      CD4(+)T    CD(4+) T       CD4(+) T­cell
         CD4(+) T   CD4+­T     CD4­ T         CD4(+)T cell
         CD4 T      CD4(+)­T   CD4+ T cell    CD4+­T­cell
         T4+ (CD)   CD4+T      CD4­, T cell   CD4(+)­T­cell
         T4 (CD)    T (CD4)    CD4+ T­cell    CD4 T cell




                                   
Even after all this...

        The chimpanzee­based CD4(81­92) peptide, 
    


        however, which differs from the human peptide 
        by a single amino acid substitution (E for G) at 
        position 87, was considerably less potent than 
        the human CD4(81­92)­based peptide congener 
        to inhibit HIV­1­induced cell­cell fusion.




                               
Contradiction and Contrasts

        Author A reports p
    



        Author B reports ¬p
    




        We have p under conditions q
    



        But we have ¬p under conditions q'
    




                               
Negations

        Linguistic
    


        −   quot;Protein A does not interact with protein B.quot;
        −   quot;We lack evidence that A interacts with B.quot;



        Biological
    


        −   quot;Protein A inhibits protein B.quot;
        −   dephosphorylates / depolymerizes
        −   downregulates (vs. upregulates)
                                     
        −   etc.
Finding Contradictions, Contrasts and 
Negations in Protein­Protein 
Interactions
in the Biomedical Literature
Using Text Mining




                    
Framework

        HIV­1 and Human Protein­Protein interactions
    


        −   Manually over 7 years
        −   >3000 journal papers
        −   >5000 tuples
        −   Gold standard
        Other negative reports
    


        −   Journal of Negative Results in BioMedicine
        Other gold standards
    


                                     
Detecting Protein­Protein Interactions

        Recognize gene/protein names
    


        −   State of the art ~ 87%
        Identify gene/protein names
    



        Detect the interaction and its qualities
    


        −   70 quot;differentquot; interactions in reference DB




                                      
Protein Name Identification

        1500 human proteins
    


        −   State of the art ~ 87%
        −   Available tools ~ 15%
        −   Our method ~ 35%
        20 HIV proteins
    


        −   No available tool
        −   Our method ~ 95%


                                      
Applications

        Contradictions and            Negations
                                 


        Contrast
        Other diseases                New HIV­1 literature
                                 




                               
Achieved so far & plan for future

        Reproduce the HIV­1 interactions database
    



        Designed an interaction ontology
    



        Identify patterns of negation, contradiction, 
    


        contrast
        Use the above data to increase the annotation 
    


        accuracy



                                 
Evaluation

        Widely used evalutation measures
    


        −   Precision, Recall, F­Score
        −   Sensitivity and Specificity
        Benchmarks and datasets used in challenges
    



        Manually annotated gold standards
    




                                     
Summary



Finding Contradictions, Contrasts and 
Negations in Protein­Protein 
Interactions
in the Biomedical Literature
Using Text Mining

                    

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