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= Predicting in-vivo SH3 domain mediated protein interactions in human. =

Shobhit Jain, Ruth Isserlin and Gary Bader

== Motivation ==

SH3 domains mediate many intracellular signaling processes and are critical for cell functioning. These domains bind to proline rich regions which can be identified using high-throughput experimental screens such as phage display. SH3 binding motifs identified by phage display can be used to computationally predict domain mediated protein-protein interactions. The existing landscape of computational approaches for predicting protein interactions is either limited by their inability to predict peptide recognition module mediated interactions or do not consider many known constraints governing these interactions.

== Results ==
A novel method of predicting SH3 domain-peptide mediated protein-protein interactions in humans using phage display data is presented. This method builds upon our previously published work of combining multiple binding site and full length protein features using na{\"i}ve Bayesian models for predicting PRM mediated interactions. In this work, we present a novel algorithm for predicting protein interactions using network topology and show that it outperforms the existing approaches. We have also extended the semi-supervised training regime of multinomial na{\"i}ve Bayesian classifier developed for text classification to Gaussian na{\"i}ve Bayesian models for PPI prediction. 

== Downloads ==

==== Latest Release ====
The Domain-Motif Mediated Interaction Prediction (DoMo-Pred) command line tool and all relevant datasets are available under GNU LGPL license from https://github.com/BaderLab/DoMo-Pred-Human or directly download below

Source: [[attachment:DoMo-Pred_human.zip]]

Docker image available at - https://hub.docker.com/r/baderlab/domo-pred-human

==== Predictions ====
[[attachment:SH3_PPI_Predictions_human.zip]]

Text file format:

|| Domain || Peptide || Start || Stop || Sequence || Peptide Score ||  Protein Score ||  Score ||
|| P11710 || P53861  || 313   || 318  || RTTSH    ||      0.96     ||        0.01      ||  0.16 ||
|| P11710 || P34216  ||	236   || 240  || RTTPL    ||      0.53	   ||         0.98       ||  0.98 ||
|| ... || ...  || ...    || ...   || ...    ||...    ||...    ||...    ||

Note: 
  * '''Domain''' is the Uniprot id of SH3 domain containing protein. 
  * '''Peptide''' is the Uniprot id of peptide containing protein. 
  * '''Start and Stop''' are peptide start and stop positions. 
  * '''Sequence''' is the predicted peptide sequence. 
  * '''Peptide Score/Protein Score''' is the score of peptide/protein classifier.  
  * '''Score''' is the score of combined classifier.  

==== Datasets ====
Training and test datasets used in manuscript. 
[[attachment:Datasets_human.zip]]