A Tutorial of the PrePPI Database

Presenters: Gabriel Leis and Katrina SherbinaLoyola Marymount University

Departments of Biology and Computer ScienceOctober 3, 2013

Outline

• The PrePPI Database Catalogs Predicted and Experimentally Determined Protein-Protein Interactions

• Overview of the Method to Determine The Probability of Protein-Protein Interactions

• Step-by-Step Tutorial on Using the Database• PrePPI Is a "Meta" Database That is Electronically

Curated• Future Plans to Fix Some of the Problems With the

Current Version of the Database• Conclusion

The PrePPI Database Catalogs Predicted and Experimentally Determined Protein-Protein Interactions• Specific to Homo sapiens and Saccharomyces

cerevisiae• Amino acid sequence of interacting proteins• Functional information about the query protein• Links to experimental evidence for protein interaction• Answers question regarding the

• Likelihood of an interaction • Possible structure of the interacting proteins

Overview of the Method to Determine The Probability of Protein-Protein Interactions

Zhang et al. (2012) Nature 490(7421).

Overview of the Method to Determine The Probability of Protein-Protein Interactions

Zhang et al. (2012) Nature 490(7421).

Outline

• The PrePPI Database Catalogs Predicted and Experimentally Determined Protein-Protein Interactions

• Overview of the Method to Determine The Probability of Protein-Protein Interactions

• Step-by-Step Tutorial on Using the Database• PrePPI Is a "Meta" Database That is Electronically

Curated• Future Plans to Fix Some of the Problems With the

Current Version of the Database• Conclusion

Type In the Protein ID of Interest

The Predicted Interactions Are Displayed In Decreasing Order of Likelihood

… … …

A Likelihood Ratio (LR) Determines How Much the Evidence Contributes to the Predicted PPI

• c1 = S = Structural Model

• c2 = G = GO Term Similarity

• c3 = E = Protein Essentiality (for Yeast)

• c4 = M = MIPS Term Similarity (for Yeast)

• c5 = C = Co-expression

• c6 = P = Phylogenetic Profile Similarityhttp://bhapp.c2b2.columbia.edu/PrePPI/help.html

The Prediction and Database LR are Combined to Get the Final Probability for the Interaction

• Database LR = LR for 1 of 7 categories that an interaction recorded in a database belongs to• Category 1 = Interactions present in multiple databases• Categories 2 – 7 = interactions present in only 1 database

3D Structure of Interacting Proteins Available for Those With A Structural LR > 50

Outline

• The PrePPI Database Catalogs Predicted and Experimentally Determined Protein-Protein Interactions

• Overview of the Method to Determine The Probability of Protein-Protein Interactions

• Step-by-Step Tutorial on Using the Database• PrePPI Is a "Meta" Database That is

Electronically Curated• Future Plans to Fix Some of the Problems With

the Current Version of the Database• Conclusion

PrePPI Is a "Meta" Database That is Electronically Curated

• Developed by the Honig Lab (Columbia University and HHMI)

• Funding from NIH and China Scholarship Council• Licenses available for commercial and academic

institutions• Latest version released 1/27/2012

Future Plans to Fix Some of the Problems With the Current Version of the Database

• Problems• No evaluation of structure beyond the final LR score• No attention paid to oligomerization state• No differentiation between compartmental paralogs

• Future Plans• Implement methods to create more reliable structures• Expand to other model organisms

Conclusion

• The PrePPI database catalogs protein-protein interactions both predicted and experimentally determined

• Likelihood ratios (LR) are computed to determine how probable is a predicted interaction

• A potential 3D representation of the interacting proteins is available for those interactions with an LR>50

• PrePPI is a “meta" database that is electronically curated

• Future plans include expanding the database to include more organisms and developing methods to create more reliable interaction structures

References

• Zhang et al. (2012). Structure-based prediction of protein–protein interactions on a genome-wide scale. Nature, 490(7421), 556-560. Retrieved from http://www.nature.com/nature/journal/v490/n7421/full/nature11503.html

• Zhang et al. (2013). PrePPI: a structure-informed database of protein-protein interactions. Nucleic Acids Research, 41, 828-833. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531098/

• Zhang et al. (Designer). (2012, October 25). Predicting protein–protein interactions using PrePPI [Web Graphic]. Retrieved from http://www.nature.com/nature/journal/v490/n7421/fig_tab/nature11503_F1.html