Protein Complex Prediction

Participants: Hon Nian Chua, Joanne Lee, Kevin Lim, Guimei Liu, Iana Pyrogova, Limsoon Wong, Chern Han Yong

Background

Progress in high-throughput experimental techniques in the past decade has resulted in a rapid accumulation of protein-protein interaction (PPI) data. However, recent surveys reveal that interaction data obtained by the popular high-throughput assays such as yeast-two-hybrid experiments may contain as much as 50% false positives and false negatives. As a result, further carefully-focused small-scale experiments are often needed to complement the large-scale methods to validate the detected interactions. However, the vast interactomes require much more scalable and inexpensive approaches. Thus it would be useful if the list of protein-protein interactions detected by such high-throughput assays could be prioritized in some way.

Furthermore, the PPI networks resulting from these assays are still essentially an in vitro scaffold. Further progress in computational analyses techniques and experimental methods is needed to reliably deduce in vivo protein interactions, to distinguish between permanent and transient interactions, to distinguish between direct protein binding from membership in the same protein complex and to distinguish protein complexes from functional modules.

Objectives

In a past project, we studied techniques for assessing the reliability of PPIs. In this project, we aim to advance computational techniques for:

Assessing the reliability of PPIs detected by high-throughput methods;
Deriving protein complexes from PPI networks; and
Exploring approaches for distinguishing the various forms of interactions mentioned above.

At the end of the project, we expect to have developed a robust and powerful system to postprocessing results of high-throughput PPI assays, as well as integrating extensive annotation information, yielding a more informative protein interactome beyond a mere in vitro scaffold.

Selected Publications

Jin Chen, Hon Nian Chua, Wynne Hsu, Mong-Li Lee, See-Kiong Ng, Rintaro Saito, Wing-Kin Sung, Limsoon Wong. Increasing Confidence of Protein-Protein Interactomes. Proceedings of 17th International Conference on Genome Informatics (GIW), pages 284--297, Yokohama, Japan, 18-20 December 2006. (invited keynote paper) PDF, FSWeight V2.1 Software
Hon Nian Chua, Kang Ning, Wing-Kin Sung, Hon Wai Leong, Limsoon Wong. Using Indirect Protein-Protein Interactions for Protein Complex Prediction. Proceedings of 6th Annual International Conference on Computational Systems Bioinformatics (CSB), pages 97--110, San Diego, California, August 2007. PDF, PCP V1.0 Software
Hon Nian Chua, Kang Ning, Wing-Kin Sung, Hon Wai Leong, Limsoon Wong. Using Indirect Protein-Protein Interactions for Protein Complex Prediction. Journal of Bioinformatics and Computational Biology, 6(3):435--466, June 2008. PDF, PCP V1.0 Software
Hon Nian Chua, Limsoon Wong. Increasing the Reliability of Protein Interactomes. Drug Discovery Today, 13(15/16):652--658, August 2008. PDF
Hon Nian Chua, Willy Hugo, Guimei Liu, Xiaoli Li, Limsoon Wong, See-Kiong Ng. A Probabilistic Graph-Theoretic Approach to Integrate Multiple Predictions for the Protein-Protein Subnetwork Prediction Challenge. Annals of New York Academy of Sciences, 1158:224-233, March 2009. PDF
Wilson Goh, Hirotaka Oikawa, Judy Sng, Marek Sergot, Limsoon Wong. The role of miRNAs in complex formation and control. Bioinformatics, 28(4):453--456, February 2012. PDF
Mahnaz Habibi, Changiz Eslahchi, Limsoon Wong. Protein Complex Prediction based on k-Connected Subgraphs in Protein Interaction Network. BMC Systems Biology, 4:129, September 2010. PDF
Guimei Liu, Jinyan Li, Limsoon Wong. Assessing and Predicting Protein Interactions Using Both Local and Global Network Topological Metrics. Proceedings of 19th International Conference on Genome Informatics (GIW), pages 138--149, Gold Coast, Australia, 3 December 2008. PDF, PPT
Guimei Liu, Limsoon Wong, Hon Nian Chua. Complex Discovery from Weighted PPI Networks. Bioinformatics, 25(15):1891--1897, August 2009. PDF, CMC Software
Guimei Liu, Chern Han Yong, Hon Nian Chua, Limsoon Wong. Decomposing PPI Networks for Complex Discovery. Proceedings of 4th IEEE International Conference on Bioinformatics & Biomedicine, pages 280--283, Hong Kong, December 2010. PDF
Guimei Liu, Chern Han Yong, Hon Nian Chua, Limsoon Wong. Decomposing PPI Networks for Complex Discovery. Proteome Science, 9(Suppl. 1):S15, October 2011. PDF
Alireza Vazifedoost, Maseud Rahgozar, Behzad Moshiri, Mehdi Sadeghi, Hon Nian Chua, See Kiong Ng, Limsoon Wong. Using data fusion for scoring reliability of protein-protein interactions. Journal of Bioinformatics and Computational Biology, 12(4):1450014, August 2014. PDF
Limsoon Wong, Guimei Liu. Protein Interactome Analysis for Countering Pathogen Drug Resistance. Journal of Computer Science and Technology, 25(1):124--130, January 2010. PDF
Min Wu, Xiaoli Li, Chee-Keong Kwoh, See-Kiong Ng, Limsoon Wong. Discovery of Protein Complexes with Core-Attachment Structures from TAP Data. Journal of Computational Biology, 19(9):1027--1042, September 2012.
Chern Han Yong, Guimei Liu, Hon Nian Chua, Limsoon Wong. Supervised maximum-likelihood weighting of composite protein networks for complex prediction. BMC Systems Biology, 6(Suppl 2):S13, December 2012. PDF, SWC Software
Chern Han Yong, Osamu Maruyama, Limsoon Wong. Discovery of small protein complexes from PPI networks with size-specific supervised weighting. BMC Systems Biology, 8(Suppl 5):S3, December 2014. PDF, SSS Software
Chern Han Yong, Limsoon Wong. From the static interactome to dynamic protein complexes: Three challenges. Journal of Bioinformatics and Computational Biology, 13(2):1571001, April 2015. PDF
Chern Han Yong, Limsoon Wong. Prediction of problematic complexes from PPI networks: Sparse, embedded, and small complexes. Biology Direct, 10:40, August 2015. PDF, IntegratedComplexPrediction Software
Sriganesh Srihari, Chern Han Yong, Ashwini Patil, Limsoon Wong. Methods for protein complex prediction and their contributions towards understanding the organization, function and dynamics of complexes. FEBS Letters, 589(19):2590--2602, September 2015.
Sriganesh Srihari, Jitin Singla, Limsoon Wong, Mark Ragan. Inferring synthetic lethal interactions from mutual exclusivity of genetic events in cancer. Biology Direct, 10:57, October 2015. PDF
Osamu Maruyama, Limsoon Wong. Regularizing predicted complexes by mutually exclusive protein-protein interactions. Proceedings of IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining, pages 1068--1075, Paris, 25-28 August 2015. PDF
Sriganesh Srihari, Chern Han Yong, Limsoon Wong. Computational Prediction of Protein Complexes from Protein Interaction Networks, Morgan & Claypool Publishers, San Rafael, CA, July 2017. (281 pages)
Iana Pyrogova, Limsoon Wong. Protein complex prediction by date-hub removal. Computational Biology and Chemistry, 74:407--419, June 2018. PPT

Dissertations

Hon Nian Chua, Graph-based methods for protein function prediction. PhD thesis, Graduate School Integrative Sciences and Engineering, National University of Singapore, Singapore, 2007.
Chern Han Yong, Discovering dynamic protein complexes from static interactomes: Three challenges. PhD thesis, Graduate School Integrative Sciences and Engineering, National University of Singapore, Singapore, 2015.
Iana Pyrogova, Protein complex prediction by date-hub removal. MSc thesis, School of Computing, National University of Singapore, Singapore, 2017.
Junliang Kevin Lim, Inferring Protein Function Module from Protein Interaction Information. Final Year Project Report, School of Computing, National University of Singapore, Singapore, 2009.
Yu Ling Joanne Lee, Protein Complex Inference Enhanced by Text Mining. Final Year Project Report, School of Computing, National University of Singapore, Singapore, 2010.
Yu Bai, Recognizing Small Protein Complexes from Protein Interaction Network, Final Year Project Report, School of Computing, National University of Singapore, 2013.

Selected Presentations

Guimei Liu. An Iterative Approach to Weighting and Expanding Protein Interaction Networks and its Impact on Complex Discovery. Invited talk at IMS Workshop on Computational Systems Biology Approaches to Analysis of Genome Complexity and Regulatory Gene Networks, Institute for Mathematical Sciences, NUS, Singapore, 20-25 November 2008. PPT
Limsoon Wong. Increasing Confidence of Protein-Protein Inteactomes. Keynote talk at 17th International Conference on Genome Informatics, Yokohama, Japan, 18-20 December 2006. PPT
Limsoon Wong. Increasing Confidence of Protein-Protein Interactomes. Invited tutorial at Computational Methods in Biomolecular Structures and Interaction Networks Program, Institute for Mathematical Sciences, Singapore, 13 July 2007. PPT
Limsoon Wong. Constructing More Reliable Protein-Protein Interaction Maps. Invited talk at Bioinformatica Indica '08: International Symposium on Computational Biology & Bioinformatics, University of Kerala, 17-19 January 2008. PDF, PPT
Limsoon Wong. Increasing Confidence of Protein-Protein Interactomes. Invited talk at IPM-NUS Workshop on Analysis and Application of Protein Interaction Networks, Shahid Beheshti University, Tehran, Iran, 17-18 November 2008. PPT
Limsoon Wong. Identifying Protein Complexes from Protein Interactome Maps. Invited talk at IPM-NUS Workshop on Analysis and Application of Protein Interaction Networks, Shahid Beheshti University, Tehran, Iran, 17-18 November 2008. PPT
Limsoon Wong. Guilt by Association of Common Interaction Partners. Invited talk at IPM-NUS Workshop on Analysis and Application of Protein Interaction Networks, Shahid Beheshti University, Tehran, Iran, 17-18 November 2008. PPT
Limsoon Wong. Identifying Protein Complexes from Protein Interactome Maps. Invited talk at Joint 5th Structural Biology & Functional Genomics and 1st Biological Physics International Conference, University of Cultural Centre, NUS, Singapore, 9-11 December 2008.
Limsoon Wong. Identifying Protein Complexes from Protein Interactome Maps. Invited Keynote at 8th Korea-Singapore Joint Workshop on Bioinformatics and NLP, KAIST, Daejeon, Korea, 15 December 2008.
Limsoon Wong. Identifying Protein Complexes from Protein Interactome Maps. Invited keynote at IEEE International Workshop on Data Mining and Artificial Intelligence (DMAI 2008), Khulna, Bangladesh, 25-27 December 2008. PPT
Limsoon Wong. Identifying Protein Complexes from Protein Interactome Maps. Invited talk at ASI Symposium on Bioinformatics and Data Mining, Hong Kong Baptist University, 26-27 February 2009.
Limsoon Wong. Identifying Protein Complexes from Protein Interactome Maps. Invited talk at International Conference on Open Source for Computer Aided Drug Discuvery (OSCADD 2009), IMTECH, Chandigarh, India, 22-26 March 2009. PPT
Limsoon Wong. Topology of PPI Networks: Applications and Questions. Talk at Barbados Workshop on Biological and Computational Analysis of Protein-Protein Interaction Networks, Bellairs Research Institute, Barbados, 19-25 April 2009. PPT
Limsoon Wong. Challenges in Understanding Pathways, Predicting Complexes, & Inferring Protein Function. Invited keynote at First International Workshop on Neuroinformatics, Bioinformatics, and Cognitive Science, South China University of Technology, Guangzhou, China, 4-6 June 2009. PPT
Limsoon Wong. Topology of PPI Networks: Applications and Questions. Invited talk at Shanghai Center for Bioinformation Technology, Shanghai, China, 24 July 2009.
Limsoon Wong. Topology of PPI Networks: Applications and Questions. Invited talk at University of Warsaw, Warsaw, Poland, 13 January 2010. PPT
Limsoon Wong. Recent Progress in Protein Complex Prediction from PPI Networks. Invited talk at Chinese University of Hong Kong, Hong Kong, 29 March 2010.
Limsoon Wong. The impact of microRNAs on the organization of protein interactions and formation of protein complexes Invited talk at CSHA Conference on Computational Biology, Suzhou, China, 29 September 2010. PPT
Limsoon Wong. Impact on MicroRNAs on Organization of Protein Interactions and Formation of Protein Complexes. Invited Talk at 2nd IPM-NUS Workshop on Computational Biology, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran, 6 April 2011.
Limsoon Wong. Protein complex prediction from PPIN. Invited talk at SNU Bioinformatics Workshop and Biofestival 2013, Seoul National University, Seoul, Korea, 23 May 2013. PPT
Limsoon Wong. Big data in bioinformatics: Is more better?. Invited talk at KAUST CBRC Inauguration Symposium, Thuwal, Saudi Arabia, 8 June 2014. PPT
Limsoon Wong. Progress on three challenges in predicting dynamic protein complexes from a static protetin interactome. Invited talk at University of Tehran, Tehran, Iran, 11 March 2015. PPT

Acknowledgements

This project is supported in part by two A*STAR AGS scholarships (Chua: 8/03 - 7/07, Yong: 1/09 - ), a URC grant R-252-000-274-112 (Liu, Wong: 10/06 - 9/09), and a NRF CRP grant NRF-G-CRP-2997-04-082(d) (Wong: 4/08 - 3/13).

Last updated: 14/6/2018, Limsoon Wong.