Enabling More Sophisticated Analysis of Gene Expression and Proteomic Profiles for Understanding Diseases and Optimizing Treatments

Participants: Difeng Dong, Donny Soh, Wilson Goh, Jingjing Jin, Chuan Hock Koh, Limsoon Wong

Background

We survey the progress in the analysis of gene expression and proteomic profiling data for the purposes of disease subtype diagnosis, new subtype discovery, and understanding of diseases and treatment responses. We find existing works fall short on several issues: these works provide little information on the interplay between selected genes and proteins; the collection of pathways that can be used, evaluated, and ranked against the observed expression data is limited; and a comprehensive set of rules for reasoning about relevant molecular events has not been compiled and formalized.

Objectives

We thus envision an advanced integrated framework, and are developing a system based on it, to provide biologically inspired solutions. It comprises:

Automated analysis and extraction of information from biomedical texts;
Targeted construction of known pathways; and
Direct hypothesis generation based on logical reasoning on, and tests for, consistencies and inconsistencies of observed data against known pathways.

Selected Publications

Guimei Liu, Jinyan Li, Kelvin Sin, Limsoon Wong. Distance-Based Subspace Clustering with Flexible Dimension Partitioning. Proceedings of 23rd IEEE International Conference on Data Engineering, pages 1250--1254, Istanbul, Turkey, April 2007 PDF, nClusters Software, V1.0
Donny Soh, Difeng Dong, Yike Guo, Limsoon Wong. Enabling More Sophisticated Gene Expression Analysis for Understanding Diseases and Optimizing Treatments. ACM SIGKDD Explorations, 9(1):3--14, June 2007. PDF
Wen-Son Hsieh, Ross Soo, Bee-Keow Peh, Thomas Loh, Difeng Dong, Donny Soh, Limsoon Wong, Simon Green, Judy Chiao, Chun-Ying Cui, Yoke-Fong Lai, Soo-Chin Lee, Benjamin Mow, Richie Soong, Manuel Salto-Tellez, Boon-Cher Goh. Pharmacodynamic Effects of Seliciclib, an Orally Administered Cell Cycle Modulator, in Undifferentiated Nasopharyngeal Cancer. Clinical Cancer Research, 15(4):1435--1442, February 2009. PDF
Difeng Dong, Chun-Ying Cui, Benjamin Mow, Limsoon Wong. Deciphering Drug Action and Escape Pathways: An Example on Nasopharyngeal Carcinoma. Proceedings of 1st International Conference on Bioinformatics and Computational Biology (BICOB2009), pages 199--210, New Orleans, USA, 8-10 April 2009. PDF, Drug Pathway Decipherer V1.0 (Nov 2007), Drug Pathway Decipherer V2.0 (Dec 2008)
Guimei Liu, Kelvin Sim, Jinyan Li, Limsoon Wong. Efficient Mining of Distance-Based Subspace Clusters. Statistical Analysis and Data Mining, 2(5):427--444, December 2009. nClusters Software, V1.1
Rajesh Chowdhary, Vladimir B. Bajic, Difeng Dong, Limsoon Wong, Jun S. Liu. Genome-wide analysis of regions similar to promoters of histone genes. BMC Systems Biology, 4(Suppl 1):S4, May 2010. PDF
Chuan Hock Koh, Masao Nagasaki, Ayumu Saito, Limsoon Wong, Satoru Miyano. DA 1.0: Parameter Estimation of Biological Pathways Using Data Assimilation Approach. Bioinformatics, 26(14):1794--1796, July 2010. PDF. DA 1.0 Software.
Donny Soh, Difeng Dong, Yike Guo, Limsoon Wong. Consistency, Comprehensiveness, and Compatibility of Pathway Databases. BMC Bioinformatics, 11:449, September 2010. PDF, Supplementary Data, PathwayAPI Online.
Thomas Thamboo, Richie Soong, Limsoon Wong, Baidah Ahmad, Yaw-Chyn Lim, Ming Teh. Determination of a molecular signature of acute T-cell-mediated renal allograft rejection using quantitative real-time RT-PCR of 45 genes on a low density array. Pathology, 43(1):72--75, January 2011.
Wen Lee Tan, Bhaskar Bhattacharya, Marie Chiew Hsia Loh, Indirikumar Balasubramanian, Mohamed Akram, Difeng Dong, Limsoon Wong, Bhavin Thakkar, Manuel Salto-Tellez, Ross Soo, Iduna Fichtner, Barry Iacopetta, Richie Soong. Low cytosine triphosphate synthase 2 expression renders resistance to 5-fluorouracil in colorectal cancer. Cancer Biology & Therapy, 11(6):599--608, March 2011.
Chuan Hock Koh, Masao Nagasaki, Ayumu Saito, Chen Li, Limsoon Wong, Satoru Miyano. MIRACH: Efficient Model Checker for Quantitative Biological Pathway Models. Bioinformatics, 27(5):734-735, March 2011. PDF. MIRACH Software
Limsoon Wong. Using Biological Networks in Protein Function Prediction and Gene Expression Analysis. Internet Mathematics, 7(4):274--298, December 2011. PDF.
Wilson Goh, Yie Hou Lee, Ramdzan Zubaidah, Jingjing Jin, Difeng Dong, Qingsong Lin, Maxey Chung, Limsoon Wong. A Network-based pipeline for analyzing MS data---An application towards liver cancer. Journal of Proteome Research, 10(5):2261--2272, May 2011.
Donny Soh, Difeng Dong, Yike Guo, Limsoon Wong. Finding Consistent Disease Subnetworks Across Microarray Datasets. BMC Genomics, 12(Suppl. 13):S15, November 2011. PDF, Supplementary Data
Wilson Goh, Yie Hou Lee, Zubaidah Ramdzan, Marek Sergot, Maxey Chung, Limsoon Wong. Proteomics Signature Profiling (PSP): A novel contextualization approach for cancer proteomics. Journal of Proteome Research, accepted.

Dissertations

Donny Soh. Understanding Pathways. PhD thesis, Department of Computing, Imperial College London, UK, 2009.
Difeng Dong. Relapse Prediction in Childhood Acute Lymphoblastic Leukemia by Time-Series Gene Expression Profiling. PhD thesis, School of Computing, National University of Singapore, 2011.

Selected Presentations

Limsoon Wong. Two Applications of Text Mining in Bioinformatics: Enhancing Protein Function Prediction and Enhancing Drug Pathway Inference. Invited talk at 7th Korea-Singapore Workshop on Bioinformatics & NLP, Seoul, Korea, 15 February 2008. PPT
Difeng Dong, Guimei Liu, Limsoon Wong. Drug Pathway Decipherer and Some Exciting Results in Protein Complex Prediction. Invited talk at Symposium on Biomolecular Mechanism Discovery with Computational Biology, Biopolis, Singapore, 14 August 2008. 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. Some of My Headaches in Gene Expression Analysis. Invited talk at Dept of Pediatrics, NUH, Singapore, 14 October 2009.
Limsoon Wong. Consistency and Comprehensiveness of Pathway Databases. Invited talk at 9th Korea-Singapore Workshop on Bioinformatics and NLP, KAIST, Daejeon, Korea, 23 February 2010. PPT
Limsoon Wong. Finding Consistent Disease Subnetworks. Invited talk at HKUST, Hong Kong, 26 March 2010. PPT
Limsoon Wong. Enabling Reproducible Gene Expression Analysis. International Outstanding Scientist Series, Key Laboratory of Systems Biology, SIBS, CAS, Shanghai, China, 26 February 2011.
Limsoon Wong. Enabling Reproducible Gene Expression Analysis Using Biological Pathways. Invited talk at 2nd IPM-NUS Workshop on Computational Biology, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran, 6 April 2011.
Limsoon Wong. Enabling Reproducible Gene Expression Analysis. Invited talk at 5th Moscow Conference on Computational Molecular Biology (MCCMB), Moscow State University, Moscow, Russia, 24 July 2011. PPT
Limsoon Wong. Delivering Reproducible Gene Expression Analysis. Invited lecture for Microarray Workshop on Gene Expression Analysis for Aspiring Clinician Researchers, Clinical Research Centre, NUS, 23 September 2011. PPT
Limsoon Wong. A Novel Principle for Childhood ALL Relapse Prediction. Invited talk at 10th Korea-Singapore Workshop on Bioinformatics and NLP (KSW), Daegeon, South Korea, 12 December 2011. PPT
Limsoon Wong. A Novel Principle for Childhood ALL Relapse Prediction. Invited talk at UTS AAI Bioinformatics Workshop 2012, University of Technology Sydney, NSW, Australia, 12 January 2012. PPT
Limsoon Wong. Analysis of Gene Expression and Proteomic Profiles based on Biological Networks. Tutorial at 10th Asia Pacific Bioinformatics Conference (APBC2012), Melbourne, Australia, 17-19 January 2012. PPT, Written notes
Limsoon Wong. Using Biological Networks for Protein Function Prediction, Biomarker Identification, and Other Problems in Computational Biology. Invited master class at 2012 International Winter School in Methods in Bioinformatics (WSMBio 2012), Tarragona, Spain, 20-24 February 2012. PPT

Acknowledgements

This project is supported in part by NUS ARF grant R-252-050-238-101/133 (Wong: 11/05 - 11/08), NUS URC grant R-252-000-274-112 (Wong: 10/06 - 09/09, Dong: 12/08 - 09/09), SERC PSF grant 072 101 0016 (Wong: 8/07 - 7/10, Soh: 1/09 - 12/09), NRF CRP grant NRF-G-CRP-2997-04-082(d) (Wong: 4/08 - 3/13, Dong: 10/09 - 12/10), MOE Tier-2 grant MOE2009-T2-2-004 (Wong, Goh, Jin: 4/10 - 3/13), an NUS NGS scholarship (Koh: 09/08 - 08/12), and an A*STAR AIP scholarship (Soh: 12/04 - 12/08).

Last updated: 14/1/12, Limsoon Wong.