Chen-Hsiang Yeang

Simons Center for Systems Biology

Institute for Advanced Study

1 Einstein Drive, Princeton, NJ 08540

E-mail: chyeang@ias.edu

I am currently a member of the Simons Center for Systems Biology at the Institute for Advanced Study in Princeton. My research interests focus on three topics in computational biology: 1) Understanding the cross-talks of major signaling and regulatory pathways in cancer, 2) Studying the coupled evolution between components in biomolecular systems, 3) Integrating multiple sources of information to reconstruct the networks of gene regulation and their coupling with other systems, and suggesting new experiments to validate or disambiguate inferred models. Specifically, by examining the data of somatic mutations in cancer, we found that the same set of signaling pathways exhibit qualitatively different couplings in different tumor tissues (FASEB J. 2008). We built a computational model that identifies coevolving nucleic or amino acids from aligned sequences of multiple species. This model can capture different types of interactions (RNA-RNA, amino acid-amino acid, etc.), incorporates phylogenetic information, and requires very few extra free parameters. Using this model, we successfully detected RNA secondary and tertiary interactions (Mol. Biol. Evol. 2007) and established a compendium of coevolving positions among all the known protein domains (PLoS Comp. Biol. 2007). We developed a modeling framework to integrate the data of protein-protein, protein-DNA interactions and knock-out gene expression to identify the “active pathways” that may propagate the knock-out effects to downstream genes (JCB 2004), and validated the pathway models by new knock-out experiments suggested by an information theoretic criterion (Genome Biol. 2005). We further extended this modeling framework to capture the combinatorial regulation of multiple transcription factors (JCB 2006) and the coupling between gene regulation and metabolic reactions (BMC Bioinformatics 2006).

 

Selected Publications

Journal Articles

C.H. Yeang, F. McCormick, A. Levine. Combinatorial patterns of somatic gene mutations in cancer. The FASEB Journal 22:2605-2622, 2008. [pdf], [pubmed link].

C.H. Yeang. Identifying coevolving partners from paralogous gene families. Evolutionary Bioinformatics 4:91-107, 2008. [pdf].

C.H. Yeang, D. Haussler. Detecting coevolution in and among protein domains. PLoS Computational Biology 3(11):e211, 2007. [pdf], [pubmed link].

C.H. Yeang, J.F.J. Darot, H.F. Noller, D. Haussler. Detecting the coevolution of biosequences – an example of RNA interaction prediction. Molecular Biology and Evolution 24(9):2119-2131, 2007. [pdf], [errata], [pubmed link].

C.H. Yeang, M. Vingron.  A joint model of regulatory and metabolic networks.  BMC Bioinformatics 7:332 2006.   [pdf], [pubmed link].

C.H. Yeang, T. Jaakkola. Modeling the combinatorial functions of multiple transcription factors. Journal of Computational Biology (JCB), 13(2): 463-480, 2006. [pdf], [pubmed link].

C.H. Yeang, C. Mak, C. Workman, S. McCuine, T. Jaakkola, T. Ideker.  Validation and refinement of gene-regulatory pathways on a network of physical interactions.  Genome Biology 6:R62.1-R62.10, 2005.   [pdf], [pubmed link].

C.H. Yeang, T. Ideker, T Jaakkola.  Physical network models.  Journal of Computational Biology (JCB), 11(2-3): 243-262, 2004.  [pdf], [pubmed link].

S. Ramaswamy et al. Multiclass cancer diagnosis using tumor gene expression signatures.  Proceedings of National Academy of Science U.S.A. (PNAS) 98:15149-15154, 2001.  [pdf], [pubmed link].

Peer-reviewed Conference Papers 

L. Perez-Breva, L.E. Ortiz, C.H. Yeang, T. Jaakkola.  Game theoretic algorithms for protein-DNA binding.  Proceedings, the 12th Annual Conference on Neural Information Processing (NIPS), Vancouver, Canada, 2006. [pdf].

J. Darot, C.H. Yeang, D. Haussler.  Detecting the dependent evolution of biosequences.  Proceedings, the 10th Annual International Conference of the Research in Computational Molecular Biology (RECOMB), Venice, Italy, 2006.  [pdf].

C.H. Yeang and T. Jaakkola.  Modeling the combinatorial functions of multiple transcription factors.  Proceedings, the 9th Annual International Conference of the Research in Computational Molecular Biology (RECOMB), Boston, Massachusetts, U.S.A., 2005.  [pdf].

C.H. Yeang and M. Szummer. Continuous Markov random walks.  Proceedings, the 18th conference of uncertainty in artificial intelligence (UAI), Acapulco, Mexico, 2003.  [pdf].

C.H. Yeang and T. Jaakkola, Physical network models and multi-source data integration.  Proceedings, the 7th conference on research in computational biology (RECOMB), Berlin, Germany, 2003.  [pdf].

C.H. Yeang and T. Jaakkola.  Time-series analysis of gene expression and location data.  Proceedings, the 3rd IEEE conference on bioinformatics and bioengineering (BIBE), Bethesda, Maryland, U.S.A., 2003.  [pdf].

C.H. Yeang.  An information geometric perspective on active learning.  Proceedings, the 13th European conference on machine learning (ECML), Helsinki, Finland, 2002.  [pdf].

C.H. Yeang et al. Molecular classification of multiple tumor types.  Proceedings, the 9th conference on intelligent systems for molecular biology (ISMB), Copenhagen, Denmark, 2001.  [pdf], [pubmed link].

Thesis

Inferring regulatory networks from multiple sources of genomic data.  Sc. D. Thesis.  Supervisor: Tommi Jaakkola.  Massachusetts Institute of Technology, 2004.  [pdf].

 

Downloadable Software and Source Codes

Coevolutionary Continuous-Time Markove Process Model (PLoS Comp. Biol. 2007; Mol. Biol. Evol. 2007).

Physical Network Model (JCB 2004; Genome Biol. 2005). The Java plug-in of Cytoscape (written by Craig Mak at Trey Ideker's group) is also available at the supplementary website of the Genome Biology paper.

 

Curriculum Vitae

 

Past and Current Collaborators

Arnold Levine, Simons Center for Systems Biology, Institute for Advanced Study.

David Haussler, Center for Molecular Science and Engineering, UC Santa Cruz.

Josh Stuart, Department of Biomolecular Engineering, UC Santa Cruz.

Harry Noller, Center for Molecular Biology of RNA, UC Santa Cruz.

Tommi Jaakkola, Electrical Engineering and Computer Science Department, MIT.

Trey Ideker, Department of Bioengineering, UC San Diego.

Martin Vingron, Max-Planck Institute for Molecular Genetics.

 

Student Collaborators

Charlie Vaske, Department of Biomolecular Engineering, UC Santa Cruz.

Pinal Kanabar, Department of Biomolecular Engineering, UC Santa Cruz.

Jeremy Darot, European Bioinformatics Institute.