Glycome Informatics for the Practical Application of Computational Models Kiyoko F. Aoki-Kinoshita Dept. of Bioinformatics, Soka University (formerly of Bioinformatics Center@Kyoto University) Frontiers in Glycomics: Bioinformatics and Biomarkers in Disease September 11-13, 2005

Another vocabulary term Glycome Informatics Algorithms, methods and computational models for the study of the glycome (Glycome: the repertoire of glycans in a cell, tissue, or organism)

Informatics Techniques for Glycomics Mass spec prediction/annotation StrOligo (M. Ethier et al, Methods Mol Biol., 2006) Cartoonist (D. Goldberg et al, Proteomics, 2005) H. Tang et al, Bioinformatics, 2005 Method using glycan arrays Structure prediction from glycosyltransferase expression data (S. Kawano et al, Bioinformatics, 2005)

Algorithmic Techniques for Glycome Informatics Computer Theoretic Algorithms for Trees KCaM: K.F. Aoki et al, NAR, 2004 Score matrix for glycan linkages, K.F. Aoki et al, Bioinformatics, 2005 Least common supertree approximation algorithm for reconstructing glycans from spectral data, K.F. Aoki-Kinoshita et al, ISAAC 2006 Probabilistic Models PSTMM, N. Ueda et al, TKDE, 2005 Profile PSTMM, K.F. Aoki-Kinoshita et al, ISMB 2006 OTMM, Hashimoto et al, KDD 2006 Kernel Methods Leukemia marker detection, Y. Hizukuri et al, Carbohydrate Research, 2005 General purpose marker detection, T. Kuboyama et al, GIW 2006 (submitted) Proteins Glycans Smith-Waterman KCaM PAM/ BLOSUM Glycan Score Matrix (Profile) HMM (Profile) PSTMM

Applications of Probabilistic Models Statistically compute the common patterns in tree structures Profile PSTMM (Probabilistic Sibling-dependent Tree Markov Model) Provided binding affinity data for a specific lectin, compute the most likely structure being recognized Statistically compute the key patterns of sulfation in GAGs based on various biological measurements (i.e. inhibition)

Kernel Methods Machine learning method http://www-kairo.csce.kyushu-u.ac.jp/~norikazu/research.en.html Machine learning method e.g. Support Vector Machines (SVM) Can handle features in high-dimensions e.g. Expression data, pathway information, localization information, etc. Statistically computes commonalities by reducing the dimensions of the data Data classification Feature extraction

Leukemia-specific features Hizukuri et al, Carbohydr. Res. 340, 2270-2278 (2005). Used KEGG GLYCAN data: Entries whose CarbBank annotations were related to leukemic cells, erythrocytes, plasma and serum Predicted possible glycan markers Correlated well with experimental data

Glyco-Databases & Resources：the Vision XML XML XML XML XML Bacterial Carbohydrate Structure DataBase

Resource for Glycome Informatics at Soka (RINGS) Goal: a publicly available web resource of tools for glycome analysis Started April, 2006 Currently based on KEGG GLYCAN, REACTION, ENZYME data Glycan structures Glycan interaction information Links proteins to related glycans 3D protein data from PDB Currently available tools: BLAST Server for nucleotide and protein sequences 2D Drawing Tool written in Java for queries Glycan structure estimation from microarray expression data

DrawRINGS 2D glycan structure drawing tool Can also query the RINGS database and retrieve similar structures Resulting Glycan IDs are linked to corresponding entry pages Each Interaction that the resulting glycans are involved in are also listed

BLAST Search Glycan-related proteins can be searched for by sequence using BLAST

3D Protein Structures

RINGS Microarray Tool Based on method of S. Kawano et al., Bioinformatics, 2005 Input: Glycosidic bonds and values Corresponding to glycosyltransferase expression data Output: Glycan structures and related interaction information

RINGS Microarray Tool

Ongoing Work Implementation of more free web-based tools for analysis Careful incorporation of other data is planned Glycosciences, CFG, BCSDB, etc. MSn data... But...

For the Community What tools are currently lacking? Web Portal Glycosciences.de has links to many resources Search of multiple resources from a single query interface By structure By protein By disease Or combo of the above Web-based MS analysis tool Open to suggestions/requests http://rings.t.soka.ac.jp Email: kkiyoko@t.soka.ac.jp

Acknowledgements Masao Ichikawa, Shuichi Ikeda, Kouichi Yamada, Takako Yamaguchi NIH