基因序列的比對是常常被用來比較兩基因的方法，然而有許多應用是需要倚靠兩基因一些生物上的作用，藉此來比較兩基因。對於大部分的基因，其生物上的一些功能，都會以一些生物專有名詞來對該基因加以註解，而在基因本體論上都有定義這些專有名詞的階層關係。因此我們透過研究基因本體論的階層架構並提出計算兩生物專有名詞的語意相似度量測方法，以及基因特徵量化策略來計算兩基因功能上的相近程度，藉此來量化兩基因的功能註解。

　　我們也提供視覺化界面來呈現經過完整計算後相似功能之基因，並且以量化的方式來呈現兩基因在功能上的相近程度，最後利用真實生物路徑配合文獻中作用關係之證據的找尋來發掘未知的生物路徑。

　　Many bioinformatics data resources not only hold data in the form of sequences, but also as annotation. In the majority case, Annotation is written as scientific natural language: this is suitable for humans, but not particularity useful for machine processing. Ontologies offer a mechanism by which knowledge can be represented in a form capable of such processing.

　　In this thesis we investigate the hierarchy of Gene Ontology, and propose a semantic similarity measure for quantifying annotations (Gene Ontology’s terminologies) between two genes. Finally, based on the quantification procedure and finding gene-gene interaction evidences from biomedical literature we try to discover the candidate genes of unknown pathway from well-known pathway.

[1] A. Budanitsky and G. Hirst, “Semantic Distances in WordNet: An Experimental, Application-Oriented Evaluation of Five Measures,” Proceedings of the Workshop WordNet and Other Lexical Resources, Second Meeting North American Chapter Association for Computational Linguistics, Pittsburgh, PA. June 2001.

[2] E. Kretschmann, W. Fleischmann and R. Apweiler “Automatic Rule Generation for Protein Annotation with the C4.5 Data Mining Algorithm Applied on SWISS-PROT,” Bioinformatics, vol. 17, no. 10, pp. 920-926 , 2001.

[3] F.M. Couto, Mario J. Silva and P. Coutinho, “Implementation of Functional Semantic Similarity Measure between Gene-Products,” FCUL Technical Report DI/FCUL TR 3-29, November 2003.

[4] H. Alani, S. Dasmahapatra, K. O’Hara and N. Shadbolt, “Identifying Communities of Practice through Ontology Network Analysis,” IEEE Intelligent System, vol. 18, no. 2, March/April 2003.

[5] J.H. Chiang and H.C. Yu, “MeKE: Discovering the Functions of Gene Products from Biomedical Literature via Sentence Alignment,” Bioinformatics, vol. 19, no. 11, pp. 1417-1422 , 2003.

[6] K.I. Fukuda and T. Takagi, “Knowledge Representation and Signal Transduction Pathways,” Bioinformatics, vol. 17, no.9, pp. 829-837, 2003.

[7] M. McHale, “A Comparison of WordNet and Roget’s Taxonomy for Measuring Semantic Similarity,” Proc. COLING/ACL Workshop on Usage of WordNet in Natural Language Processing Systems, Montreal, Canada, August, pp. 115-120, 1998.

[8] P. Resnik, “Using Information Content to Evaluate Semantic Similarity in a Taxonomy, ” Proceedings of the 14th International Joint Conference on Artificial Intelligence, vol. 1, pp. 448-453, Montreal, August, 1995.

[9] P.W. Lord, R.D. Stevens, A. Brass and C.A. Goble, “Semantic Similarity Measures as tools for exploring the Gene Ontology, ” Pac. Symp. Biocomput. 8, pp. 601-612, 2003.

[10] P.W. Lord, R.D. Stevens, A. Brass and C.A. Goble, “Investigating Semantic Similarity Measures across the Gene Ontology: the Relationship between Sequence and Annotation,” Bioinformatics, vol. 19, no. 10, pp.1275-1283, 2003.

[11] R. Rada, H. Mili, E. Bichnell, and M. Blettner, “Development and Application of a Metric on Semantic Nets,” IEEE Trans. Systems, Man, and Cybernetics, vol. 9, no. 1, pp. 17-30, January 1989.

[12] S.G. Lee, J.U. Hur and Y.S. Kim, “A Graph-Theoretic Modeling on GO Space for Biological Interpretation of Gene Clusters,” Bioinformatics, vol. 20, no. 3, pp. 381-388, 2004.

[13] S. Raychaudhuri and R.B. Altman, “A Literature-Based Method for Assessing Functional Coherence of a Gene Group,” Bioinformatics, vol.19, no. 3, pp. 396-401, 2003.

[14] S. Raychaudhuri, J.T. Chang, P.D. Sutphin, and R.B. Altman, “Associating Genes with Gene Ontology Codes Using a Maximum Entropy Analysis of Biomedical Literature,” Genome Research, 12:203-214, 2001.

[15] T. Ono, H. Hishigaki, A. Tanigami and T. Takagi, “Automated Extraction of Information on Protein-Protein Interactions from the Biological Literature,” Bioinformatics, vol. 17, no. 2, pp. 155-161, 2001.

[16] Y. Li, Z.A. Bandar, and D. McLean, “An Approach for Measuring Semantic Similarity between Words Using Multiple Information Sources”, IEEE Transaction on Knowledge and Data Engineering, vol. 15, no. 4, July/August 2003.

[17] 基因本體論網站：http://www.geneontology.org

[18] LocusLink資料庫網站：http://www.ncbi.nlm.nih.gov/LocusLink/index.html

[19] Biocarta生物路徑網站：http://www.biocarta.com

[20] PubMed網站：http://www.ncbi.nlm.nih.gov/entrez/query.fcgi

[21] 中央研究院計算中心通訊第19卷第20期 <<生物資訊>>