Aligning Ontologies and Integrating Textual Evidence for Pathway Analysis of Microarray Data

摘要

Expression arrays are introducing a paradigmatic change in biology by shifting experimental approaches from single gene studies to genome-level analysis, monitoring the expression levels of several thousands of genes in parallel. The massive amounts of data obtained from the microarray data needs to be integrated and interpreted to infer biological meaning within the context of information-rich pathways. In this paper, we present a methodology that integrates textual information with annotations from cross-referenced ontologies to map genes to pathways in a semi-automated way. We illustrate this approach and compare it favorably to other tools by analyzing the gene expression changes underlying the biological phenomena related to stroke. Stroke is the third leading cause of death and a major disabler in the United States. Through years of study, researchers have amassed a significant knowledge base about stroke, and this knowledge, coupled with new technologies, is providing a wealth of new scientific opportunities. The potential for neuroprotective stroke therapy is enormous. However, the roles of neurogenesis, angiogenesis, and other proliferative responses in the recovery process following ischemia and the molecular mechanisms that lead to these processes still need to be uncovered. Improved annotation of genomic and proteomic data, including annotation of pathways in which genes and proteins are involved, is required to facilitate their interpretation and clinical application.