title: Phenotypical enrichment strategies for microarray data analysis applied in a type II diabetes study.
abstract: Combining results from gene microarrays, clinical chemistry, and quantitative tissue histomorphology in an integrated bioinformatics setting enables prioritization of gene families as well as individual genes in a type II diabetes animal study. This new methodology takes advantage of a time-controlled mouse study as the animals progress from a normal phenotype to that of type II diabetes. Profiles from different levels of the biological hierarchy of unpooled entities provide an encompassing, system-wide view of biological changes. Here, phenotypic changes on the tissue-structural and physiological level are used as statistical covariants to enrich the gene expression analysis, suggesting correlative processes between gene expression and phenotype unlocked by multi-sample comparisons. We apply correlative and gene set enrichment procedures and compare the results to differential analysis to identify molecular markers. Evaluation based on ontological classifications proves changes in prioritization of disease-related genes that would have been overlooked by conventional gene expression analyses strategies.
authors.affiliation: Icoria, Inc., Pittsburgh, Pennsylvania, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Boyce
authors.forename: Andres
authors.initials: A
authors.lastname: Kriete
authors.forename: Sheila
authors.initials: S
authors.lastname: Nagatomi
authors.forename: Bruce
authors.initials: B
authors.lastname: Kelder
authors.forename: Karen
authors.initials: K
authors.lastname: Coschigano
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002624:Chemistry, Clinical; D019295:Computational Biology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005215:Fasting; D020869:Gene Expression Profiling; D005819:Genetic Markers; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D010641:Phenotype; D012015:Reference Standards
chemical_list: D001786:Blood Glucose; D005819:Genetic Markers; D007328:Insulin