This has been applied recently for the identification of pathways altered upon
differentiation of inner cell mass and trophectoderm in the human blastocyst47 and upon hormoneinduced aging of the human skin.48 The procedure is based on pathway annotation (for example provided by the Kyoto Encyclopedia of Genes and Genomes [KEGG] pathway database).49 This information is then translated into a two-dimensional statistical test problem that involves Wilcoxon’s signed rank sum test in order to compute a Z-score for each pathway that quantifies the degree of alteration across the different experimental conditions. The results of the pathway analysis Inhibitors,research,lifescience,medical in the latter study, for example, implicate the Caspase inhibitor review involvement of several metabolic pathways in the aging process, such as C21 -steroid hormone metabolism, phospholipid degradation, prostaglandin and leukotriene metabolism, 2,4-dichloro benzoate degradation, and fatty acid biosynthesis. Interestingly, pathways operative Inhibitors,research,lifescience,medical in neurodegenerative disease such as Inhibitors,research,lifescience,medical Huntington’s disease (HD),50,51
dentatorubral-pallidoluysian atrophy (DRPLA),52 and amyotrophic lateral sclerosis (ALS)53 also showed significant age-dependent expression changes. Databases, standardization initiatives, and common platforms It has been recognized that, there is a fundamental need worldwide to share microarray data in order to correlate researchers’ results with already published data. Since for such a task it is necessary to provide the raw data, large microarray databases have been set up as public repositories (for
example the gene expression omnibus (GEO) from NCBI54 and ArrayExpress from EBT55). Functional annotation is provided by the GO consortium.56 Inhibitors,research,lifescience,medical The aim of GO is to maintain a consistent, speciesindependent, functional description of gene products. GO terms have a. defined parent-child relationship and form a directed acyclic graph (DAG). At, the root, of the GO are the three top-level categories – molecular function, biological process, and Inhibitors,research,lifescience,medical cellular component – which contain many levels of child nodes (GO terms) that describe a gene product with increasing specificity. There are several tools for mining these annotations. We have developed the GOblet server that computes GO-term graph annotation for DNA sequences comprising several different sequence databases.57,58 A particular data repository for neuroscience applications is the National Brain Databank, MycoClean Mycoplasma Removal Kit a publicly accessible gene expression repository for the collection and dissemination of results from postmortem studies of neurological and psychiatric disorders. The project has been developed by the Harvard Brain Tissue Resource Center (HBTRC) in collaboration with Akaza Research, as an online resource for the neuroscience community. A further useful database for drug discovery and drug response screening is PharmGKB.