Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.The accelerating availability of molecular sequences, particularly the sequences of entire genomes, has transformed both the theory and practice of experimental biology. Where once biochemists characterized proteins by their diverse activities and abundances, and geneticists characterized genes by the phenotypes of their mutations, all biologists now acknowledge that there is likely to be a single limited universe of genes and proteins, many of which are conserved in most or all living cells. This recognition has fuelled a grand unification of biology; the information about the shared genes and proteins contributes to our understanding of all the diverse organisms that share them. Knowledge of the biological role of such a shared protein in one organism can certainly illuminate, and often provide strong inference of, its role in other organisms.Progress in the way that biologists describe and conceptualize the shared biological elements has not kept pace with sequencing. For the most part, the current systems of nomenclature for genes and their products remain divergent even when the experts appreciate the underlying similarities. Interoperability of genomic databases is limited by this lack of progress, and it is this major obstacle that the Gene Ontology (GO) Consortium was formed to address.
The purpose of this study was to classify breast carcinomas based on variations in gene expression patterns derived from cDNA microarrays and to correlate tumor characteristics to clinical outcome. A total of 85 cDNA microarray experiments representing 78 cancers, three fibroadenomas, and four normal breast tissues were analyzed by hierarchical clustering. As reported previously, the cancers could be classified into a basal epithelial-like group, an ERBB2-overexpressing group and a normal breast-like group based on variations in gene expression. A novel finding was that the previously characterized luminal epithelial͞estrogen receptorpositive group could be divided into at least two subgroups, each with a distinctive expression profile. These subtypes proved to be reasonably robust by clustering using two different gene sets: first, a set of 456 cDNA clones previously selected to reflect intrinsic properties of the tumors and, second, a gene set that highly correlated with patient outcome. Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.
Microarray analysis has become a widely used tool for the generation of gene expression data on a genomic scale. Although many significant results have been derived from microarray studies, one limitation has been the lack of standards for presenting and exchanging such data. Here we present a proposal, the Minimum Information About a Microarray Experiment (MIAME), that describes the minimum information required to ensure that microarray data can be easily interpreted and that results derived from its analysis can be independently verified. The ultimate goal of this work is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools. With respect to MIAME, we concentrate on defining the content and structure of the necessary information rather than the technical format for capturing it.
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