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      FunnyBase: a systems level functional annotation of Fundulus ESTs for the analysis of gene expression

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          Abstract

          BackgroundWhile studies of non-model organisms are critical for many research areas, such as evolution, development, and environmental biology, they present particular challenges for both experimental and computational genomic level research. Resources such as mass-produced microarrays and the computational tools linking these data to functional annotation at the system and pathway level are rarely available for non-model species. This type of "systems-level" analysis is critical to the understanding of patterns of gene expression that underlie biological processes.ResultsWe describe a bioinformatics pipeline known as FunnyBase that has been used to store, annotate, and analyze 40,363 expressed sequence tags (ESTs) from the heart and liver of the fish, Fundulus heteroclitus. Primary annotations based on sequence similarity are linked to networks of systematic annotation in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and can be queried and computationally utilized in downstream analyses. Steps are taken to ensure that the annotation is self-consistent and that the structure of GO is used to identify higher level functions that may not be annotated directly. An integrated framework for cDNA library production, sequencing, quality control, expression data generation, and systems-level analysis is presented and utilized. In a case study, a set of genes, that had statistically significant regression between gene expression levels and environmental temperature along the Atlantic Coast, shows a statistically significant (P < 0.001) enrichment in genes associated with amine metabolism.ConclusionThe methods described have application for functional genomics studies, particularly among non-model organisms. The web interface for FunnyBase can be accessed at . Data and source code are available by request at jpaschall@bioinfobase.umkc.edu.

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          Most cited references 58

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          Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.

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            Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.

            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 epithelial/estrogen receptor-positive 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.
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              Basic Local Alignment Search Tool

               S Altschul (1990)
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                Author and article information

                Affiliations
                [1 ]Division of Molecular Biology and Biochemistry, 5100 Rockhill Rd., University of Missouri-Kansas City 64110, USA
                [2 ]Department of Environmental & Molecular Toxicology, North Carolina State University; Raleigh, NC 27695-7633 USA
                [3 ]Division of Marine Biology and Fisheries, NIEHS Marine and Freshwater Biomedical Sciences Center, Rosenstiel School of Marine & Atmospheric Science, University of Miami, Miami, FL 33149, USA
                Contributors
                Journal
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                2004
                20 December 2004
                : 5
                : 96
                544896
                1471-2164-5-96
                15610557
                10.1186/1471-2164-5-96
                Copyright © 2004 Paschall et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Research Article

                Genetics

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