Microarray meta-analysis database (M(2)DB): a uniformly pre-processed, quality controlled, and manually curated human clinical microarray database

Abstract

Background: Over the past decade, gene expression microarray studies have greatly expanded our knowledge of genetic mechanisms of human diseases. Meta-analysis of substantial amounts of accumulated data, by integrating valuable information from multiple studies, is becoming more important in microarray research. However, collecting data of special interest from public microarray repositories often present major practical problems. Moreover, including low-quality data may significantly reduce meta-analysis efficiency.

Results: M2DB is a human curated microarray database designed for easy querying, based on clinical information and for interactive retrieval of either raw or uniformly pre-processed data, along with a set of quality-control metrics. The database contains more than 10,000 previously published Affymetrix GeneChip arrays, performed using human clinical specimens. M2DB allows online querying according to a flexible combination of five clinical annotations describing disease state and sampling location. These annotations were manually curated by controlled vocabularies, based on information obtained from GEO, ArrayExpress, and published papers. For array-based assessment control, the online query provides sets of QC metrics, generated using three available QC algorithms. Arrays with poor data quality can easily be excluded from the query interface. The query provides values from two algorithms for gene-based filtering, and raw data and three kinds of pre-processed data for downloading.

Conclusion: M2DB utilizes a user-friendly interface for QC parameters, sample clinical annotations, and data formats to help users obtain clinical metadata. This database provides a lower entry threshold and an integrated process of meta-analysis. We hope that this research will promote further evolution of microarray meta-analysis.

Figure 1

Schematic process diagram of M²DB. Affymetrix GeneChip HG-U133A and HG-U133 Plus 2.0 arrays with CEL files are downloaded from GEO and ArrayExpress. Then, raw data was pre-processed using MAS5, RMA, and GCRMA. All arrays were annotated into five annotations via manual curation. Array quality assessed by SimpleAffy, PMVO, and MDQC packages in Bioconductor. MAS5call and labeling efficiency values (LEVs) are supplied for gene-based filtering for further analysis. Finally, all information was stored in M²DB.

Figure 2

Web query interface of M²DB. M²DB Web interface consists of three parts: 1). Sample selection according to sets of QC metrics and manually curated annotation, 2). The display of Experiment/Sample information, where the "additional selection box" enables to make further selection, and 3). Data Format and Submission panel.