Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 100, Issue 14, Pages 8348-8353Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0832373100
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Funding
- NCI NIH HHS [R01 CA077097, CA77097] Funding Source: Medline
- NHGRI NIH HHS [HG01315, U24 HG001315, U41 HG001315, P41 HG001315] Funding Source: Medline
- NIGMS NIH HHS [U01 GM061374, R24 GM061374, GM61374] Funding Source: Medline
- NLM NIH HHS [LM06244] Funding Source: Medline
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Genomic sequencing is no longer a novelty, but gene function annotation remains a key challenge in modern biology. A variety of functional genomics experimental techniques are available, from classic methods such as affinity precipitation to advanced high-throughput techniques such as gene expression microarrays. In the future, more disparate methods will be developed, further increasing the need for integrated computational analysis of data generated by these studies. We address this problem with MAGIC (Multisource Association of Genes by Integration of Clusters), a general framework that uses formal Bayesian reasoning to integrate heterogeneous types of high-throughput biological data (such as large-scale two-hybrid screens and multiple microarray analyses) for accurate gene function prediction. The system formally incorporates expert knowledge about relative accuracies of data sources to combine them within a normative framework. MAGIC provides a belief level with its output that allows the user to vary the stringency of predictions. We applied MAGIC to Saccharomyces cerevisiae genetic and physical interactions, microarray, and transcription factor binding sites data and assessed the biological relevance of gene groupings using Gene Ontology annotations produced by the Saccaromyces Genome Database. We found that by creating functional groupings based on heterogeneous data types, MAGIC improved accuracy of the groupings compared with microarray analysis alone. We describe several of the biological gene groupings identified.
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