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2013 ; 7
(Suppl 7
): S2
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Conceptualization of molecular findings by mining gene annotations
#MMPMID24564884
Chen V
; Lu X
BMC Proc
2013[Dec]; 7
(Suppl 7
): S2
PMID24564884
show ga
BACKGROUND: The Gene Ontology (GO) is an ontology representing molecular biology
concepts related to genes and their products. Current annotations from the GO
Consortium tend to be highly specific, and contemporary genome-scale studies
often return a long list of genes of potential interest, such as genes in a
cancer tumor that are differentially expressed than those found in normal tissue.
It is therefore a challenging task to reveal, at a conceptual level, the major
functional themes in which genes are involved. Presently, there is a need for
tools capable of revealing such themes through mining and representing semantic
information in an objective and quantitative manner. METHODS: In this study, we
utilized the hierarchical organization of the GO to derive a more abstract
representation of the major biological processes of a list of genes based on
their annotations. We cast the task as follows: given a list of genes, identify
non-disjoint, functionally coherent subsets, such that the functions of the genes
in a subset are summarized by an informative GO term that accurately captures the
semantic information of the original annotations. RESULTS: We evaluated different
metrics for assessing information loss when merging GO terms, and different
statistical schemes to assess the functional coherence of a set of genes. We
found that the best discriminative power was achieved by using a combination of
the information-content-based measure as the information-loss metric, and the
graph-based statistics derived from a Steiner tree connecting genes in an
augmented GO graph. CONCLUSIONS: Our methods provide an objective and
quantitative approach to capturing the major directions of gene functions in a
context-specific fashion.