title: Revealing complex function, process and pathway interactions with high-throughput expression and biological annotation data.
abstract: The biological relationships both between and within the functions, processes and pathways that operate within complex biological systems are only poorly characterized, making the interpretation of large scale gene expression datasets extremely challenging. Here, we present an approach that integrates gene expression and biological annotation data to identify and describe the interactions between biological functions, processes and pathways that govern a phenotype of interest. The product is a global, interconnected network, not of genes but of functions, processes and pathways, that represents the biological relationships within the system. We validated our approach on two high-throughput expression datasets describing organismal and organ development. Our findings are well supported by the available literature, confirming that developmental processes and apoptosis play key roles in cell differentiation. Furthermore, our results suggest that processes related to pluripotency and lineage commitment, which are known to be critical for development, interact mainly indirectly, through genes implicated in more general biological processes. Moreover, we provide evidence that supports the relevance of cell spatial organization in the developing liver for proper liver function. Our strategy can be viewed as an abstraction that is useful to interpret high-throughput data and devise further experiments.
authors: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Ernst-Heydemann-Str. 8, 18057 Rostock, Germany. fuellen@uni-rostock.de.
authors: Nitesh Kumar
authors: NK
authors: Singh
authors: Mathias
authors: M
authors: Ernst
authors: Volkmar
authors: V
authors: Liebscher
authors: Georg
authors: G
authors: Fuellen
authors: Leila
authors: L
authors: Taher
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D047108:Embryonic Development / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D006801:Humans; D051379:Mice; D058977:Molecular Sequence Annotation; D038081:Organogenesis / Q000235:genetics; D012038:Regeneration / Q000235:genetics; D015398:Signal Transduction