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Issue No.05 - Sept.-Oct. (2012 vol.9)
pp: 1399-1409
Nadeem A. Ansari , Microsoft Corp., Redmond, WA, USA
Riyue Bao , Dept. of Biol. Sci., Wayne State Univ., Detroit, MI, USA
Calin Voichita , Dept. of Comput. Sci., Wayne State Univ., Detroit, MI, USA
Sorin Draghici , Dept. of Obstetrics & Gynecology, Wayne State Univ., Detroit, MI, USA
ABSTRACT
High throughput technologies enable researchers to measure expression levels on a genomic scale. However, the correct and efficient biological interpretation of such voluminous data remains a challenging problem. Many tools have been developed for the analysis of GO terms that are over- or under-represented in a list of differentially expressed genes. However, a previously unexplored aspect is the identification of changes in the way various biological processes interact in a given condition with respect to a reference. Here, we present a novel approach that aims at identifying such interactions between biological processes that are significantly different in a given phenotype with respect to normal. The proposed technique uses vector-space representation, SVD-based dimensionality reduction, differential weighting, and bootstrapping to asses the significance of the interactions under the multiple and complex dependencies expected between the biological processes. We illustrate our approach on two real data sets involving breast and lung cancer. More than 88 percent of the interactions found by our approach were deemed to be correct by an extensive manual review of literature. An interesting subset of such interactions is discussed in detail and shown to have the potential to open new avenues for research in lung and breast cancer.
INDEX TERMS
singular value decomposition, biology computing, cancer, genomics, lab-on-a-chip, lung, medical computing, lung cancer, phenotype-specific interactions, biological processes, microarray data, microarray annotations, genomic scale, biological interpretation, voluminous data, differentially expressed genes, vector-space representation, SVD-based dimensionality reduction, differential weighting, bootstrapping, breast cancer, Biological processes, Correlation, Matrix decomposition, Vectors, Bioinformatics, Covariance matrix, single value decomposition., Phenotype-specific interactions, biological processes, microarrays, gene ontology
CITATION
Nadeem A. Ansari, Riyue Bao, Calin Voichita, Sorin Draghici, "Detecting Phenotype-Specific Interactions between Biological Processes from Microarray Data and Annotations", IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol.9, no. 5, pp. 1399-1409, Sept.-Oct. 2012, doi:10.1109/TCBB.2012.65
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