AUTHOR=Ho Yen-Yi , Cope Leslie M., Parmigiani Giovanni 

TITLE=Modular network construction using eQTL data: an analysis of computational costs and benefits

JOURNAL=Frontiers in Genetics

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2014.00040

DOI=10.3389/fgene.2014.00040

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> In this paper, we consider analytic methods for the integrated analysis of genomic DNA variation and mRNA expression (also named as eQTL data), to discover genetic networks that are associated with a complex trait of interest. Our focus is the systematic evaluation of the trade-off between network size and network search efficiency in the construction of these networks.</p><p><bold>Results:</bold> We developed a modular approach to network construction, building from smaller networks to larger ones, thereby reducing the search space while including more variables in the analysis. The goal is achieving a lower computational cost while maintaining high confidence in the resulting networks. As demonstrated in our simulation results, networks built in this way have low node/edge false discovery rate (FDR) and high edge sensitivity comparing to greedy search. We further demonstrate our method in a data set of cellular responses to two chemotherapeutic agents: docetaxel and 5-fluorouracil (5-FU), and identify biologically plausible networks that might describe resistances to these drugs.</p><p><bold>Conclusion:</bold> In this study, we suggest that guided comprehensive searches for parsimonious networks should be considered as an alternative to greedy network searches.</p>