Functional modules integrating essential cellular functions are predictive of the response of leukaemia cells to DNA damage.

Abstract

Childhood B-precursor lymphoblastic leukaemia (ALL) is the most common paediatric malignancy. Despite the fact that 80% of ALL patients respond to anti-cancer drugs, the patho-physiology of this disease is still not fully understood. mRNA expression-profiling studies that have been performed have not yet provided novel insights into the mechanisms behind cellular response to DNA damage. More powerful data analysis techniques may be required for identifying novel functional pathways involved in the cellular responses to DNA damage. In order to explore the possibility that unforeseen biological processes may be involved in the response to DNA damage, we have developed and applied a novel procedure for the identification of functional modules in ALL cells. We have discovered that the overall activity of functional modules integrating protein degradation and mRNA processing is predictive of response to DNA damage. Supplementary material including R code, additional results, experimental datasets, as well as a detailed description of the methodology are available at http://www.bip.bham.ac.uk/vivo/fumo.html. Supplementary data are available at Bioinformatics online.