Abstract
Understanding and predicting phenotypic effects of gene copy number variations is for understanding for understanding the way in which cell buffers expression changes and in for diseases studies. Genetic alterations propagate trough the molecular system disrupting biological activities within cells. In particular, it has become clear that deviations from normal gene dosage are associated with multiple disorders in a range of species including humans. Genome-wide expression profiling Drosophila melanogaster deficiency heterozygotes reveals diverse genomic responses. We have systematically examined deficiencies on the left arm of chromosome 2 and (i) characterize gene-by-gene dosage responses/compensations (ii) their impact on gene network (iii) their impact expression noise and (iv) developed methods to utilize this data to study TF-gene regulation. We show that, surprisingly, expression noise was increased by gene dosage compensation – a property of gene deletions that could contribute to the phenotypic heterogeneity of diseases associated with haploinsufficiency. Additionally, we show that both – expression chances and expression variations associated with reduced dose of transcription factors propagate through the gene interaction network, impacting a large number of downstream genes. Finally, we utilized our data to learn new regulatory interaction vie a new iterative algorithm called Rewire Network Component Analysis (Rewire_NCA) that we developed for this purpose.