Apr 25, 2020

Efficient Representations of Tumor Diversity with Paired DNA-RNA Anomalies

BioRxiv : the Preprint Server for Biology
Q. KeDonald Geman


Cancer cells display massive dysregulation of key regulatory pathways due to now well- catalogued mutations and other DNA-related aberrations. Moreover, enormous heterogeneity has been commonly observed in the identity, frequency, and location of these aberrations across individuals with the same cancer type or subtype, and this variation naturally propagates to the transcriptome, resulting in myriad types of dysregulated gene expression programs. Many have argued that a more integrative and quantitative analysis of heterogeneity of DNA and RNA molecular profiles may be necessary for designing more systematic explorations of alternative therapies and improving predictive accuracy. We introduce a representation of multi-omics profiles which is sufficiently rich to account for observed heterogeneity and support the construction of quantitative, integrated metrics of variation. Starting from the network of interactions existing in Reactome, we build a library of "paired DNA- RNA anomalies" that represent prototypical and recurrent patterns of dysregulation in cancer; each two-gene "motif" consists of a "source" regulatory gene and a "target" gene whose expression is "controlled" by the source gene. The pair motif is then "active" ...Continue Reading

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Mentioned in this Paper

Meta Analysis (Statistical Procedure)
Nucleic Acid Sequencing
probe gene fragment

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