Unknown

Dataset Information

0

Revealing global regulatory perturbations across human cancers.


ABSTRACT: The discovery of pathways and regulatory networks whose perturbation contributes to neoplastic transformation remains a fundamental challenge for cancer biology. We show that such pathway perturbations, and the cis-regulatory elements through which they operate, can be efficiently extracted from global gene expression profiles. Our approach utilizes information-theoretic analysis of expression levels, pathways, and genomic sequences. Analysis across a diverse set of human cancers reveals the majority of previously known cancer pathways. Through de novo motif discovery we associate these pathways with transcription-factor binding sites and miRNA targets, including those of E2F, NF-Y, p53, and let-7. Follow-up experiments confirmed that these predictions correspond to functional in vivo regulatory interactions. Strikingly, the majority of the perturbations, associated with putative cis-regulatory elements, fall outside of known cancer pathways. Our study provides a systems-level dissection of regulatory perturbations in cancer-an essential component of a rational strategy for therapeutic intervention and drug-target discovery.

SUBMITTER: Goodarzi H 

PROVIDER: S-EPMC2900319 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC6400502 | biostudies-literature
| S-EPMC3039912 | biostudies-literature
| S-EPMC6323961 | biostudies-literature
| S-EPMC6599967 | biostudies-literature
| S-EPMC1309705 | biostudies-literature
| S-EPMC2848990 | biostudies-literature
| S-EPMC4008137 | biostudies-literature
| S-EPMC3667745 | biostudies-literature
| S-EPMC6953167 | biostudies-literature
| S-EPMC3697090 | biostudies-literature