Protein interaction network topology uncovers melanogenesis regulatory network components within functional genomics datasets.
BACKGROUND
RNA-mediated interference (RNAi)-based functional genomics is a systems-level approach to identify novel genes that control biological phenotypes. Existing computational approaches can identify individual genes from RNAi datasets that regulate a given biological process. However, currently available methods cannot identify which RNAi screen "hits" are novel components of well-characterized biological pathways known to regulate the interrogated phenotype. In this study, we describe a method to identify genes from RNAi datasets that are novel components of known biological pathways. We experimentally validate our approach in the context of a recently completed RNAi screen to identify novel regulators of melanogenesis.


RESULTS
In this study, we utilize a PPI network topology-based approach to identify targets within our RNAi dataset that may be components of known melanogenesis regulatory pathways. Our computational approach identifies a set of screen targets that cluster topologically in a human PPI network with the known pigment regulator Endothelin receptor type B (EDNRB). Validation studies reveal that these genes impact pigment production and EDNRB signaling in pigmented melanoma cells (MNT-1) and normal melanocytes.


CONCLUSIONS
We present an approach that identifies novel components of well-characterized biological pathways from functional genomics datasets that could not have been identified by existing statistical and computational approaches.
Ho
Hsiang
H
Department of Biological Chemistry, University of California, Irvine, 92697-1700, USA.
Milenković
Tijana
T
Memisević
Vesna
V
Aruri
Jayavani
J
Przulj
Natasa
N
Ganesan
Anand K
AK
D019295:Computational Biology / Q000379:methods*; D053263:Gene Regulatory Networks / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D006801:Humans; D008543:Melanins / Q000096:biosynthesis* / Q000235:genetics; D008544:Melanocytes / Q000378:metabolism; D008954:Models, Biological; D025941:Protein Interaction Mapping / Q000379:methods*; D034622:RNA Interference; D044023:Receptor, Endothelin B / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
D008543:Melanins; D044023:Receptor, Endothelin B