0000000000286452
AUTHOR
François Képès
CiliaCarta: An integrated and validated compendium of ciliary genes
The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We generated independent experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins using multiple cell and animal model systems (mouse…
SYSCILIA, “A systems biology approach to dissect cilia function and its disruption in human genetic disease”
Primary cilia are basically signaling hubs, harboring amongst others the noncanonical WNT, Hedgehog,and PDGF signaling systems, and their disruption leads to striking developmental defects. Some ciliopathy-associated proteins have recently been revealed to be physically or functionally associated in several distinct groupings, with limited connections to other crucial biological processes. Early proteomics studies have also suggested a discrete repertoire of about 1000 proteins within the organelle (i.e. <5% of the proteome) that are still in need of organisation into pathways and networks. Small, relatively isolated systems are often targeted by systems biology approaches under the assumpt…