Imperial College London


Faculty of MedicineDepartment of Brain Sciences

Professor of Neurology and Genomic Medicine



m.johnson Website




E419Burlington DanesHammersmith Campus






BibTex format

author = {Delahaye-Duriez, A and Srivastava, P and Shkura, K and Langley, SR and Laaniste, L and Moreno-Moral, A and Danis, B and Foerch, P and Gazina, EV and Richards, K and Petrou, S and Kaminski, R and Petretto, E and Johnson, MR},
doi = {10.1186/s13059-016-1097-7},
journal = {Genome Biology},
title = {Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery},
url = {},
volume = {17},
year = {2016}

RIS format (EndNote, RefMan)

AB - BackgroundThe relationship between monogenic and polygenic forms of epilepsy is poorly understood, and the extent to which the genetic and acquired epilepsies share common pathways is unclear. Here, we use an integrated systems-level analysis of brain gene expression data to identify molecular networks disrupted in epilepsy.ResultsWe identify a co-expression network of 320 genes (M30), which is significantly enriched for non-synonymous de novo mutations ascertained from patients with monogenic epilepsy, and for common variants associated with polygenic epilepsy. The genes in M30 network are expressed widely in the human brain under tight developmental control, and encode physically interacting proteins involved in synaptic processes. The most highly connected proteins within M30 network are preferentially disrupted by deleterious de novo mutations for monogenic epilepsy, in line with the centrality-lethality hypothesis. Analysis of M30 expression revealed consistent down-regulation in the epileptic brain in heterogeneous forms of epilepsy including human temporal lobe epilepsy, a mouse model of acquired temporal lobe epilepsy, and a mouse model of monogenic Dravet (SCN1A) disease. These results suggest functional disruption of M30 via gene mutation or altered expression as a convergent mechanismregulating susceptibility to epilepsy broadly. Using the large collection of drug-induced gene expression data from Connectivity Map, several drugs were predicted to preferentially restore the down-regulation of M30 in epilepsy toward health, most notably valproic acid, whose effect on M30 expression was replicated in neurons.ConclusionsTaken together, our results suggest targeting the expression of M30 as a potential new therapeutic strategy in epilepsy.
AU - Delahaye-Duriez,A
AU - Srivastava,P
AU - Shkura,K
AU - Langley,SR
AU - Laaniste,L
AU - Moreno-Moral,A
AU - Danis,B
AU - Foerch,P
AU - Gazina,EV
AU - Richards,K
AU - Petrou,S
AU - Kaminski,R
AU - Petretto,E
AU - Johnson,MR
DO - 10.1186/s13059-016-1097-7
PY - 2016///
SN - 1474-760X
TI - Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery
T2 - Genome Biology
UR -
UR -
VL - 17
ER -