Exploring biomedical and chemical data sources
with TargetMine, a data warehouse system fortarget discovery
http://www.mizuguchilab.org/
1,2
1
1,2,Yi-An Chen , Lokesh P. Tripathi , Kenji Mizuguchi *1 National Institute of Biomedical Innovation, 7-6-8 Saito Asagi, Ibaraki, Osaka, 567-0085, Japan.
2 Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka, 565-0871, Japan.

*E-mail : kenji@nibio.go.jp

Abstract

Gene prioritisation with TargetMine

We have recently developed TargetMine†, an integrated datawarehouse for target discovery, which is based on the flexible
InterMine framework and effectively combines biological data fromseveral public resources. It enables biological data gathering and data
analysis in a single user-friendly interface and it is, thus, a useful tool
to assist in candidate gene selection. TargetMine has been effectively
employed for target selection in a protein interaction network-based
investigation of Hepatitis C virus (HCV) pathogenesis. For the purposeof drug discovery, we have now included in TargetMine some moredata about chemical compounds and their associations with proteins.
We have also incorporated new data sources for biological pathways
and interactions. The enhanced data warehouse facilitates more
complicated queries and new ideas for prioritizing targets.

We propose a protocol for target gene prioritisation using TargetMine.

The academic version of TargetMine is available at

The prioritisation protocol was benchmarked on 19 sets of genes
known to be associated with various human diseases.

http://targetmine.nibio.go.jp/ .

(1) Upload candidate genes
to TargetMine(2) Identify the enrichedbiological themes

List

Background302010(3) Select genes in theenriched biological themes

0hsa05330 hsa00982 hsa00980

Enrichment analysis

Data sources
Integrated data sources in TargetMine
newnew

InterProDisease Ontology

Gathering genes mapped
to the top seven enrichedbiological themes ensured
optimal target discovery
ENZYMEnomenclature databasenewnew
new

iRefIndex

Using TargetMine

56 human proteins found tointeract with HCV proteins Coreand NS4B in membrane yeast
two-hybrid screens

TargetMine features a sequence ontology based data model with auser-friendly web interface that allows the end users to constructflexible and complex queries. The users may also choose from alibrary of ‘templates’ consisting of diverse predefined queries with asimple form and description.

siRNA knockdown of selected targets ENO1
and SLC25A5 affected HCV propagation
log10% of Control HCV RNA Production

newApplication:
TargetMine has been effectively employed for target selection in theinvestigation of hepatitis C virus (HCV) pathogenesis#.

3*2*

10ControlENO1

PXN

SLC25A5459 genes in HCV infection
networks; four targets selectedfor experimental investigation% of Control HCV RNA Production

siRNA knockdown of selected targets ENO1and PXN significantly decreased HCV replication

1007550*

250ControlENO1*PXN

SLC25A5Conclusions
TargetMine is an integrated data warehouse that enables complicatedsearches that are difficult to perform using existing comparable tools
and therefore, assists in efficient target prioritisation.
†Chen YA, Tripathi LP, Mizuguchi K: TargetMine, an integrated data warehouse for candidate gene prioritisation and target discovery. PloS One 6: e17844, 2011.
# Tripathi LP, Kataoka C, Taguwa S, Moriishi K, Mori Y, Matsuura Y, Mizuguchi K: Network based analysis of Hepatitis C virus Core and NS4B protein interactions. Mol Biosyst 6, 2539-53, 2010