TY - JOUR
T1 - GUILDify v2.0
T2 - A Tool to Identify Molecular Networks Underlying Human Diseases, Their Comorbidities and Their Druggable Targets
AU - Aguirre-Plans, Joaquim
AU - Piñero, Janet
AU - Sanz, Ferran
AU - Furlong, Laura I.
AU - Fernandez-Fuentes, Narcis
AU - Oliva, Baldo
AU - Guney, Emre
N1 - Funding Information:
The authors received support from the following: ISCIII–FEDER ( PI13/00082 , CP10/00524 , CPII16/00026 ); IMI-JU under grants agreements no. 116030 (TransQST) and no. 777365 (eTRANSAFE), resources of which are composed of financial contribution from the EU-FP7 ( FP7/2007- 2013 ) and EFPIA companies in kind contribution; the EU H2020 Programme 2014–2020 under grant agreements no. 634143 (MedBioinformatics) and no. 676559 (Elixir-Excelerate); the Spanish Ministry of Economy (MINECO) ( BIO2017-85329-R , RYC-2015-17519 ); and “Unidad de Excelencia María de Maeztu,” funded by the Spanish Ministry of Economy (ref.: MDM-2014-0370 ). The Research Programme on Biomedical Informatics is a member of the Spanish National Bioinformatics Institute, PRB2-ISCIII, and is supported by Grant PT13/0001/0023 of the PE I + D + i 2013-2016 funded by ISCIII and FEDER .
Funding Information:
J.A.P. and E.G. would like to acknowledge the technical support from Research Programme on Biomedical Informatics IT team, in particular A. Gonzalez Pauner and M.A. S?nchez G?mez. The authors received support from the following: ISCIII?FEDER (PI13/00082, CP10/00524, CPII16/00026); IMI-JU under grants agreements no. 116030 (TransQST) and no. 777365 (eTRANSAFE), resources of which are composed of financial contribution from the EU-FP7 (FP7/2007- 2013) and EFPIA companies in kind contribution; the EU H2020 Programme 2014?2020 under grant agreements no. 634143 (MedBioinformatics) and no. 676559 (Elixir-Excelerate); the Spanish Ministry of Economy (MINECO) (BIO2017-85329-R, RYC-2015-17519); and ?Unidad de Excelencia Mar?a de Maeztu,? funded by the Spanish Ministry of Economy (ref.: MDM-2014-0370). The Research Programme on Biomedical Informatics is a member of the Spanish National Bioinformatics Institute, PRB2-ISCIII, and is supported by Grant PT13/0001/0023 of the PE I + D + i 2013-2016 funded by ISCIII and FEDER. Conflicts of Interest Statement: None declared.
Funding Information:
The authors received support from the following: ISCIII–FEDER (PI13/00082, CP10/00524, CPII16/00026); IMI-JU under grants agreements no. 116030 (TransQST) and no. 777365 (eTRANSAFE), resources of which are composed of financial contribution from the EU-FP7 (FP7/2007- 2013) and EFPIA companies in kind contribution; the EU H2020 Programme 2014–2020 under grant agreements no. 634143 (MedBioinformatics) and no. 676559 (Elixir-Excelerate); the Spanish Ministry of Economy (MINECO) (BIO2017-85329-R, RYC-2015-17519); and “Unidad de Excelencia María de Maeztu,” funded by the Spanish Ministry of Economy (ref.: MDM-2014-0370). The Research Programme on Biomedical Informatics is a member of the Spanish National Bioinformatics Institute, PRB2-ISCIII, and is supported by Grant PT13/0001/0023 of the PE I + D + i 2013-2016 funded by ISCIII and FEDER.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/6/14
Y1 - 2019/6/14
N2 - The genetic basis of complex diseases involves alterations on multiple genes. Unraveling the interplay between these genetic factors is key to the discovery of new biomarkers and treatments. In 2014, we introduced GUILDify, a web server that searches for genes associated to diseases, finds novel disease genes applying various network-based prioritization algorithms and proposes candidate drugs. Here, we present GUILDify v2.0, a major update and improvement of the original method, where we have included protein interaction data for seven species and 22 human tissues and incorporated the disease–gene associations from DisGeNET. To infer potential disease relationships associated with multi-morbidities, we introduced a novel feature for estimating the genetic and functional overlap of two diseases using the top-ranking genes and the associated enrichment of biological functions and pathways (as defined by GO and Reactome). The analysis of this overlap helps to identify the mechanistic role of genes and protein–protein interactions in comorbidities. Finally, we provided an R package, guildifyR, to facilitate programmatic access to GUILDify v2.0 (http://sbi.upf.edu/guildify2)
AB - The genetic basis of complex diseases involves alterations on multiple genes. Unraveling the interplay between these genetic factors is key to the discovery of new biomarkers and treatments. In 2014, we introduced GUILDify, a web server that searches for genes associated to diseases, finds novel disease genes applying various network-based prioritization algorithms and proposes candidate drugs. Here, we present GUILDify v2.0, a major update and improvement of the original method, where we have included protein interaction data for seven species and 22 human tissues and incorporated the disease–gene associations from DisGeNET. To infer potential disease relationships associated with multi-morbidities, we introduced a novel feature for estimating the genetic and functional overlap of two diseases using the top-ranking genes and the associated enrichment of biological functions and pathways (as defined by GO and Reactome). The analysis of this overlap helps to identify the mechanistic role of genes and protein–protein interactions in comorbidities. Finally, we provided an R package, guildifyR, to facilitate programmatic access to GUILDify v2.0 (http://sbi.upf.edu/guildify2)
KW - traget prioritization
KW - systems medicine
KW - network analysis
KW - disease comorbidity
KW - drub repurposing
KW - drug repurposing
KW - target prioritization
KW - Genetic Predisposition to Disease
KW - Comorbidity
KW - Humans
KW - Computational Biology/methods
KW - Drug Design
KW - Gene Regulatory Networks/drug effects
KW - Software
UR - http://www.scopus.com/inward/record.url?scp=85062913663&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2019.02.027
DO - 10.1016/j.jmb.2019.02.027
M3 - Article
C2 - 30851278
SN - 0022-2836
VL - 431
SP - 2477
EP - 2484
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 13
ER -
