Cargando…

Synthetic Lethality-based Identification of Targets for Anticancer Drugs in the Human Signaling Network

Chemotherapy agents can cause serious adverse effects by attacking both cancer tissues and normal tissues. Therefore, we proposed a synthetic lethality (SL) concept-based computational method to identify specific anticancer drug targets. First, a 3-step screening strategy (network-based, frequency-b...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Lei, Chen, Xiujie, Hu, Chunyu, Zhang, Denan, Shao, Zhuo, Jin, Qing, Yang, Jingbo, Xie, Hongbo, Liu, Bo, Hu, Ming, Ke, Kehui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981615/
https://www.ncbi.nlm.nih.gov/pubmed/29855504
http://dx.doi.org/10.1038/s41598-018-26783-w
_version_ 1783328080320790528
author Liu, Lei
Chen, Xiujie
Hu, Chunyu
Zhang, Denan
Shao, Zhuo
Jin, Qing
Yang, Jingbo
Xie, Hongbo
Liu, Bo
Hu, Ming
Ke, Kehui
author_facet Liu, Lei
Chen, Xiujie
Hu, Chunyu
Zhang, Denan
Shao, Zhuo
Jin, Qing
Yang, Jingbo
Xie, Hongbo
Liu, Bo
Hu, Ming
Ke, Kehui
author_sort Liu, Lei
collection PubMed
description Chemotherapy agents can cause serious adverse effects by attacking both cancer tissues and normal tissues. Therefore, we proposed a synthetic lethality (SL) concept-based computational method to identify specific anticancer drug targets. First, a 3-step screening strategy (network-based, frequency-based and function-based screening) was proposed to identify the SL gene pairs by mining 697 cancer genes and the human signaling network, which had 6306 proteins and 62937 protein-protein interactions. The network-based screening was composed of a stability score constructed using a network information centrality measure (the average shortest path length) and the distance-based screening between the cancer gene and the non-cancer gene. Then, the non-cancer genes were extracted and annotated using drug-target interaction and drug description information to obtain potential anticancer drug targets. Finally, the human SL data in SynLethDB, the existing drug sensitivity data and text-mining were utilized for target validation. We successfully identified 2555 SL gene pairs and 57 potential anticancer drug targets. Among them, CDK1, CDK2, PLK1 and WEE1 were verified by all three aspects and could be preferentially used in specific targeted therapy in the future.
format Online
Article
Text
id pubmed-5981615
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-59816152018-06-07 Synthetic Lethality-based Identification of Targets for Anticancer Drugs in the Human Signaling Network Liu, Lei Chen, Xiujie Hu, Chunyu Zhang, Denan Shao, Zhuo Jin, Qing Yang, Jingbo Xie, Hongbo Liu, Bo Hu, Ming Ke, Kehui Sci Rep Article Chemotherapy agents can cause serious adverse effects by attacking both cancer tissues and normal tissues. Therefore, we proposed a synthetic lethality (SL) concept-based computational method to identify specific anticancer drug targets. First, a 3-step screening strategy (network-based, frequency-based and function-based screening) was proposed to identify the SL gene pairs by mining 697 cancer genes and the human signaling network, which had 6306 proteins and 62937 protein-protein interactions. The network-based screening was composed of a stability score constructed using a network information centrality measure (the average shortest path length) and the distance-based screening between the cancer gene and the non-cancer gene. Then, the non-cancer genes were extracted and annotated using drug-target interaction and drug description information to obtain potential anticancer drug targets. Finally, the human SL data in SynLethDB, the existing drug sensitivity data and text-mining were utilized for target validation. We successfully identified 2555 SL gene pairs and 57 potential anticancer drug targets. Among them, CDK1, CDK2, PLK1 and WEE1 were verified by all three aspects and could be preferentially used in specific targeted therapy in the future. Nature Publishing Group UK 2018-05-31 /pmc/articles/PMC5981615/ /pubmed/29855504 http://dx.doi.org/10.1038/s41598-018-26783-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Liu, Lei
Chen, Xiujie
Hu, Chunyu
Zhang, Denan
Shao, Zhuo
Jin, Qing
Yang, Jingbo
Xie, Hongbo
Liu, Bo
Hu, Ming
Ke, Kehui
Synthetic Lethality-based Identification of Targets for Anticancer Drugs in the Human Signaling Network
title Synthetic Lethality-based Identification of Targets for Anticancer Drugs in the Human Signaling Network
title_full Synthetic Lethality-based Identification of Targets for Anticancer Drugs in the Human Signaling Network
title_fullStr Synthetic Lethality-based Identification of Targets for Anticancer Drugs in the Human Signaling Network
title_full_unstemmed Synthetic Lethality-based Identification of Targets for Anticancer Drugs in the Human Signaling Network
title_short Synthetic Lethality-based Identification of Targets for Anticancer Drugs in the Human Signaling Network
title_sort synthetic lethality-based identification of targets for anticancer drugs in the human signaling network
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981615/
https://www.ncbi.nlm.nih.gov/pubmed/29855504
http://dx.doi.org/10.1038/s41598-018-26783-w
work_keys_str_mv AT liulei syntheticlethalitybasedidentificationoftargetsforanticancerdrugsinthehumansignalingnetwork
AT chenxiujie syntheticlethalitybasedidentificationoftargetsforanticancerdrugsinthehumansignalingnetwork
AT huchunyu syntheticlethalitybasedidentificationoftargetsforanticancerdrugsinthehumansignalingnetwork
AT zhangdenan syntheticlethalitybasedidentificationoftargetsforanticancerdrugsinthehumansignalingnetwork
AT shaozhuo syntheticlethalitybasedidentificationoftargetsforanticancerdrugsinthehumansignalingnetwork
AT jinqing syntheticlethalitybasedidentificationoftargetsforanticancerdrugsinthehumansignalingnetwork
AT yangjingbo syntheticlethalitybasedidentificationoftargetsforanticancerdrugsinthehumansignalingnetwork
AT xiehongbo syntheticlethalitybasedidentificationoftargetsforanticancerdrugsinthehumansignalingnetwork
AT liubo syntheticlethalitybasedidentificationoftargetsforanticancerdrugsinthehumansignalingnetwork
AT huming syntheticlethalitybasedidentificationoftargetsforanticancerdrugsinthehumansignalingnetwork
AT kekehui syntheticlethalitybasedidentificationoftargetsforanticancerdrugsinthehumansignalingnetwork