SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets

Synthetic lethality (SL) is a type of genetic interaction between two genes such that simultaneous perturbations of the two genes result in cell death or a dramatic decrease of cell viability, while a perturbation of either gene alone is not lethal. SL reflects the biologically endogenous difference...

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Main Authors:	Guo, Jing, Liu, Hui, Zheng, Jie
Format:	Online
Language:	English
Published:	Oxford University Press 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702809/

id	pubmed-4702809
recordtype	oai_dc
spelling	pubmed-47028092016-01-07 SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets Guo, Jing Liu, Hui Zheng, Jie Database Issue Synthetic lethality (SL) is a type of genetic interaction between two genes such that simultaneous perturbations of the two genes result in cell death or a dramatic decrease of cell viability, while a perturbation of either gene alone is not lethal. SL reflects the biologically endogenous difference between cancer cells and normal cells, and thus the inhibition of SL partners of genes with cancer-specific mutations could selectively kill cancer cells but spare normal cells. Therefore, SL is emerging as a promising anticancer strategy that could potentially overcome the drawbacks of traditional chemotherapies by reducing severe side effects. Researchers have developed experimental technologies and computational prediction methods to identify SL gene pairs on human and a few model species. However, there has not been a comprehensive database dedicated to collecting SL pairs and related knowledge. In this paper, we propose a comprehensive database, SynLethDB (http://histone.sce.ntu.edu.sg/SynLethDB/), which contains SL pairs collected from biochemical assays, other related databases, computational predictions and text mining results on human and four model species, i.e. mouse, fruit fly, worm and yeast. For each SL pair, a confidence score was calculated by integrating individual scores derived from different evidence sources. We also developed a statistical analysis module to estimate the druggability and sensitivity of cancer cells upon drug treatments targeting human SL partners, based on large-scale genomic data, gene expression profiles and drug sensitivity profiles on more than 1000 cancer cell lines. To help users access and mine the wealth of the data, we developed other practical functionalities, such as search and filtering, orthology search, gene set enrichment analysis. Furthermore, a user-friendly web interface has been implemented to facilitate data analysis and interpretation. With the integrated data sets and analytics functionalities, SynLethDB would be a useful resource for biomedical research community and pharmaceutical industry. Oxford University Press 2016-01-04 2015-10-29 /pmc/articles/PMC4702809/ /pubmed/26516187 http://dx.doi.org/10.1093/nar/gkv1108 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Guo, Jing Liu, Hui Zheng, Jie
spellingShingle	Guo, Jing Liu, Hui Zheng, Jie SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets
author_facet	Guo, Jing Liu, Hui Zheng, Jie
author_sort	Guo, Jing
title	SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets
title_short	SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets
title_full	SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets
title_fullStr	SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets
title_full_unstemmed	SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets
title_sort	synlethdb: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets
description	Synthetic lethality (SL) is a type of genetic interaction between two genes such that simultaneous perturbations of the two genes result in cell death or a dramatic decrease of cell viability, while a perturbation of either gene alone is not lethal. SL reflects the biologically endogenous difference between cancer cells and normal cells, and thus the inhibition of SL partners of genes with cancer-specific mutations could selectively kill cancer cells but spare normal cells. Therefore, SL is emerging as a promising anticancer strategy that could potentially overcome the drawbacks of traditional chemotherapies by reducing severe side effects. Researchers have developed experimental technologies and computational prediction methods to identify SL gene pairs on human and a few model species. However, there has not been a comprehensive database dedicated to collecting SL pairs and related knowledge. In this paper, we propose a comprehensive database, SynLethDB (http://histone.sce.ntu.edu.sg/SynLethDB/), which contains SL pairs collected from biochemical assays, other related databases, computational predictions and text mining results on human and four model species, i.e. mouse, fruit fly, worm and yeast. For each SL pair, a confidence score was calculated by integrating individual scores derived from different evidence sources. We also developed a statistical analysis module to estimate the druggability and sensitivity of cancer cells upon drug treatments targeting human SL partners, based on large-scale genomic data, gene expression profiles and drug sensitivity profiles on more than 1000 cancer cell lines. To help users access and mine the wealth of the data, we developed other practical functionalities, such as search and filtering, orthology search, gene set enrichment analysis. Furthermore, a user-friendly web interface has been implemented to facilitate data analysis and interpretation. With the integrated data sets and analytics functionalities, SynLethDB would be a useful resource for biomedical research community and pharmaceutical industry.
publisher	Oxford University Press
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702809/
_version_	1613520468895072256

SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets

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