title: Syn-lethality: an integrative knowledge base of synthetic lethality towards discovery of selective anticancer therapies.
abstract: Synthetic lethality (SL) is a novel strategy for anticancer therapies, whereby mutations of two genes will kill a cell but mutation of a single gene will not. Therefore, a cancer-specific mutation combined with a drug-induced mutation, if they have SL interactions, will selectively kill cancer cells. While numerous SL interactions have been identified in yeast, only a few have been known in human. There is a pressing need to systematically discover and understand SL interactions specific to human cancer. In this paper, we present Syn-Lethality, the first integrative knowledge base of SL that is dedicated to human cancer. It integrates experimentally discovered and verified human SL gene pairs into a network, associated with annotations of gene function, pathway, and molecular mechanisms. It also includes yeast SL genes from high-throughput screenings which are mapped to orthologous human genes. Such an integrative knowledge base, organized as a relational database with user interface for searching and network visualization, will greatly expedite the discovery of novel anticancer drug targets based on synthetic lethality interactions. The database can be downloaded as a stand-alone Java application.
authors.affiliation: Bioinformatics Research Centre (BIRC), School of Computer Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798.
authors.forename: Xue-juan
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Bioinformatics Research Centre (BIRC), School of Computer Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798.
authors.forename: Shital K
authors.initials: SK
authors.lastname: Mishra
authors.affiliation: Institute for Infocomm Research (I2R), 1 Fusionopolis Way, Singapore 138632.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Bioinformatics Research Centre (BIRC), School of Computer Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Bioinformatics Research Centre (BIRC), School of Computer Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 ; Genome Institute of Singapore (GIS), Biopolis, Singapore 138672.
authors.forename: Jie
authors.identifier: 0000-0001-6774-9786
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D030541:Databases, Genetic; D055808:Drug Discovery; D053263:Gene Regulatory Networks; D005804:Genes, Lethal; D006801:Humans; D051188:Knowledge Bases; D058977:Molecular Sequence Annotation; D015398:Signal Transduction / Q000235:genetics; D014584:User-Computer Interface
chemical_list: D000970:Antineoplastic Agents