Cargando…
SL-BioDP: Multi-Cancer Interactive Tool for Prediction of Synthetic Lethality and Response to Cancer Treatment
Synthetic lethality exploits the phenomenon that a mutation in a cancer gene is often associated with new vulnerability which can be uniquely targeted therapeutically, leading to a significant increase in favorable outcome. DNA damage and survival pathways are among the most commonly mutated network...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895978/ https://www.ncbi.nlm.nih.gov/pubmed/31671773 http://dx.doi.org/10.3390/cancers11111682 |
_version_ | 1783476677034115072 |
---|---|
author | Deng, Xiang Das, Shaoli Valdez, Kristin Camphausen, Kevin Shankavaram, Uma |
author_facet | Deng, Xiang Das, Shaoli Valdez, Kristin Camphausen, Kevin Shankavaram, Uma |
author_sort | Deng, Xiang |
collection | PubMed |
description | Synthetic lethality exploits the phenomenon that a mutation in a cancer gene is often associated with new vulnerability which can be uniquely targeted therapeutically, leading to a significant increase in favorable outcome. DNA damage and survival pathways are among the most commonly mutated networks in human cancers. Recent data suggest that synthetic lethal interactions between a tumor defect and a DNA repair pathway can be used to preferentially kill tumor cells. We recently published a method, DiscoverSL, using multi-omic cancer data, that can predict synthetic lethal interactions of potential clinical relevance. Here, we apply the generality of our models in a comprehensive web tool called Synthetic Lethality Bio Discovery Portal (SL-BioDP) and extend the cancer types to 18 cancer genome atlas cohorts. SL-BioDP enables a data-driven computational approach to predict synthetic lethal interactions from hallmark cancer pathways by mining cancer’s genomic and chemical interactions. Our tool provides queries and visualizations for exploring potentially targetable synthetic lethal interactions, shows Kaplan–Meier plots of clinical relevance, and provides in silico validation using short hairpin RNA (shRNA) and drug efficacy data. Our method would thus shed light on mechanisms of synthetic lethal interactions and lead to the discovery of novel anticancer drugs. |
format | Online Article Text |
id | pubmed-6895978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68959782019-12-24 SL-BioDP: Multi-Cancer Interactive Tool for Prediction of Synthetic Lethality and Response to Cancer Treatment Deng, Xiang Das, Shaoli Valdez, Kristin Camphausen, Kevin Shankavaram, Uma Cancers (Basel) Article Synthetic lethality exploits the phenomenon that a mutation in a cancer gene is often associated with new vulnerability which can be uniquely targeted therapeutically, leading to a significant increase in favorable outcome. DNA damage and survival pathways are among the most commonly mutated networks in human cancers. Recent data suggest that synthetic lethal interactions between a tumor defect and a DNA repair pathway can be used to preferentially kill tumor cells. We recently published a method, DiscoverSL, using multi-omic cancer data, that can predict synthetic lethal interactions of potential clinical relevance. Here, we apply the generality of our models in a comprehensive web tool called Synthetic Lethality Bio Discovery Portal (SL-BioDP) and extend the cancer types to 18 cancer genome atlas cohorts. SL-BioDP enables a data-driven computational approach to predict synthetic lethal interactions from hallmark cancer pathways by mining cancer’s genomic and chemical interactions. Our tool provides queries and visualizations for exploring potentially targetable synthetic lethal interactions, shows Kaplan–Meier plots of clinical relevance, and provides in silico validation using short hairpin RNA (shRNA) and drug efficacy data. Our method would thus shed light on mechanisms of synthetic lethal interactions and lead to the discovery of novel anticancer drugs. MDPI 2019-10-29 /pmc/articles/PMC6895978/ /pubmed/31671773 http://dx.doi.org/10.3390/cancers11111682 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Deng, Xiang Das, Shaoli Valdez, Kristin Camphausen, Kevin Shankavaram, Uma SL-BioDP: Multi-Cancer Interactive Tool for Prediction of Synthetic Lethality and Response to Cancer Treatment |
title | SL-BioDP: Multi-Cancer Interactive Tool for Prediction of Synthetic Lethality and Response to Cancer Treatment |
title_full | SL-BioDP: Multi-Cancer Interactive Tool for Prediction of Synthetic Lethality and Response to Cancer Treatment |
title_fullStr | SL-BioDP: Multi-Cancer Interactive Tool for Prediction of Synthetic Lethality and Response to Cancer Treatment |
title_full_unstemmed | SL-BioDP: Multi-Cancer Interactive Tool for Prediction of Synthetic Lethality and Response to Cancer Treatment |
title_short | SL-BioDP: Multi-Cancer Interactive Tool for Prediction of Synthetic Lethality and Response to Cancer Treatment |
title_sort | sl-biodp: multi-cancer interactive tool for prediction of synthetic lethality and response to cancer treatment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895978/ https://www.ncbi.nlm.nih.gov/pubmed/31671773 http://dx.doi.org/10.3390/cancers11111682 |
work_keys_str_mv | AT dengxiang slbiodpmulticancerinteractivetoolforpredictionofsyntheticlethalityandresponsetocancertreatment AT dasshaoli slbiodpmulticancerinteractivetoolforpredictionofsyntheticlethalityandresponsetocancertreatment AT valdezkristin slbiodpmulticancerinteractivetoolforpredictionofsyntheticlethalityandresponsetocancertreatment AT camphausenkevin slbiodpmulticancerinteractivetoolforpredictionofsyntheticlethalityandresponsetocancertreatment AT shankavaramuma slbiodpmulticancerinteractivetoolforpredictionofsyntheticlethalityandresponsetocancertreatment |