Related Experiment Video

Updated: Aug 1, 2025

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
07:40

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions

Published on: May 27, 2021

4.2K

Synthetic lethality prediction in DNA damage repair, chromatin remodeling and the cell cycle using multi-omics data

Magda Markowska1,2, Magdalena A Budzinska1,3, Anna Coenen-Stass4

  • 1Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, Stefana Banacha 2, 02-097, Warsaw, Poland.

Scientific Reports
|April 29, 2023
PubMed

Insights

We developed SLIDE-VIP, a new computational framework to identify synthetic lethal (SL) gene interactions for cancer therapy. This method significantly reduces candidate pairs, uncovering potential drug targets from complex biological data.

Area of Science:

  • Computational Biology
  • Genomics
  • Cancer Research

Background:

  • Identifying synthetic lethal (SL) gene interactions is crucial for developing targeted cancer therapies.
  • Challenges include the vast number of gene pairs and data noise, hindering robust discovery.

Purpose of the Study:

  • To introduce SLIDE-VIP, a novel framework for discovering robust SL gene interactions.
  • To leverage multi-omics data for enhanced identification of clinically relevant SL pairs.

Main Methods:

  • SLIDE-VIP integrates eight statistical tests, including a new patient data-based test (iSurvLRT).
  • Utilizes multi-omics data from cell line screens, patient data, drug screens, and gene pathways.
  • Applied to identify SL interactions among DNA repair, chromatin remodeling, and cell cycle genes.

Main Results:

  • Reduced the search space from 200,000 to 883 high-confidence SL candidates.
  • Validated known SL pairs (e.g., RB1-E2F3, PRKDC-ATM) and proposed novel candidates (e.g., PTEN-PIK3CB).
  • Drug screen and pathway analyses provided corroboration and biological insights.

Conclusions:

  • SLIDE-VIP effectively identifies SL interactions with significant clinical potential.
  • The framework facilitates the discovery of novel therapeutic targets in cancer.
  • Analysis and visualizations are accessible via the SLIDE-VIP WebApp.

More Related Videos

Author Spotlight: Decoding DNA Repair by Extrachromosomal NHEJ Assay and HR Assays09:29

Author Spotlight: Decoding DNA Repair by Extrachromosomal NHEJ Assay and HR Assays

Published on: February 2, 2024

2.4K
MEDUSA for Identifying Death Regulatory Genes in Chemo-genetic Profiling Data07:17

MEDUSA for Identifying Death Regulatory Genes in Chemo-genetic Profiling Data

Published on: February 7, 2025

548

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
12.7K
DNA Damage Can Stall the Cell Cycle02:37

DNA Damage Can Stall the Cell Cycle

2.6K
Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
31.2K
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.6K
Genomics02:02

Genomics

Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
36.6K