InDePTH: detection of hub genes for developing gene expression networks under anticancer drug treatment

Masaru Koido1, Yuri Tani1, Satomi Tsukahara1

  • 1Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.

Oncotarget
|July 19, 2018
PubMed

Insights

This study introduces a new algorithm to identify key genes in cancer drug response networks. The method accurately pinpoints crucial regulatory genes, aiding in understanding drug effects on gene networks.

Area of Science:

  • Bioinformatics
  • Systems Biology
  • Genomics

Background:

  • Understanding gene regulatory networks (GRNs) under anticancer drug treatment is challenging.
  • Identifying key regulatory genes is crucial for deciphering drug mechanisms.

Purpose of the Study:

  • To develop a novel algorithm for identifying hub genes in drug-induced gene regulatory networks.
  • To provide a data-driven approach for understanding gene regulation during cancer therapy.

Main Methods:

  • Developed an algorithm to identify hub genes from differentially expressed genes.
  • Defined gene relationship directionality using transcriptome profiles from gene knockdown and overexpression experiments.
  • Validated the algorithm's ability to identify biologically relevant transcription factors.

Main Results:

  • The algorithm successfully identified plausible hub genes, including transcription factors, within drug-perturbed gene sets.
  • Validation experiments confirmed the role of identified hub genes in gene regulatory networks associated with cell growth inhibition.
  • The approach outperformed traditional methods like fold-change ranking and gene set enrichment analysis.

Conclusions:

  • The developed algorithm effectively highlights critical hub genes in anticancer drug-induced gene regulatory networks.
  • This data-driven method facilitates a deeper understanding of drug-induced gene regulation.
  • It offers a valuable tool for identifying potential functional genes in cancer drug discovery.

Related Concept Videos

What is Gene Expression?01:42

What is Gene Expression?

Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
196.9K
What is Gene Expression?01:36

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
11.5K
Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
24.9K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.6K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

5.6K