Nav: Home

Mapping cellular diversity by looking for common topics of gene control

April 09, 2019

A Belgian team of computational biologists led by Stein Aerts (VIB-KU Leuven) has developed a new bioinformatics method called cisTopic. Inspired by text-mining methods, cisTopic helps scientists to gain insight into the mechanisms underlying the differences in gene regulation across and within the cells in our body by looking for common topics. In a new publication in Nature Methods, Aerts and his team demonstrate the broad range of applications of this method, from brain research to cancer biology.

Our genomes are controlled by combinations of regulatory molecules that "switch on" target genes in our DNA. These regulatory molecules bind to so-called enhancer and promoter regions in our chromosomes. Understanding when and how they are activated, can teach us a lot about the cellular diversity in our bodies.

"All the cells in our body essentially contain the same DNA," explains prof. Stein Aerts, who heads the lab for computational biology at VIB and KU Leuven. "What makes every cell type unique is which genes are active at any given time."

Recent advances in single-cell technology have enabled scientists like Aerts to look at gene activity and the accessibility of regulatory DNA regions for thousands of individual cells. But this information has not yet solved the challenge of reverse engineering the genomic regulatory code.

Clustering cells

Carmen Bravo González-Blas and Liesbeth Minnoye, two young researchers in Aerts' lab, set out to tackle this problem. "The data we can obtain from a single cell, regarding accessibility of specific regulatory regions in its DNA, is very sparse. Yet, we wanted to group individual cells into clusters based on similarities of these accessible regions."

To tackle this problem, Bravo González-Blas borrowed a computational technique from the text-mining field, called "topic modelling". She explains: "In text mining, computers can discover "topics" from large collections of text, as well as terms that are important for each topic. When applied to our problem of gene control, the computer discovers topics that are important for each cell type in our body. It also allowed us to identify regulatory regions for each topic."

"We evaluated our new method on a variety of data sets, and found that it allows us to accurately recover both expected and new cell types," adds Minnoye. "Particularly on very sparse data, our method is more robust than previously developed approaches."

Learning more about complex tissues

The researchers applied cisTopic to cell populations that are biologically complex, such as the cells present in the mammalian brain. Not only did cisTopic allow them to recover the major cell types in the brain, but the team was also able to identify new subpopulations and master regulators of neuronal cell types.

"In addition to the brain, we also used cisTopic to investigate dynamic changes in gene accessibility in melanoma cell cultures from patients," adds Aerts. "When we modulated one of the known important modulators in these cancer cells, we could for the first time track changes in the accessibility of different DNA regions over time. Such approaches will finally allow us to better understand what these master regulators actually do in cancer cells, and which genes they control."

These different applications illustrate the value of the team's new method for studying the players and mechanism that orchestrate gene regulation in our cells. According to computational biologists like Aerts, this is an important step towards real-time and personalized monitoring of cell states in health and disease.
-end-
Publication

cisTopic: cis-Regulatory topic modelling on single-cell ATAC-seq data, Bravo González-Blas, Minnoye et al. Nature Methods

Questions from patients

A breakthrough in research is not the same as a breakthrough in medicine. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years. This can raise a lot of questions. That is why we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: patienteninfo@vib.be?. Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.

VIB (the Flanders Institute for Biotechnology)

Related Cancer Cells Articles:

Scientists have identified the presence of cancer-suppressing cells in pancreatic cancer
Researchers have identified cells containing a protein called Meflin that has a role in restraining the progression of pancreatic cancer.
Changes in the metabolism of normal cells promotes the metastasis of ovarian cancer cells
A systematic examination of the tumor and the tissue surrounding it -- particularly normal cells in that tissue, called fibroblasts -- has revealed a new treatment target that could potentially prevent the rapid dissemination and poor prognosis associated with high-grade serous carcinoma (HGSC), a tumor type that primarily originates in the fallopian tubes or ovaries and spreads throughout the abdominal cavity.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
White blood cells related to allergies may also be harnessed to destroy cancer cells
A new Tel Aviv University study finds that white blood cells which are responsible for chronic asthma and modern allergies may be used to eliminate malignant colon cancer cells.
Conversion of breast cancer cells into fat cells impedes the formation of metastases
An innovative combination therapy can force malignant breast cancer cells to turn into fat cells.
More Cancer Cells News and Cancer Cells Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...