Corporate Banner
Satellite Banner
Proteomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Connecting the Genetic Dots of Disease

Published: Friday, November 09, 2012
Last Updated: Friday, November 09, 2012
Bookmark and Share
Broad Institute scientists aim to understand the underlying biology leading to disease.

When Liz Rossin began the PhD portion of the Harvard/MIT MD-PhD program in the lab of Mark Daly, a ubiquitous and critical problem in genetic research caught her attention. At the time, researchers had identified more than 150 genetic regions scattered throughout the genome tied to various diseases. Such experiments, known as genome-wide association studies (GWAS), would turn up dozens of regions likely harboring genetic changes contributing to risk of disease, but would not point to specific causal mutations. In order to understand the underlying biology leading to disease, Rossin and her colleagues wanted to identify the connections among these regions.

“That’s the problem we were interested in,” says Rossin, who is now finishing medical school at Harvard. “We have all of these regions in the genome associated with disease, but we don’t necessarily know what they mean or what they have to do with one another.”

Inspired by this challenge, Rossin went on to create DAPPLE – Disease Association Protein-Protein Link Evaluator – an algorithm that can help researchers examine possible networks and draw meaningful conclusions from GWAS data by looking at the physical interactions among proteins. DAPPLE has been used to evaluate data for a variety of diseases including Alzheimer’s disease, rheumatoid arthritis, autism, and more.

Most recently, Broad researchers and collaborators used DAPPLE in a study of inflammatory bowel disease, an illness that includes Crohn’s disease (CD) and ulcerative colitis (UC), both inflammatory diseases of the gastrointestinal tract (a paper detailing the results was published in Nature this week – you can check out a Broad press release here or the original paper here). By combining raw data from studies of CD and UC and adding newly collected genetic information, the team was able to more than double the number of genetic regions tied to disease. To draw conclusions from these 160 genetic results, the researchers turned to DAPPLE.

“DAPPLE is a powerful tool for this kind of project,” says Stephan Ripke, one of the first authors of the Nature paper and a researcher at the Broad Institute and Massachusetts General Hospital. “It allows you to build networks and then determine which of those networks make the most sense.”

DAPPLE is a tool of permutation, meaning that it takes proteins in protein-protein interaction databases and rearranges them again and again so that when researchers build a network – say, from 160 regions of the genome tied to IBD – they can compare it to what would be expect by random chance. When Rossin created DAPPLE in Daly’s lab, she teamed up with Kasper Lage, now a researcher at the Broad Institute, and Chris Cotsapas, now an assistant professor at Yale, to populate the algorithm with a list of hundreds of thousands of known protein-protein interactions. Rossin describes these interactions as the “workhorses of the cell” that set off important physical and chemical reactions. DAPPLE uses these known interactions to test possible networks and even predict new associations. In the case of IBD, DAPPLE helped the researchers narrow in on a protein network that implicated genes known to influence how the body responds to pathogens that cause diseases like tuberculosis and leprosy.

“DAPPLE will make an educated guess about all of the genes in a region that could be playing a role in disease, and it will do it for each region, and then ask if the network that it has generated is more connected than would be expected by random chance,” Rossin explains. “If the answer is yes, it will tell you which genes are driving that connection.”

Researchers can then follow up on these critical, driving genes. In previous studies of autism, DAPPLE turned up hits in pathways involved in chromatin remodeling.

“With DAPPLE, you can go from a big list of regions to a narrowed down list of genes that may be very important for your disease,” says Rossin.

Rossin has been impressed by the many uses researchers have found for the algorithm she helped create, several of which she could not have envisioned when DAPPLE was originally built.

“When we created DAPPLE, we wanted to make the tool as accessible as possible, so we built a website that anyone can use – you don’t even have to download it,” she says. “It’s been really exciting for me to see the way people have started using it.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More than 4,800+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

A Cellular Symphony Responsible for Autoimmune Disease
Broad Institute researchers have used a novel approach to increase our understanding of the immune system as a whole.
Monday, November 30, 2015
Two Studies Identify A Detectable, Pre-Cancerous State In The Blood
Findings pave way for new lines of cancer research focused on detection and prevention.
Thursday, November 27, 2014
Understanding Triglycerides’ Role in Coronary Disease
The study leverages new genetic data from a related genome-wide association study, suggests that lowering triglyceride levels through treatment may help reduce the risk of coronary heart disease.
Wednesday, October 09, 2013
Better Living through Proteomics
As a patient facing illness, knowing what’s ailing you can bring peace of mind and, more importantly, can inform treatment decisions.
Monday, September 09, 2013
Putting Proteins in their Place
Finding and mapping the human proteome can be a drawn-out and tricky process.
Monday, February 18, 2013
Target Set on Cancer Gene MCL1
Broad Institute and Dana-Farber colleagues identify several chemical compounds that tamp down the expression of the MCL1 gene.
Friday, June 15, 2012
Gene Mismatch Influences Success of Bone Marrow Transplants
Missing gene in donor found to increase recipient's chances of graft-versus-host disease, a common complication of bone marrow transplantation.
Monday, November 30, 2009
Scientific News
Liquid Biopsies: Miracle Diagnostic or Next New Fad?
Thanks to the development of highly specific gene-amplification and sequencing technologies liquid biopsies access more biomarkers relevant to more cancers than ever before.
Cell Cargo Ships in Near Future?
Virus-inspired container design may lead to cell cargo ships following construction of ten large, two-component, icosahedral protein complexes.
Protein Reinforces Growth of Damaged Muscles
Biologists have found a protein involved in stem cells that bolsters damaged muscle tissue growth - potential for muscle degeneration treatments.
Structure of Cold Virus Solved
Researchers have identified the structure of an elusive cold virus linked to child asthma and respiratory infections, providing the foundation for treating the virus.
New Protein Model Could Accelerate Drug Development
Stony Brook-led international research team creates ultra-fast approach to model protein interactions.
Researchers Can Control Genes Involved in Cancer
A new way to control the activity of a protein, that is often upregulated in cancer, has been discovered by Moffitt researchers through monoubiquitination mechanism.
Mitochondrial Role in Metastatic Cancer
Researchers have manipulated proteins, sourced from tumour cells, that are essential for maintaining tumour cells and in doing so, have significantly reduced the ability of cancer cells.
Liquid Biopsy Predicts Colon Cancer Recurrence
Scientists have used a genetic test that spots bits of cancer-related DNA circulating in the blood to accurately predict the likelihood of the disease’s return in some — but not all — of a small group of patients with early-stage colon cancer.
Scientists Culture Elusive Yellowstone Microbe
ORNL scientists have successfully isolated and cultured a Yellowstone sourced acidic hot-spring based microbe.
Seeing RNA at the Nanoscale
MIT researchers have developed a new way to image proteins and RNA inside neurons of brain tissue.
Scroll Up
Scroll Down
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!