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 3,300+ scientific posters on ePosters
  • More than 4,900+ 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
Oxygen Can Impair Cancer Immunotherapy
Researchers have identified a mechanism within the lungs where anticancer immune resposnse is inhibited.
Symmetry is Key to Collagen
Researchers describe how symmetry may be the key to growing collagen fibres outside the body.
Breakthrough in GPCR Understanding
Integral Molecular announces breakthrough in understanding the functionality of GPCRs, the largest class of drug targets in human disease.
Designing Ultrasound Tools with Lego-Like Proteins
Study outlines how ultrasound technology can be used for imaging in conjuction with protein engineering.
Enzyme that Triggers Cell Demise in ALS Identified
Scientists from Harvard have identified a key instigator of nerve cell damage in people with amyotrophic lateral sclerosis (ALS).
Molecular Alarm Clock Wakes Resting Ovules
Study of fruit flies yields discovery of a molecular "alarm clock" that activates resting ovules.
Catching Proteins in the Act
Scientists can now observe light activated processes in proteins through the use of free-electron x-ray lasers.
Proteins Preserve Vital Genetic Data
Research has shown how two key proteins bring about the oragnization of chromosomes and our genome.
Signaling Molecule Regulates Release of the Hunger Hormone Ghrelin
Researchers at UT Southwestern have identified that the blocking release of the hormone ghrelin may mediate low blood sugar effect in children taking beta blockers.
Telomere Replenishment in Real Time
Researchers have visualised the process of telomere attachment to chromosomes through single-molecule imaging.
Scroll Up
Scroll Down
Skyscraper Banner

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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!