Genomics Archives - Sanford Burnham Prebys
Institute News

Genomic study links over 100 genetic positions to metabolite levels

AuthorJessica Moore
Date

March 6, 2017

The largest study yet to examine which genes influence the amount of various metabolites—small molecules that are produced in the course of the body’s constant breakdown and building of other larger molecules—has been published in Nature Genetics. The research, led by Tao Long, PhD, assistant professor at Sanford Burnham Prebys Medical Discovery Institute (SBP), while she was at Human Longevity, Inc. (HLI), linked 101 new sites in the genome to 246 metabolites and uncovered 90 rare variants that lead to abnormal blood levels of certain metabolites.

“This work increases the number of genes known to affect the metabolome—the collection of all of an individual’s metabolites,” says Long. “It also reveals that more rare genetic variants are associated with unusually high or low levels of metabolites than was previously thought.”

Long’s team, directed by Amalio Telenti, MD, PhD, chief scientific officer at HLI, was interested in the metabolome because it reflects what’s going on in the body at any given moment. Changes in metabolite levels could one day be used to diagnose diseases, but for that to be possible, scientists must first understand how the metabolome is influenced by a person’s genes.

The researchers conducted whole genome analysis and comprehensive metabolite profiling on 965 pairs of adult twins (both identical and fraternal). They found that ten percent of the non-related subjects carried rare genetic variants that influence the function of 17 genes. Of these 17 genes, 13 are associated with inborn metabolic errors and other pediatric genetic disorders.   

“Ten percent is a much higher proportion than we expected,” Long adds. “The variations in blood metabolites that we observed could be indicators of health versus disease. Both the metabolic signatures and the rare variants we identified deserve further study.”

This article is based in part on a press release from HLI.

Institute News

Genetic drivers of immune response to cancer discovered through ‘big data’ analysis

AuthorJessica Moore
Date

July 18, 2016

Scientists at the Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified over 100 new genetic regions that affect the immune response to cancer. The findings, published in Cancer Immunology Research, could inform the development of future immunotherapies—treatments that enhance the immune system’s ability to kill tumors.

“By analyzing a large public genomic database, we found 122 potential immune response drivers—genetic regions in which mutations correlate with the presence or absence of immune cells infiltrating the tumors,” said lead author Eduard Porta-Pardo, PhD, a postdoctoral fellow at SBP. “While several of these correspond to proteins with known roles in immune response, many others offer new directions for cancer immunology research, which could point to new targets for immunotherapy.”

Immunotherapy has been heralded as a turning point in cancer because it can treat even advanced cases that have spread to other organs. Several drugs in this class are now widely used and often lead to remarkable success, eradicating or dramatically shrinking tumors and preventing recurrence.

Most current immunotherapies rely on a similar strategy—releasing the brakes on the immune system. These treatments are powerful if the tumor is recognized by the immune system as a threat and allows immune cell infiltration, but some cancers remain undercover or block immune cell entry into the tumor in as yet unknown ways.

“To develop immunotherapies that are relevant to a wide range of cancers, we need to know a lot more about how the immune system interacts with tumors,” said Adam Godzik, PhD, professor and director of the Bioinformatics and Structural Biology Program and senior author of the study. “Our study provides many new leads for this endeavor.”

“We are exploring cancer mutations at fine resolution by accounting for the fact that mutations can affect the encoded protein in different ways depending on where the resulting change is located,” commented Porta-Pardo. “Our algorithm, domainXplorer, identifies correlations between a phenotype, in this case the amount of immune cells in the tumor, and mutations in individual protein domains—parts of a protein with distinct functions.

“This work emphasizes the value of open data,” Godzik added. “Because we could access genomic data from over 5,000 tumor samples from The Cancer Genome Atlas (TCGA), we could jump straight to analysis without having to set up a big collaborative network to gather and sequence so many samples.”

“Our plan for the next phase of this research is to use this algorithm to search for genetic regions correlating with the levels of specific immune cell types within the tumor, which will reveal further details of cancer immunology.”

 

Institute News

Will you be part of the largest-ever clinical research study?

Authorjmoore
Date

March 23, 2016

It’s called the Precision Medicine Initiative (PMI) Cohort Program, and it was just announced in February by President Obama. If you join the cohort (group of subjects tracked over a long period of time), you can help researchers improve precision medicine, in which doctors select the treatments and preventive strategies that will work best for each patient. This program is just one component of the larger Precision Medicine Initiative announced during last year’s State of the Union address.

What’s the goal? According to NIH Director Francis Collins, the cohort program “seeks to extend precision medicine to all diseases by building a national research cohort of one million or more U.S. participants,” all enrolled by 2019.

Why recruit so many people? Since the program is intended to benefit people affected by many diseases and conditions, it must include large, representative samples of people with each type. Large samples increase the likelihood that studies using these data will find new associations and interactions among genes, environmental factors, and disease risk.

What will participants do? Volunteers will share their health records, complete surveys on lifestyle and environmental exposures, undergo a physical, and provide a biological sample (e.g. blood) for genetic testing.

How will people benefit? Participants will be considered partners in research—they’ll have access to their genetic data and, where possible, how their genes, surroundings, and habits affect their health. They’ll also have a say in how the research is conducted and what questions it should address.

Who’s running it? The NIH is overseeing the whole program, but it will be directly run from multiple institutions (which are currently being selected). The pilot phase will be led by Vanderbilt University and Verily (formerly Google Life Sciences).

What’s the cost? $130 million has been allotted in this fiscal year, but more money will be needed to keep the program going.

Should I be excited about it? Maybe. Some leaders in the health field have criticized the program for throwing money at the latest big thing instead of more low-tech problems like unequal access to healthcare, but such a huge data resource is bound to lead to answers to many important questions. 

What are the challenges for the PMI?

  • Scale—The program will generate one of the largest clinical databases yet, and it’s not clear how difficult it will be to make systems that can store and analyze it.
  • Privacy—Data will be anonymized, but keeping the health information of a million people in one place might represent a target for hackers sophisticated enough to figure out participants’ identities.
  • Interoperability—Health record systems are notoriously incompatible with one another. Though the PMI also has provisions to correct this, it likely won’t be a quick fix.

How can I sign up? Enrollment has not yet begun, but the NIH will announce when the public can get involved. So stay tuned…

 

Institute News

Sanford-Burnham at Lake Nona receives Bankhead-Coley grant to expand genomics capabilities

Authorpbartosch
Date

May 6, 2015

The Florida Department of Health recently announced the awardees of this year’s Bankhead-Coley Cancer Research Program grants. Among them is Sanford-Burnham at Lake Nona associate professor and scientific director of Analytical Genomics and Bioinformatics Ranjan Perera, PhD The three-year grant to Perera is valued at almost $1.3 million. Continue reading “Sanford-Burnham at Lake Nona receives Bankhead-Coley grant to expand genomics capabilities”