A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018, University of Utah
Sean Tavtigian, PhD, a cancer researcher at Huntsman Cancer Institute (HCI) and professor of oncological sciences at the University of Utah. Credit: Huntsman Cancer Institute

Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

The research was led by Sean Tavtigian, PhD, a cancer researcher at Huntsman Cancer Institute (HCI) and professor of at the University of Utah, in collaboration with genetics experts from around the United States.

Tavtigian utilized Bayes' Theorem, a math equation first published in 1763, as the basis of a he and the team developed to assess the rigor of the current, widely-used approach to evaluate the results of a clinical genetic test.

Clinical genetic testing is used in a variety of medical fields, including cancer care, obstetrics, and neurosciences, among others. Results of a genetic test may help to provide a definitive medical diagnosis, or assess the likelihood of a person to develop a particular disease before symptoms appear. The range of approaches employed to provide health care based on the results of the test can vary significantly. Patients may be at negligible risk for disease with no required, or they may pursue costly, invasive medical treatment in an effort to stave off disease or manage and minimize symptoms.

With millions and millions of changes possible in genes that control health in any given person, the challenge of discerning which gene changes are likely to cause disease is vast. In the past few years, human genetic researchers have identified thousands of Variants of Uncertain Significance (VUS), that is, genetic changes without a known understanding of how they may impact a person's health. "A large fraction of VUS are believed to be generally harmless," describes Tavtigian. "One only wants to change the medical management of patients when the genetic testing identifies a variant that is likely to be disease-causing. Against a huge population of harmless VUS, how do you identify the small subset that are likely to require medical management?"

The research team set out to reduce subjectivity or interpretation bias in the review of genetic results to determine whether a patient is susceptible to . Using the computational tool they designed, they tested 18 subjective rules recommended by the American College of Genetics and Genomics (ACMG) in the current framework for assessing results of clinical genetic tests. They found that the ACMG's system of 18 rules is statistically sound and that the rules are objectively strong. Also, the rules generally maintained their relative strength when tested against one another. Further, the team explored ways to allow the framework to continue to be employed as new findings about genetics are added to this body of knowledge.

"The scale of genetic testing used by specialists is growing exponentially, with genetic testing laboratories working to keep up with the demands of processing and interpreting the results of genetic tests," says Tavtigian. "The points of internal consistency that we found did not have to be true—yet they are, and it is important that the community knows this. We hope this work will help accelerate application of results from these tests to make decisions about patient care, adding years to patient's lives."

Explore further: Concerns surround use of direct-to-consumer genetic testing

More information: Sean V Tavtigian et al, Modeling the ACMG/AMP variant classification guidelines as a Bayesian classification framework, Genetics In Medicine (2018). DOI: 10.1038/gim.2017.210

Related Stories

Concerns surround use of direct-to-consumer genetic testing

October 27, 2017
(HealthDay)—Direct-to-consumer genetic testing raises unique concerns and considerations, according to a committee opinion published online Oct. 24 in Obstetrics & Gynecology.

Genomic data sharing is critical to improving genetic health care

January 5, 2017
There are an estimated 5,000 - 7,000 rare genetic diseases, each of which can vary dramatically and be caused by a multitude of different genetic changes. Even common diseases with genetic influences may also have rare variants ...

Recommendations for genetic counseling and genetic testing for hereditary prostate cancer

December 13, 2017
To date, there have been few recommendations to guide physicians about when to offer men genetic consultation for prostate cancer risk. Now, an international and inter-specialty panel of experts convened at the Sidney Kimmel ...

Internists play a vital role in identifying patients for genetic counseling for cancer risk

October 30, 2017
Patients at high risk for familial cancer, history of cancer at a young age, or history of multiple cancer occurrences may be referred to genetic counseling for genetic testing from the primary care office, which makes internists ...

Physicians' misunderstanding of genetic test results may hamper mastectomy decisions

April 12, 2017
A recent survey of over 2,000 women newly diagnosed with breast cancer found that half of those who undergo bilateral mastectomy after genetic testing don't actually have mutations known to confer increased risk of additional ...

CONNECT registry shows only 9 percent compliance with genetic testing guidelines for AML

June 5, 2017
Guidelines by the National Comprehensive Cancer Network (NCCN) recommend testing for seven known genetic changes in patients with Acute Myeloid Leukemia (AML). A study presented today at the American Society for Clinical ...

Recommended for you

RNA thought to spread cancer shows ability to suppress breast cancer metastasis

October 22, 2018
Researchers at The University of Texas MD Anderson Cancer Center have discovered that a form of RNA called metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appears to suppress breast cancer metastasis in mice, ...

New tool gives deeper understanding of glioblastoma

October 22, 2018
Researchers in the lab of Charles Danko at the Baker Institute for Animal Health have developed a new tool to study genetic "switches" active in glioblastoma tumors that drive growth of the cancer. In a new paper in Nature ...

Researchers find common genetic link in lung ailments

October 22, 2018
An international research team led by members of the University of Colorado School of Medicine faculty has identified a genetic connection between rheumatoid arthritis-associated interstitial lung disease and idiopathic pulmonary ...

A single missing gene leads to miscarriage

October 19, 2018
A single gene from the mother plays such a crucial role in the development of the placenta that its dysfunction leads to miscarriages. Researchers from the Medical Faculty of Ruhr-Universität Bochum (RUB) have observed this ...

Making gene therapy delivery safer and more efficient

October 18, 2018
Viral vectors used to deliver gene therapies undergo spontaneous changes during manufacturing which affects their structure and function, found researchers from the Perelman School of Medicine at the University of Pennsylvania ...

Student develops microfluidics device to help scientists identify early genetic markers of cancer

October 16, 2018
As anyone who has played "Where's Waldo" knows, searching for a single item in a landscape filled with a mélange of characters and objects can be a challenge. Chrissy O'Keefe, a Ph.D. student in the Department of Biomedical ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.