Informatics for Genetic Sequencing

Overview

the-hard-truth-about-genetics-and-muscle-growthTechnological advances have given researchers and clinicians access to an enormous amount of information about the human genome. Studying the genomes of individuals and populations can help us better understand human health and disease, evaluate factors that modify risk for disease, inform diagnoses, help predict response to treatments, and identify new drug targets.

Given that a person’s genome contains 3 billion bases (DNA building blocks), processing and interpreting the information in even a single individual’s DNA can be a challenge. Interpreting data from multiple genomes collectively raises even more challenges for storing, managing and querying these vast datasets. Researchers at UNC Chapel Hill are attempting to process and analyze genetic information from thousands of individuals, in order to identify patterns and potentially predict variants in genetic disease and response to treatment.

Today, it is relatively easy to sequence a person’s whole genome, but gleaning knowledge from that genetic data which can be used to understand and treat genetic diseases remains challenging. The North Carolina Clinical Genomic Evaluation for NextGen Exome Sequencing (NCGENES) project is a multidisciplinary effort to create a bioinformatics infrastructure and a systematic process for using whole exome sequencing (WES) as a tool in diagnosing disease, revealing genetic markers for disease, and identifying the relationship between a genotype and a disease to identify persons at risk.

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The NCGENES system has thus far conducted WES (exomes are the coding parts of genes that are expressed) on over 800 adult and pediatric patients at UNC Hospitals. The NCGENES system looks for specific genes known to be associated with certain diseases and then scans those genes for mutations that indicate disease or high risk. The data are also scanned for incidental genetic mutations—ones that the researchers weren’t searching for but reveal a previously unknown and treatable condition. Each WES is linked to a patient’s medical records for later re-analysis should new genetic markers be identified. Health care providers receive annotated reports that describe potential genetic links to the patient’s disease phenotype, which is then used to develop individualized treatment plans.

RENCI’s role

RENCI researchers set up a secure database of genetic data that serves as a baseline comparison of each patient’s WES. That database is continuously updated as researchers pinpoint genes that cause disease when mutated. The RENCI team also implemented the analysis system that classifies the genetic data as actionable data that can be used to develop patient treatment plans, un-actionable data when the identified disease has no known treatments, or data that is not yet fully understood. In addition, RENCI developed an automated workflow that tracks a patient’s genetic information from the initial consultation, to genetic sample preparation made at various labs, to high throughput sequencing and data analysis. The system alerts the labs when samples leave one site to head to another and allows researchers to easily locate all samples.

Project Team

  • Kirk Wilhelmsen (Project leader)
  • Chris Bizon, Ph.D
  • Phil Owen
  • Jason Reilly
  • Dylan Young

Partners

Funding

National Human Genome Research Institute

Resources

NCnexus-w-tagline-for-webThe North Carolina Newborn Exome Sequencing for Universal Screening (NCNEXUS) project looks to expand the whole exome sequencing (WES) work achieved in NCGENES to the arena of newborn screening. The goal of WES is to look for specific genes known to be associated with certain diseases and then scan those genes for mutations that indicate disease or high risk. The data are also scanned for incidental genetic mutations – ones researchers weren’t searching for but that reveal a previously unknown and perhaps treatable condition. Newborn screening is currently performed in all 50 states, and while what each state tests for is variable, up to 31 core disorders are routinely tested for in all states. NCNEXUS will evaluate the feasibility of adding WES to extend the utility of current newborn screening. The project will also develop strategies to guide clinicians, clinical laboratories, and patients and families when dealing with incidental findings uncovered through genetic screenings. NCNEXUS will focus on decision making that respects the child and protects his/her future autonomy, while also respecting parental interests and rights.

RENCI’s Role

The RENCI team will develop an automated workflow that tracks a patient’s genetic information from the initial consultation, to genetic sample preparation made at various labs, to high throughput sequencing and data analysis. The system alerts the labs when samples leave one site to head to another and allows researchers to easily locate all samples. The RENCI team will also implement the analysis system that classifies the genetic data based on whether or not a variant has been found and what it could potentially mean.

Project Team

  • Kirk Wilhelmsen (Project leader)
  • Chris Bizon, Ph.D
  • Phil Owen
  • Jason Reilly
  • Dylan Young

Partners

Funding

National Institute of Health (NIH)

Resources

UNC partners with NIH to explore genomic testing for newborns

Recent advances in genomic sequencing technology now make it possible to identify people who unknowingly have rare genetic mutations that dramatically increase their risk of developing serious diseases that can be prevented or ameliorated if detected early.

The Center for Genomics and Society (CGS) at the University of North Carolina at Chapel Hill is funded by the National Institutes of Health to conduct a research project called “GeneScreen,” a screening program to detect medically actionable genetic mutations in adults recruited from primary care providers. CGS investigators (UNC clinicians, geneticists, social scientists, and bioethicists) conducted a systematic, evidence-based review of genetic conditions to target for this genomic screening project. They also consulted with other scientists and community stakeholders to consider the ethical, legal and social issues that are raised by offering such screening. To date, the first pilot phase has recruited 72 UNC participants and 196 participants in the Kaiser Permanente Northwest research biobank, a site where a larger screening program is planned. It is anticipated that screening will improve health outcomes for the small but significant number of people who have these mutations (predicted to be ~1-2% of the general population). We now seek to engage practices through the Practice-Based Research Network of North Carolina, to evaluate GeneScreen in primary care settings beyond the UNC pilot site.

RENCI’s Role

The RENCI team will develop an automated workflow that tracks a patient’s genetic information from the initial consultation, to genetic sample preparation made at various labs, to high throughput sequencing and data analysis. The system alerts the labs when samples leave one site to head to another and allows researchers to easily locate all samples. The RENCI team will also implement the analysis system that classifies the genetic data based on whether or not a variant has been found and what it could potentially mean.

Project Team

  • Kirk Wilhelmsen (Project leader)
  • Gail Henderson, Ph.D
  • Chris Bizon, Ph.D
  • Phil Owen
  • Jason Reilly
  • Dylan Young

Partners

Funding

National Institute of Health (NIH)