Posts (17)

1 day ago · Mayo researcher secures NIH grant to advance care of rare disease

Eva Morava-Kozicz, M.D., Ph.D. received a $5 million grant from the National Institutes of Health to study frontiers in congenital disorders of glycosylation (CDG). These disorders often cause serious, sometimes fatal, malfunction of several different organ systems in affected infants.

“This grant will allow us to leverage cross-disciplinary, team-based clinical science to address decades of unresolved questions, increase clinical trial readiness, advance and share knowledge, develop treatment, and meet unmet patient needs,” says Dr. Morava-Kozicz.

Dr. Morava-Kozicz conducts translational research in congenital disorders of glycosylation and mitochondrial disorders and is actively involved in developing dietary therapies in genetic disorders. In addition to her roles as a pediatrician, geneticist and metabolic specialist, she has decades of experience in the diagnostics, follow-up and treatment in inborn errors of metabolism, especially congenital disorders of glycosylation and in mitochondrial disorders.

As principal investigator of the multicenter study on the natural history of congenital disorders of glycosylation, Dr. Morava-Kozicz knows first-hand what gaps need to be addressed.

In response to this need Dr. Morava-Kozicz established a nation-wide network of 10 regional centers to:  

  • Define the natural history, validate patient reported outcomes and share CDG knowledge
  • Develop and validate new biochemical diagnostic techniques and therapeutic biomarkers to increase clinical trial readiness
  • Evaluate whether dietary treatments restore appropriate glycosylation to improve clinical symptoms and quality of life

The grant supports the new Frontiers in Congenital Disorders of Glycosylation consortia, through the Rare Diseases Clinical Research Network (RDCRN), aimed at fostering collaborative research among scientists to better understand how rare diseases progress and to develop improved approaches for diagnosis and treatment.

Congenital disorders of glycosylation are a group of over 150 inherited metabolic disorders affecting several steps of the pathway involved in the glycosylation of proteins. They typically present as multi-systemic disorders with a broad clinical spectrum including, but not limited to, developmental delay, an abnormally low level of muscle tone, abnormal magnetic resonance imaging findings, skin manifestations, and hemorrhaging or clotting disorders. Neurological abnormalities may also be present. There is considerable variation in the severity of this group of diseases ranging from a mild presentation in adults to severe multi-organ dysfunctions causing infantile death.

An important focus of the award is on clinical trial readiness. In order to be prepared to conduct clinical trials the consortia needs to have strong natural history studies that show how the disease progresses. This will lead to ways to measure outcomes of treatments and biomarker studies that provide indicators of how a drug is working in patients.

Collaboration is key. The consortium includes numerous partner research teams from different sites, along with rare disease patients and advocacy groups as research partners. Scientists from different institutions will come together to share patients, data, experience and resources.

Investigator partners include Children Hospital of Philadelphia, Seattle Children’s and Sanford Burnham Prebys Medical Discovery Institute.

Co-investigators include Baylor College of Medicine; Boston Children’s Hospital; Children’s Hospital of Colorado; Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center; National Human Genome Institute; Seattle Children’s Hospital; Tulane University Medical School; University of Alabama; University of Colorado, University of Minnesota Masonic Children’s Hospital; and University of Utah.

Wed, Sep 11 10:51am · Improving genomic data analysis - from soybeans to humans

Article by Colette Gallagher and Amy Clay-Moore

Daniel Wickland, Ph.D.

When Daniel Wickland,
Ph.D., was a predoctoral student at the University of Illinois at
Urbana-Champaign, he first worked to improve genomic data analysis for soybeans.
But soon he shifted his focus, bringing his computer programming and
informatics skills to work with Mayo Clinic and Illinois researchers to better
understand Alzheimer’s disease as part of the Mayo
Clinic and Illinois Alliance for Technology-Based Healthcare Research
Fellowship program
. Now he’s joined Mayo Clinic’s Department
of Health Sciences Research, applying his skills to help better understand the
underlying mechanisms driving breast cancer and to help develop immune-based
cancer therapies.

Here’s a closer look at how Daniel’s research fellowship led him to his new role at Mayo Clinic.

A program to distinguish genomic differences  

During the first part of his graduate program, Daniel worked with Illinois crop sciences professor Matthew Hudson, Ph.D., to map a gene in soybeans that controlled plant height and internode length.

Early in the project, the
team discovered the software they were using was not accurately identifying
differences between soybean genomes. While seeking a solution, Wickland
developed GB-eaSy, a program that dramatically increased the accuracy, speed,
and simplicity of genotyping-by-sequencing data analysis.

When Hudson encountered a similar data analysis need in his research at the National Center for Super Computing Applications (NCSA), he immediately thought of Wickland’s work with soybean genomes.

“As a result of Dan’s
prior work on variant calling software, and his interest in neuroscience from
his undergraduate days in the Illinois Neuroscience Program, I thought he would
be an excellent candidate for the Alzheimer’s disease sequencing project,” says
Hudson. “Although soybeans and humans are very different, the bioinformatics
problems involved were closely related,” says Hudson.

Hudson’s work with Liudmila
Mainzer, Ph.D
.,
senior research scientist at NCSA, and Yan
Asmann, Ph.D
.,
associate professor of biomedical informatics at Mayo, focused on improving genetic
variant calling software for human genomics targeted at Alzheimer’s disease.

The collaborators used
Blue Waters, NCSA’s petascale computer, to perform a vast number of comparisons
to troubleshoot the huge amount of genome data that Mayo was analyzing on
Alzheimer’s disease.

Although Wickland was nearing completion of his doctoral degree in crop sciences, he decided to transfer to the Informatics Ph.D. program and join this new project to focus on bioinformatics.

In the first year of his fellowship at NCSA, Wickland developed skills in high-performance computing and workflow programming. He mastered the complex workflows on Blue Waters necessary to analyze the data in several ways to determine the source of inconsistencies they were finding.

Over two years, the project used more than 600,000 node hours on Blue Waters, which is equivalent to a single server running continuously for almost 100 years.

“These intensive computing needs could not have been met without a resource like Blue Waters at NCSA” says Wickland. “Also critical to the success of this project were feedback and ideas from Dr. Hudson and Dr. Mainzer, my advisors at NCSA.”

Collaborating with Mayo Clinic experts to refine data analysis

In his second year,
Wickland worked at the Mayo Clinic campus in Florida and with Illinois
researchers to analyze genomic sequencing data of more than 10,000 cases and
healthy controls from the project.

“I received invaluable
guidance from my Mayo advisor, Dr. Asmann, and very helpful feedback from
renowned Alzheimer’s researchers at Mayo,” notes Wickland. “Working in these
two environments – Mayo Clinic and NCSA – exposed me to different methods and
ideas that strengthened my skills as a researcher.”

“He was ultimately able to determine that in this case, the problem did not lie in the software itself, but in the discrepancies between the data generated at the different participating institutions in the project,” says Hudson.

A new role

After receiving his doctoral degree, Wickland joined the Mayo Clinic Department of Health Sciences Research. He is working on a project that focuses on breast cancer immunogenomics with Dr. Asmann, Keith Knutson, Ph.D., professor of immunology, and Mark Sherman, M.D., professor of epidemiology and laboratory medicine and pathology.  

“I’m currently studying how the immune system
responds to tumor neoantigens (protein fragments found only on the surface of
cancer cells), how this response differs among individuals and among racial
groups, and how we can use this information to predict and enhance the
anti-tumor immune response in a personalized manner. This genomics research will
support efforts in the Center
for Individualized Medicine
to develop customized cancer vaccines targeted
to the specific neoantigens produced by a patient’s tumor,” says Dr. Wickland.

The Mayo-Illinois Alliance for Technology-Based Healthcare was founded in 2010 by Mayo Clinic and the University of Illinois – Urbana Champaign to advance research and clinical treatment options related to individualized medicine.

The latest advances in cancer care

Join us for Individualizing Medicine 2019 Conference: Precision Cancer Care through Immunotherapy and Genomics on Sept. 20-21, in Scottsdale, Arizona. 

The conference brings together experts from Mayo Clinic and across the country to present and discuss case-based approaches to using genomics and new immunotherapies that oncologists and their teams can bring back to their own patients.

Other key conference themes include:

  • CAR-T cell therapy
  • Clonality
  • Pharmacogenomics
  • Lineage Plasticity
  • National Cancer Institute match

Preview the conference program.

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Wed, May 15 8:00am · One year in, All of Us Research Program makes strides in diverse health research

All of Us Research Program Group

For far too long, biomedical research has been based on a small subset of the United States population, leading to prevention and treatment methods that are often one-size-fits-all. To address this issue, the National Institutes of Health All of Us Research Program is working to build a cohort of one million or more participant partners that reflects the diversity of the United States.

Program participants provide data and samples that will be broadly accessible to researchers for a wide range of studies. By taking into account individual differences, researchers will uncover paths toward delivering precision medicine — or individualized prevention, treatment, and care — for all of us.

May 6 marked one year from the program’s national launch. A Facebook live session,  “From Data to Discoveries: Creating a Research Program for All of Us,” was hosted by Francis Collins, M.D., Ph.D., director, National Institutes of Health. Dr. Collins identified the building blocks of a meaningful research program, including an engaged and diverse participant community, and forecasted the program’s scientific possibilities.

1st Year Milestones – All of Us Research Program Biobank at Mayo Clinic

Mayo Clinic is one of more than 100 organizations across the United States that is funded by the National Institutes of Health All of Us Research Program. In 2016, Mayo Clinic was awarded $142 million in funding over five years by the National Institutes of Health to serve as the program’s biobank.

“The All of Us Research Program biobank at Mayo Clinic has the capacity to store more than 35 million biospecimens.”

Since the launch of the program on May 6, 2018 several milestones have been reached.

“The All of Us Research Program biobank at Mayo Clinic has the capacity to store more than 35 million biospecimens,” says Stephen Thibodeau, Ph.D., co-principal investigator of the All of Us Research Program biobank funding award. “It is currently storing more than 3 million frozen vials from consented participants and has capacity to process samples from up to 1,500 participants per day.”

In addition to increasing lab space in Rochester and on the Mayo Clinic campus in Florida, the team ramped up equipment, built up its technical infrastructure, and has established a business continuity plan in the case of a catastrophic event.

“We expanded our laboratory operation to fully automate sample processing and sample storage,” says Mine Cicek, Ph.D., co-principal investigator and laboratory director, Mayo Clinic Biorepositories Program, Center for Individualized Medicine. “Our team continually monitors multiple indicators related to incoming specimen quality control events and provides feedback to enrollment sites.”

From hiring support staff to maintaining an education plan for program partners to providing 24/7 customer support the All of Us Research Program Biobank at Mayo Clinic works to enable precision medicine research to improve the health of the nation.

More information

For more information, visit the All of Us Research Program website.

Watch the Facebook Live session celebrating the program’s one-year mark and hear from National Institutes of Health Director Francis Collins, M.D.:

Dr. Thibodeau is the David F. and Margaret T. Grohne Director, Mayo Clinic Biorepositories Program, Center for Individualized Medicine.
This work is supported under NIH funding award RFA-PM-16-004. 

“All of Us” is a registered service mark of the U.S. Department of Health and Human Services. For more information, visit http://www.JoinAllofUs.org and http://www.allofus.nih.gov.

Tue, Apr 23 10:07am · Editorial: Why DNA sequencing is an effective tool for patient care

By Keith Stewart, M.B., CH.B.

For the past 30 years, I’ve been fortunate enough to work with and help many patients. But over that time, I’ve also met people who did not respond to therapy or had significant side effects, while others had marvelous responses. Cases like these show a clear need for personalized medicine. Fortunately, I’ve also seen the adoption of a new technology that allows us to gain unprecedented insight into a patient’s specific needs: DNA sequencing.

Dr. Keith Stewart, Medical Director, Mayo Clinic Center for Individualized Medicine
Dr. Keith Stewart

Everyone has their own unique sequence of DNA — a molecular fingerprint — that determines personal characteristics like height, hair and eye color, and risk for disease. Research has shown us that insights into a person’s DNA sequence allows us to personalize their health care to their own genetic makeup to better meet their needs.*

In the past decade, we’ve seen exponential growth in DNA sequencing technology and an expansion of its use in medicine.* In 2012, Mayo Clinic adopted DNA sequencing as a major tool in individualized medicine by using targeted gene panels and whole exome sequencing. We started by looking for actionable targets in patients with advanced cancers (unique features of a tumor that can make one therapeutic drug particularly effective). We quickly expanded this approach beyond cancer by opening clinics that helped to diagnose rare and undiagnosed diseases.

Rare and undiagnosed diseases

Our patients come from around the world, often seeking a diagnosis for a rare disease that no other doctor or clinic has been able to provide. Whole exome testing sequences more than 20,000 genes. That represents about one percent of a patient’s DNA — the part that we today understand contains the majority of useful genetic information that can pinpoint an illness. Patients can get their DNA mapped and have results within a few weeks to apply to their treatment plans. Prenatal screening could be made less invasive and more comfortable for patients with DNA sequencing, so we did that too. What we found was that DNA sequencing greatly expanded our ability to help patients by providing them with more informed and often more effective health care.

Treatment of cancers

One area where we’ve found DNA sequencing to be particularly effective is in the treatment of cancers.* One example that comes to mind is that of a young girl who had acute lymphoblastic leukemia, an aggressive form of blood cancer. None of the mainline therapeutic strategies had worked for this patient. But thankfully, DNA sequencing identified mutations in the cancer that could be leveraged. It’s clear from this example — and from many more like it — that DNA sequencing is a valuable tool in designing personalized treatments for some cancer patients. But there’s also benefit in potentially preventing the development of cancer in the first place. It’s estimated that between 10-15% of cancers involve a heritable mutation.* Current screening methods used to identify people who are at risk of developing cancer may miss up to 50% of heritable cancers. That leaves a lot of room for improvement, and DNA sequencing is proving to be a valuable tool in this regard.

Prevention of adverse drug reactions

Another valuable application is in the prevention of adverse drug reactions. It’s probably no surprise to learn that some people respond to medicine differently compared to others. In some of these cases, people may even have an unwanted or dangerous response to the drug. These are known as adverse drug reactions, and it’s estimated that approximately 1.5 million of them happen each year in the U.S., resulting in a thousand deaths annually. Research has shown us that some people are genetically predisposed to experiencing an adverse drug reaction, which means there’s an opportunity for DNA sequencing to help identify those individuals and help guide their treatment away from unnecessary risks.

My personal experience

It so happens that I’m one of those individuals. Through DNA sequencing, I found that I should avoid a number of medicines. Most of them are drugs that I will probably never need, but some of them I might. Thanks to this testing, I know what those are and can act accordingly in the future. This brings me to a benefit of DNA sequencing that I think we often overlook. I had my DNA sequenced and got information about my carrier status, potential drug reactions, and a number of health conditions. This was important to me because I have family members whose lives have been affected by a heritable genetic condition. I’ve found that having my DNA sequenced empowers me with knowledge — knowledge that I can use in the future to help guide medical treatment away from potentially dangerous drugs, and maybe even help my health care providers save valuable time if they’re ever looking for a diagnosis. So it’s not just a result that helps me stay informed today; it’s something I will likely use for the rest of my life. To be sure, DNA sequencing is not without its limitations.* When we first started in 2012, we were limited by the cost of sequencing and the time it took to receive and interpret a patient’s results. There is still so much we don’t know about genetics, and research is ongoing to determine how DNA sequencing is best applied. But this research has unlocked new avenues for improving outcomes in recent years, and I strongly believe this trend will continue. In the midst of this DNA sequencing revolution, I’ve had the unique opportunity to explore the field as a researcher, a physician, and an administrator, and I can tell you what an exciting time this is to be learning more about your genetics. My experience has shown me that DNA sequencing is not just a thing of the future — it’s a very real and impactful tool of the present.

Keith Stewart, M.B., CH.B., is the Carlson and Nelson Endowed Director of the Mayo Clinic Center for Individualized Medicine.

1. Manolio, Teri A. et al. “Implementing Genomic Medicine in the Clinic: The Future Is Here.” Genetics in Medicine 15.4 (2013): 258–267. PMC. Web. 21 Sept. 2018.   6. https://www.cancer.gov/about-cancer/causes-prevention/genetics

2. Delaney, Susan K. et al. “Toward Clinical Genomics in Everyday Medicine: Perspectives and Recommendations.” Expert Review of Molecular Diagnostics 16.5 (2016): 521–532. PMC. Web. 21 Sept. 2018.

3. Bryce, Alan H., et al. “Comprehensive Genomic Analysis of Metastatic Mucinous Urethral Adenocarcinoma Guides Precision Oncology Treatment: Targetable EGFR Amplification Leading to Successful Treatment With Erlotinib.” Clinical Genitourinary Cancer, vol. 15, no. 4, 2017, doi:10.1016/j.clgc.2016.11.001.

4. Torkamani, Ali et al. “High Definition Medicine.” Cell 170.5 (2017): 828–843. PMC. Web. 21 Sept. 2018.

5. Borad, Mitesh J. et al. “Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers.” Scientific Reports 6 (2016): 25. PMC. Web. 21 Sept. 2018.

6. https://www.cancer.gov/about-cancer/causes-prevention/genetics

Mon, Apr 8 8:00am · Genetic test solves mystery of family bleeding disorder

The Riggs family had a bleeding disorder that spanned three generations and affected the health of multiple family members. They never knew the cause of it, the long term risks associated with it, or the impact it may have on future generations — until a genetic test revealed the answer.

Finding the clues to the mystery of the family bleeding disorder began when Mallory’s father, Timothy, came to Mayo Clinic for cardiovascular surgery. Before surgery he met with Mrinal Patnaik, M.B.B.S., a Mayo Clinic hematologist, specializing in the diagnosis, treatment and prevention of blood diseases.

“I looked at his medical records and it didn’t make sense,” says Dr. Patnaik. “I told him we didn’t know what exactly he had but the fact that three generations in his family all have abnormally low blood platelets makes this very likely to be something inheritable.”

Dr. Patnaik ordered a whole exome sequencing test for Timothy and Mallory. Whole-exome sequencing tests more than 20,000 genes. That represents about one percent of a patient’s DNA – the part containing the majority of useful genetic information that can pinpoint an illness.

The test showed that Timothy and Mallory had a genetic variation in a gene called RUNX1 causing them to have an abnormally low blood platelet count (thrombocytopenia). Some symptoms of a low blood platelet count may include easy or excessive bruising, superficial bleeding, and prolonged bleeding.

“This gene mutation not only causes low blood platelets, but increases the risk for certain blood cancers to develop overtime like myelodysplastic syndrome and acute myelogenous leukemia,” says Dr. Patnaik.

According to Mallory having the answers put her at ease in caring for her son Sawyer who was diagnosed with the same bleeding disorder at 10-months-old. Today, Sawyer is five-years-old and the busiest and most active of her three boys.

“Now that we have answers I can let Sawyer be himself, and be that active little boy and do all of the things that he loves and enjoys doing,” says Mallory. “We can let our kids be kids, wrestling , playing and climbing and not being so concerned about all of the what ifs.”

According to Dr. Patnaik, a genetic test for this family was valuable in finding the answer and providing hope to the family.

“Having a correct diagnosis impacts the family’s medical care today and in the future,” says Dr. Patnaik. “We now understand how to treat them for surgeries, the family has a screening tool and we are monitoring them annually.”

Patients like the Riggs family with rare and undiagnosed conditions can spend years meeting with multiple health care providers to seek a diagnosis. They often try a myriad of treatment plans that aren’t appropriate and never find the answer to what is causing their disorder.

Helping find the answer for the Riggs family inspired Dr. Patnaik to start the first-of-its-kind Premyeloid and Bone Marrow Failure Disorder Clinic so other patients could benefit from precision diagnosis and new individualized therapies.

Mayo Clinic Premyeloid and Bone Marrow Failure Disorder Clinic

  • Offers genetic testing for the early detection of rare blood disorders and bone marrow cancers
  • Uses DNA sequencing and conducts research to solve cases with unexplained low blood counts
  • Allows for early intervention in which providers can define disease management plans
  • Identifies through research how each patient’s unique genetic makeup impacts these disorders and could lead to new individualized therapies

For more information visit ClinicalTrials.gov.

  • Search for NCT02958462 or via Google by title.
  • The clinical service and the NIH-listed research study will appear.
  • Patients can have the clinical service without doing any research.

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Mon, Jan 14 7:00am · Using brain organoids to uncover causes of neuropsychiatric disorders

Mayo Clinic and Yale University collaborated in a study published in Science to create a new model for studying neuropsychiatric disorders in early human brain development. This unique collaboration brought together Mayo Clinic’s team-based, patient-centered research with Yale researchers to discover and analyze the genetic mechanisms that may cause these disorders.

The Mayo Clinic team, led by biomedical scientist Alexej Abyzov, Ph.D., used the organoid model to analyze artificially grown cells that resemble the brain (brain organoids) to outline groups of developmental genes and regulatory elements related to the cause of autism.

Researchers know that genes implicated in neuropsychiatric disorders are active in the human fetal brain. However, systematic and comprehensive studies are hampered due to the difficulty in getting fetal brain tissue. According to Dr. Abyzov, the power of organoids is that they can be created from the skin cells of any individual.

“Using brain organoids helps to uncover the genetic underprints of these disorders and helps identify functional elements that may drive disease onset,” says Dr. Abyzov. “Our results suggest that organoids may reveal how noncoding mutations contribute to the cause of autism. By understanding the cause of autism this research may lead to assessing the personal risk for other neuropsychiatric disorders.”

The research team set out to discover gene-regulatory elements and chart their dynamic activity during prenatal human brain development, focusing on enhancers (the short region of DNA), which carry most of the weight upon regulation of gene expression.

“Over a period of time we modeled human brain development using human-derived brain organoids and compared those organoids to fetal brain tissue that had the same genotype,” says Dr. Abyzov. “This study validated that using brain organoids is a suitable model system for studying gene regulation in human embryonic brain development, evolution and disease.”

The research team is planning a larger study using organoids to compare regulation and expression during development for individuals with autism.

“This model has the potential to offer a personalized approach to each patient with autism,” says Dr. Abyzov.

Dec 24, 2018 · The priceless gift of knowing your family health history

With New Year’s resolutions right around the corner, it is likely one of your resolutions will be focused on your health. Most of us want to eat healthier foods, exercise more, lose weight, and reduce stress.
But, have you ever considered diving deeper into understanding your health conditions and how your DNA—your very own genetic fingerprint—can impact them? If so, this is an opportune time as you gather with family, to begin creating a family health history.

Begin by looking for common threads that may indicate the potential presence of a genetic variant that’s been passed down from one generation to the next in a family. To start, it’s useful to know if anyone on either side of your family has had a major medical condition, at what age it was diagnosed, how it was diagnosed, by whom it was diagnosed, and how it was treated. Drawing family trees can help you keep track of this information (trees can be compiled by using tools like the pedigree tool, such as this one found in Mayo Clinic GeneGuide™. MayoClinic GeneGuide™ is a laboratory DNA test that you can do in your own home through a saliva collection test that is mailed in for results. Consider adding information about each person, such as, current health status, age, and other details. By adding important information about each of your relatives, you are creating your family history.

Today, DNA sequencing and a detailed family medical history are often used together to help people understand their chances of developing or passing on a hereditary disease. For many people, keeping track of their family’s medical history is simply a precaution, and there are often no clues that raise concern. But for some, it can be life-changing. Research has shown that several types of cancer and heart disease could be detected and, in some cases, even prevented if those at risk are identified early.

Some warning signs of a potential disease-causing genetic variant within a family include:
○ Onset of disease at an earlier age than average
○ Family history of the same disease multiple times in multiple relatives (e.g., multiple relatives diagnosed   with an irregular heart beat)
○ Personal and/or family history suggestive of a medical syndrome (e.g., colon and uterine cancer in the same side of the family can indicate the family is at an increased odds to have Lynch syndrome)
○ Personal and/or family history of a diagnosis of a rare disease

Although DNA sequencing is a powerful way to identify individuals at risk of developing a disease, collecting family history information is still an important practice. The Centers for Disease Control advises that people collect family history information whenever possible.

Talking with your family may give you new insights into your health and what’s in your genes.
To learn more about a genetic testing experience that helps you understand how genetics can affect your heath visit Mayo Clinic GeneGuide.

Disclosure: Mayo Clinic has a financial interest in Helix.

Nov 12, 2018 · Novel data-driven approach for precision medicine

Thousands of patients’ tumors have been sequenced in the past decade, yielding a rich source of data on the changes associated with the cancer development and treatment response. However, there are no validated methods that are used in the clinic to select the best therapy. Today, Mayo Clinic researchers report an omics-guided (comprehensive) drug prioritization method tailored to an individual cancer patient.

“To date, genomic sequencing data provided to clinicians includes information on a small set of gene alterations. Recommendations for therapy do not account for many other genomic and clinical factors that might dictate tumor response,” says Mayo researcher Krishna Rani Kalari, Ph.D. “Therefore, there is an urgent need for a comprehensive approach to integrate an individual’s clinical, germline and tumor genomic data to identify and select the best treatment for a patient.”

Dr. Rani Kalari, a computational biologist, and lead author of a Mayo Clinic led study, published in JCO Clinical Cancer Informatics showed that combining multiple sources of data to predict the most effective drug choices for patients with cancer is feasible.

“We developed PANOPLY- Precision cancer genomics report: single sample inventory, an open-source computational framework to analyze complex multidimensional data to determine the most appropriate drug to target an individual’s tumor,” says Dr. Kalari. “PANOPLY approach is more comprehensive and efficient than existing single-sample analyses methods,” says Dr. Kalari.

PANOPLY includes existing FDA-approved drugs and prioritizes the drugs for patients with cancer-based on their omics profile and reports the results for oncologists to guide treatment decisions. In this study, PANOPLY was applied to in-house breast cancer datasets, and the findings were confirmed with patient-derived xenograft (PDX) models Tissues or cells from a patient’s tumor are implanted into an immuno-deficient mouse. These mouse models are used to create an environment that resembles the natural growth of cancer, for the study of cancer progression and treatment. In addition, the researchers demonstrated the flexibility of the PANOPLY framework by applying it to colon, breast, ovarian and glioblastoma datasets from The Cancer Genome Atlas.

Dr. Rani Kalari is using high-throughput tumor sequence data and teaming up with basic scientists such as Liewei Wang, Ph.D., M.D. director of the Mayo Clinic Pharmacogenomics Program, to determine whether PANOPLY can identify novel drug targets. After successful testing and benchmarking of the method using PDX repositories, they plan to work towards the ability to merge PANOPLY reports into the electronic medical records so the information is available to oncologists.

“Currently, the vast majority of patients with cancer continue to receive treatments that are minimally informed by omics data. Working with Mayo Clinic surgeon Judy Boughey, M.D. and oncologist Matthew Goetz, M.D., we anticipate that the proposed work will open new research and clinical vistas to allow a more individualized approach for the better treatment of patients,” says Dr. Kalari.

Mayo Clinic authors are:

Krishna R. Kalari, Ph.D.

Jason P. Sinnwell

Kevin J. Thompson, Ph.D.

Xiaojia Tang, Ph.D.

Erin E. Carlson

Jia Yu, Ph.D.

Peter T. Vedell, Ph.D.

James N. Ingle, M.D.

Richard M. Weinshilboum, M.D.

Judy C. Boughey, M.D.

Liewei Wang, Ph.D., M.D.

Matthew P. Goetz, M.D.

Vera Suman, Ph.D.

This study is funded in part by the Mayo Clinic Center for Individualized Medicine; Nadia’s Gift Foundation; John P. Guider; the Eveleigh Family; George M. Eisenberg Foundation for Charities; generous support from Afaf Al-Bahar; and the Pharmacogenomics Research Network (PGRN).  Other contributing groups include the U54 GM114838, Mayo Clinic Cancer Center (P30CA 15083-43) and the Mayo Clinic Breast Specialized Program of Research Excellence (SPORE- P50CA116201).

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