Translational Omics Program

Genomically powered medicine

An estimated 25 million Americans are living with rare diseases, most of which are genetic and remain undiagnosed. Genomically powered, individualized medicine is transforming how healthcare teams identify, understand and treat these conditions — while also creating new opportunities to prevent disease before it develops.

Advances in state‑of‑the‑art clinical testing are generating unprecedented volumes of genomic data. For many patients, these data provide long‑sought answers to complex diagnostic dilemmas and, in some cases, open the door to novel therapeutic options. At the population level, large‑scale sequencing efforts demonstrate that genomic findings are broadly applicable and highly impactful in clinical decision‑making, enabling more predictive, preventive and precise care. Together, these advances are reshaping patient care and improving lives.

Translational Omics Program

As genomics becomes a standard component of individualized medical care, the challenge has shifted from data generation to data interpretation. The Center for Individualized Medicine established the Translational Omics Program in 2015 to address this critical need by providing deep postanalytical interpretation for omics‑based clinical and translational research.

The program focuses on rare and undiagnosed genetic diseases, populational genomics, and preventive genomic screening. It brings together a multidisciplinary team that integrates computational analysis, data integration and biological interpretation with traditional in vitro and in vivo functional studies, ensuring that complex omics findings can be translated into clinically meaningful insights.

Training the workforce of the future

The Translational Omics Program's core mission is to develop the next generation of translational genomics experts. It offers a rich, collaborative training environment for postdoctoral fellows, graduate students and interns, equipping trainees with skills that span genomics, bioinformatics and clinical medicine. Through this integrated approach, the program is helping build a workforce prepared to translate omics discoveries into patient care.

Translational Omics Program Recharge Facility

The Translational Omics Program provides institutional translational omics interpretive services through its recharge facility, supporting investigators across Mayo Clinic with expert analysis and functional validation of genomic findings.

Through the Translational Omics Program Recharge Facility, program members deliver specialized interpretive and translational services that support both clinical care and research. Team members develop and implement field-leading methods for omics interpretation, combining computational review with laboratory‑based functional studies to facilitate diagnosis, treatment and discovery.

Recharge facility services include:

  • Characterization of variants of uncertain significance and variants in genes of uncertain significance.
  • Execution and interpretation of complementary omics profiling, including RNA sequencing, genome sequencing and methylation sequencing.
  • In silico protein modeling.
  • Functional laboratory studies using cellular and animal models.
  • Identification and development of collaborations and patient cohort studies.
  • Manuscript development and scientific support.

If you are interested in a fellowship or collaboration, please email the Translational Omics Program Recharge Facility at toprf@mayo.edu.

Larval transgenic zebrafish expressing green fluorescent protein in the vasculature and red fluorescent protein in the blood.

Projects

Exome sequencing and genome sequencing have provided diagnostic answers for thousands of patients with rare and undiagnosed diseases and are now widely adopted at institutions around the world, including Mayo Clinic. Despite their impact, current approaches yield diagnoses for only about 30% to 40% of patients, leaving the majority without definitive genetic explanations.

The Translational Omics Program focuses on reevaluating clinically generated sequencing data beyond standard clinical reports. By identifying additional candidate variants and performing targeted follow‑up studies, researchers seek to establish pathogenicity and uncover previously unrecognized genetic causes of disease.

For patients with rare and undiagnosed diseases, the Translational Omics Program employs an integrated, end‑to‑end strategy to maximize diagnostic resolution and enable individualized care.

This work includes systematic reanalysis of existing clinical genomic data as scientific knowledge evolves. Researchers apply complementary genomic, transcriptomic and epigenomic technologies to uncover regulatory and expression‑based disease mechanisms. Then, program members develop scalable, automated approaches for variant interpretation across both individual patients and large populations. They use advanced bioinformatics, structured phenotyping and machine learning methods to connect genetic variation with patient‑specific clinical features, while expanding testing modalities to extend analysis beyond coding regions alone. Finally, the research team further evaluates possible findings through in silico modeling and functional laboratory studies, providing biological validation and mechanistic insight.

Together, these activities transform previously inconclusive results into actionable diagnoses, inform therapeutic strategies, and continuously improve the care of patients with complex genetic diseases.

The RADiaNT project aims to transform care for patients with rare and undiagnosed genetic diseases by integrating complementary RNA sequencing into clinical evaluation. In an initial phase, a subset of successfully diagnosed patients receive personalized antisense oligonucleotide (ASO) therapeutics for evaluation in pilot studies. This work assesses the feasibility of individualized RNA‑based therapies and expands treatment options for patients with rare genetic diseases.

While DNA and RNA sequencing have advanced the diagnosis of Mendelian disorders, some complex cases require deeper insight into epigenetic regulation. Errors in DNA methylation can alter gene expression and contribute to hereditary disease.

To address this gap, researchers are performing methylation sequencing in patients with rare and undiagnosed genetic conditions and integrating these data with existing DNA and RNA results. This comprehensive multi‑omic approach enables more complete molecular characterization and improved diagnostic precision.

Although exome sequencing and genome sequencing have transformed genetic diagnostics, most patients with rare diseases remain undiagnosed or receive results classified as variants of uncertain significance. Meanwhile, new gene‑disease associations are continuously reported in the scientific literature and curated in public databases. The RENEW project uses automated bioinformatics pipelines to identify emerging evidence from major genomic databases and reannotate previously negative or inconclusive exome results. This scalable approach enables rapid reanalysis, allowing unresolved cases to be revisited efficiently as knowledge evolves.

The Translational Omics Program is developing robust annotation frameworks and bioinformatics tools to support large scale population screening initiatives. By leveraging current scientific literature and scalable software solutions, the program enables accurate and efficient interpretation of genetic variation across large cohorts.

Modern genetic testing generates tens of thousands of variants per patient, requiring sophisticated analytics to connect genotype with phenotype. The Translational Omics Program employs intuitive systems to capture clinicians' observations as structured phenotype data, enabling automated analysis and integration with genomic results. The systems cross‑reference these data with scientific literature and biological databases. The research team applies machine learning approaches to prioritize variants most likely to explain a patient's condition.

Beyond short-read DNA sequencing, data from long-read sequencing, RNA, metabolomics and proteomics provide insight into gene structure, activity and regulation. The Translational Omics Program evaluates multi-omic data alongside DNA sequencing to improve diagnostic yield. In a subset of patients, this integrated approach substantially enhances the ability to identify underlying genetic causes of disease.

A major limitation of genetic testing is the prevalence of variants of uncertain significance. To address this challenge, the Translational Omics Program conducts functional studies using protein modeling and experimental systems to evaluate the biological impact of variants. Researchers use genome engineering technologies to introduce patient specific variants into laboratory or animal models, enabling direct assessment of function and supporting more confident clinical interpretation.

Program leaders

  • Jafar Hussain, Ph.D.
  • Deepak Panwar, Ph.D.
  • Arash Salmaninejad, Ph.D.
  • Patrick R. Blackburn, Ph.D.
  • Nicole J. Boczek, Ph.D.
  • Margot A. Cousin, Ph.D.
  • Joe D. Farris, Ph.D.
  • Alejandro Ferrer, Ph.D.
  • Aditi Gupta, Ph.D.
  • Charu Kaiwar, M.D., Ph.D.
  • Erica L. Macke, Ph.D.
  • Joel A. Morales Rosado, M.D.
  • Rory J. Olson, Ph.D.
  • Filippo Pinto e Vairo, M.D., Ph.D.
  • Stephanie L. Safgren, Ph.D.
  • Laura E. Schultz-Rogers, Ph.D.
  • Jan Verheijen, Ph.D.
  • Matheus Wilke, M.D., Ph.D.
  • Nancy William, Ph.D.

Alumni of the Translation Omics Program have successfully completed fellowships in fields such as clinical genetics and oncology, as well as residencies in pathology and related disciplines. Many former fellows and associates now serve in positions such as directors of genetic testing laboratories, clinical variant scientists, academic researchers and a variety of other exciting roles across the industry.

  • Idara U. Ekpoh, M.B.A — Program Manager
  • Courtney B. Graddy, M.H.A. — Program Manager
  • Rory J. Olson, Ph.D. — Clinical Variant Scientist
  • Jennifer Tan-Arroyo, Ph.D. — Clinical Variant Scientist
  • Caer R. Vitek, Ed.D., M.S. — Manager


Publications

Collectively, Mayo Clinic authors publish more than 5,000 articles a year in biomedical journals.

Publishing in medical journals is an expected scholarly activity of professional practice and aligns with our value of sharing expertise and best practices to facilitate the advancement of medical practice worldwide.

Featured research articles

Read peer-reviewed articles about key findings from the Translational Omics Program:

  • Cousin MA, Creighton BA, Breau KA, Spillmann RC, Torti E, Dontu S, Tripathi S, Ajit D, Edwards RJ, Afriyie S, Bay JC, Harper KM, Beltran AA, Munoz LJ, Falcon Rodriguez L, Stankewich MC, Person RE, Si Y, Normand EA, Blevins A, May AS, Bier L, Aggarwal V, Mancini GMS, van Slegtenhorst MA, Cremer K, Becker J, Engels H, Aretz S, MacKenzie JJ, Brilstra E, van Gassen KLI, van Jaarsveld RH, Oegema R, Parsons GM, Mark P, Helbig I, McKeown SE, Stratton R, Cogne B, Isidor B, Cacheiro P, Smedley D, Firth HV, Bierhals T, Kloth K, Weiss D, Fairley C, Shieh JT, Kritzer A, Jayakar P, Kurtz-Nelson E, Bernier RA, Wang T, Eichler EE, van de Laar IMBH, McConkie-Rosell A, McDonald MT, Kemppainen J, Lanpher BC, Schultz-Rogers LE, Gunderson LB, Pichurin PN, Yoon G, Zech M, Jech R, Winkelmann J, Undiagnosed Diseases Network, Genomics England Research Consortium, Beltran AS, Zimmermann MT, Temple B, Moy SS, Klee EW, Tan QK, Lorenzo DN. Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome. Nature Genetics. 2021.
  • Klee EW, Cousin MA, Pinto E Vairo F, Morales-Rosado JA, Macke EL, Jenkinson WG, Ferrer A, Schultz-Rogers LE, Olson RJ, Oliver GR, Sigafoos AN, Schwab TL, Zimmermann MT, Urrutia RA, Kaiwar C, Gupta A, Blackburn PR, Boczek NJ, Prochnow CA, Lowy RJ, Mulvihill LA, McAllister TM, Aoudia SL, Kruisselbrink TM, Gunderson LB, Kemppainen JL, Fisher LJ, Tarnowski JM, Hager MM, Kroc SA, Bertsch NL, Agre KE, Jackson JL, Macklin-Mantia SK, Murphree MI, Rust LM, Summer Bolster JM, Beck SA, Atwal PS, Ellingson MS, Barnett SS, Rasmussen KJ, Lahner CA, Niu Z, Hasadsri L, Ferber MJ, Marcou CA, Clark KJ, Pichurin PN, Deyle DR, Morava-Kozicz E, Gavrilova RH, Dhamija R, Wierenga KJ, Lanpher BC, Babovic-Vuksanovic D, Farrugia G, Schimmenti LA, Stewart AK, Lazaridis KN. Impact of integrated translational research on clinical exome sequencing. Genetics in Medicine. 2021.
  • Blackburn PR, Xu Z, Tumelty KE, Zhao RW, Monis WJ, Harris KG, Gass JM, Cousin MA, Boczek NJ, Mitkov MV, Cappel MA, Francomano CA, Parisi JE, Klee EW, Faqeih E, Alkuraya FS, Layne MD, McDonnell NB, Atwal PS. Bi-allelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome. The American Journal of Human Genetics. 2018.

Citations are from PubMed, a service of the U.S. National Library of Medicine. PubMed comprises references and abstracts from MEDLINE, life science journals and online books:

Find more publications authored by Mayo Clinic experts in the area of translational omics.

Featured blog posts

Read about translational omics breakthroughs and meet our program team on the Center for Individualized Medicine blog:

Multimedia

Molecular Genetics and Genomic Medicine: Margot A. Cousin, Ph.D.

Dr. Cousin discusses her paper, "Pharmacogenomic Findings From Clinical Whole-Exome Sequencing of Diagnostic Odyssey Patients," which was published in Molecular Genetics and Genomic Medicine."

To determine the impact of the secondary pharmacogenomic findings for these patients, we decided to, you know, start this study, which was recently published in Molecular Genetics and Genomic Medicine, and really discusses the pharmacogenetic findings that we found using whole-exome sequencing on diagnostic odyssey patients.

Whole-exome sequencing is a test that looks at all of the genes in your genome. So some of the benefits include, really, not having to know which gene in particular you want to look at.

So we were in the early stages of starting to use exome sequencing for the care of these patients. What we started to realize is that there's other information contained within that no one would really know about unless you're digging through it. Because you get a lot of results back when you get an exome result, right? And within those results, we're starting to find pharmacogenomic variants listed, and of course that wasn't really necessarily related to the disease that we were searching for an answer for, but its an important result that can be used for patients' care.

In looking at our cohort of patients, of the 94 patients we evaluated for pharmacogenomic findings, the majority were young, median age of ten years at testing. The majority also had a neurologic component to their clinical presentation. Seizures was one of the most common phenotypes described in their reason for referral. In the majority of patients had at least on pharmacogenomic variant reported on their clinical WES test, and one fifth of patients were taking a medication at that time that could be impacted by that result.

I think if you look at our patient population, most of the patients were, I think, the average age was about ten years of age. Usually, we don't worry too much about medications when it comes to this population because they are usually not taking a large number of medications. We're usually concerned about a large number of medications in an older population. However, through this study, I came to realize as a pharmacist that pharmacogenomics matters in almost all age groups. Why? Because some of our patients were taking antidepressants. Some of them were taking anti-seizure medications. Some of them were taking pain medications. Some of them were taking muscle relaxants. All these medications, or some of the medications, are metabolized by some the genes that we identified in our cohort. Meaning that pharmacogenomics could, at a certain point, help these patients who are currently taking medications in our population either make changes either with the dose or change the medication to a different medication.

Genetic Testing's Impact on Patient Care — Paige's Story

Whole-exome sequencing probes into a young patient's bone and joint pain.

Individualized Medicine — Javrie's Story

Obscure symptoms are mapped to a rare pediatric disorder.

A Journey of Hope — Karter's Story

RNA sequencing identifies DNA changes that caused genetic irregularities affecting Karter's growth and development.