UF CTSI clinical genomics program
About the Program
The goal of the Clinical Genomics Program is to connect staff, physicians and researchers who seek to apply next-generation sequencing techniques to solve research and clinical questions using a pragmatic and innovative framework that will drive healthcare into the next century.
The potential for discovery and clinical translation is profound – whether exploring the genome of a patient to precisely identify their molecular diagnosis, or documenting population data on genetic variability, disease susceptibility, prognosis, or response to drug treatments the latest advancements in health informatics, data science, and statistical genetics can be used to inform patient treatments.
If you are a clinician or researcher interested in exploring genomic sequencing as an option, please contact us at the email address or telephone number below. Our objective is to help navigate pre-approval for insurance billing, genetic counseling and consent, and subsequent medical genetic consulting. Data generation, alignment, annotation, visualization, and interpretation are to be performed locally, though we also accept data from commercial sequencing providers for re-analysis, annotation, and interpretation. Data is to be made accessible in an ethically responsible manner to enable future research discoveries and clinical genetic correlations.
for a consultation, please contact:
Matthew Farrer, PhD
Program Director and Professor | UF Clinical Genomics Program | Department of Neurology | UF College of Medicine
The program focuses on five central areas or pillars:
Physician teams that order and/or deliver advanced genetic testing to inform patient diagnosis and care
Technologists to that can rapidly generate these results, and the facilities to perform the genotyping/sequencing required
Scientists who can manipulate the data produced, maintain and summarize its variability, and who develop the elaborate network required for data processing, storage and access
Teams who can apply these data sources to improve individualized and/or population health studies
Physicians, residents, researchers, patients and the general public who are interested into training others and engaging in ‘precision medicine’ to enable innovation and scientific discovery
Mission and Vision
Our mission is to generate molecular knowledge, and to decipher, disseminate, synthesize and apply it to fundamentally improve upon the human condition.
Our vision is to improve the health outcomes of patients by interrogating their genomic data to accelerate their diagnosis and target treatments more appropriately. We aim to make genomic sequencing an integrated part of clinical practice and a routine standard of care. To achieve this goal, we are building genomic sequencing and bioinformatics for clinical diagnostics and research and recruiting expertise to enable that expansion. The potential for discovery and clinical translation is profound – whether exploring the genome of a patient to precisely identify their molecular diagnosis, or documenting population data on genetic variability, disease susceptibility, prognosis, or response to drug treatments.
To build the enterprise, we are engaging the complementary expertise of physicians and researchers, including medical geneticists, genetic counselors, information technologists and bioinformaticians, geneticists, genomic scientists, and statisticians across UF Health, the UF campus, and the state. Our organization is transparent, collaborative, interdisciplinary, and synergistic; with the singular, united goal of transforming medicine with molecular genetic knowledge.
The program is virtual, and building, but engages core partnerships in the UF Health Neurology and Pathology Departments including the Norman Fixel Institute for Neurological Diseases, the McKnight Brain Institute (MBI), the Center for Translational Research in Neurodegenerative Disease (CTRND), and the Pathology Molecular Diagnostic Laboratory. It also engages the Department of Pediatrics, including the Division of Genetics and Metabolism and the Powell Gene Therapy Center. The program also partners with the Department of Health Outcomes and Biomedical Informatics, UF CTSI, and the UF Health Integrated Data Repository (IDR). Dr. Matt Farrer is the current program director. In his academic research, Dr. Farrer oversees the Laboratory of Neurogenetics and Neuroscience (LNN) in the MBI.
Data Generation and Research
Whether offered as part of routine patient care or through a scientific research study, our collective is to build human genetics at the University of Florida. Our partners include the CLIA/CAP accredited UF Health Pathology Labs and the UF Health Integrated Data Repository (IDR), who are working together to implement whole-genome sequencing, data storage, and access, by developing the required facilities, expertise, and bioinformatics pipelines.
Through that partnership, we can now perform CAP/CLIA-accredited genotyping and sequencing, with automated analysis (Illumina Dragen servers Basespace applications including TruSight®) to process raw data [.fq files] to aligned, annotated data [.bam, .vcf] and customized reports. We also partner to provide services for genetic counseling, medical genetics review, and sign out results. With informed consent, subsequent data storage is enabled, with ongoing development for IDR and EPIC integration.
The “GatorGenome” will aggregate data and serve as a UF’s human genetic reference resource to enable population-based analyses, genome interpretation, and clinical trials. We are also working on UF software applications for variant annotation and exploration, to enable retrospective phenotype/genotype correlations and clinical decision support.
Clinical Genetic Innovation and Current Projects
The Clinical Genomics Program promotes the generation of genomic data and its therapeutic translation by helping coordinate access to genomic data across a network of UF clinicians and researchers. High-throughput sequencing and genotyping techniques are universally applied in diagnostic medicine. Genetic results can help identify the most relevant and effective treatment plans, reduce the time it takes to identify appropriate solutions, and ultimately enhance the quality of life of patients. We are working to make all de-identified human genetic data in UF available as an institutional reference for subsequent clinical-genetic discovery. We welcome inquiries from those with patient cohorts that may benefit from medical genetic discovery. Some of our collaborative research projects are described below:
Whole-genome sequencing (WGS) in developmental disorders, intellectual disability & dysmorphism
Comparative genome array hybridization (CGH) is widely used as a first-line test for structural and copy number variants >50kb (SV/CNVs). However, whole-genome sequencing can detect such genomic changes at higher resolution can molecularly resolve precise translocation/inversion breakpoints (SV), copy number variants (CNV), regions of homozygosity (ROH), repeats, small insertion/deletions (in/del), and single nucleotide variants (SNVs). As the cost of sequencing from 5x to 30x depth is marginal once a genomic library is made. Cases that are “negative” for SV/CNVs at 5x depth can reflux to whole-genome sequencing at 30x depth to assess SNVs. We have interpreted the sensitivity and specificity of this approach, at 5x, 10x, 15x and 30x depths, with comparison to prior CGH-array analyses. Whole-genome sequencing can perform genetic analysis at much higher molecular resolution than CGH, with equivalent turn-around-time and for a lower cost.
Rapid WES & whole genome sequencing in the NICU
Neurometabolic disorders are a leading cause of infant mortality in intensive care. Many acutely ill patients are discharged or die before diagnosis and in many cases the cause is genetic. UF NICUs have ~700 premature or ill infants annually. The average stay is 26 days, yet diagnosis and treatment are challenged by an incomplete/atypical clinical picture. By applying ‘rapid’ comprehensive high-throughput whole-genome sequencing as a first-line test, we hope to reduce the disease burden and mortality, and length of stay in this highly vulnerable population. Neonatologists and medical genetic staff working together can judiciously select the most appropriate patients to benefit for an early and precise molecular diagnosis. We have shown that as many as 72% of patients enrolled may receive a genetic diagnosis. Among these, there was an 83% rate of significant and immediate impact on medical decision-making directly related to new knowledge of the diagnosis.
Low-depth whole-genome sequencing
Low-depth whole-genome sequencing for genome-wide association analysis will be used to identify large structural rearrangements (>10kb) but also provides sufficient coverage to enable the reliable imputation of a common framework of >40,000,000 polymorphisms with minor allele frequencies >0.001. Currently, this approach is being used for a research enterprise in brain health versus age-associated neurodegenerative disease. Low-cost custom genotyping (6-45 SNPs/CNVs) for orthogonal validation and polygenic risk score analyses are also available.
Genetic testing in neurologic disorders (WES)
Singleton, trio (proband, father and mother) or family-based exome analysis is now available for neurologic disorders to help solve the diagnostic odyssey experienced by patients with insidious but complex presentations. CLIA/CAP-genetic testing for pharmaco-resistant seizure disorders is being validated for rapid return of results, specifically in pediatric patients. There are currently ~500 genes implicated in epilepsy, with new genes and pathogenic variants identified on a routine basis. The data generated through this clinical service can be used to guide future recommendations for clinical management and treatment of these disorders.
Gene panels and deep sequencing
The UF Health Pathology Labs is currently offering pharmacogenetic testing of genes involved in drug metabolism and deep-sequencing of tumor tissue for major oncogenes for clinical service and research. Tumor samples are sequenced on an Illumina NextSeq (targeting 500x coverage). Sequence data are processed using a customized analysis pipeline that is designed to accurately detect small insertions/deletion and SNVs. Annotated reports are generated for deep sequencing of 177 key cancer genes using proprietary software.
Sequencing UF Health/Shands leadership
In addition to sequencing individuals with a known disease or condition, we are looking to sequence healthy individuals. These may include members of UF leadership to help raise awareness and promote the benefits of genomic sequencing for gene discovery and targeted medicine. Recent studies have shown that 20% of individuals who have their genomes sequenced have medically important findings such as predispositions to arrhythmia, cancer, cystic fibrosis, hemochromatosis, hyperlipidemia, malignant hyperthermia, sickle cell anemia identified, thrombosis, etc.
Polygenic risk scores, genome-wide and phenome-wide association studies
Most common diseases have a genetic component, including atrial fibrillation, coronary artery disease, breast cancer, inflammatory bowel disease, osteoporosis, type 2 diabetes, and vascular dementia. The genetic variability involved has been implicated by meta-analyses of genome-wide association studies. This information, combined with custom genotyping and polygenic risk score analysis, is a simple and expedient method to identify asymptomatic individuals who may benefit from additional screening on a more regular basis, and potentially who may benefit from a pharmaceutical intervention. The same genetic data can be applied to aggregate electronic medical records to identify other diseases, biomarkers, and drug treatments that are correlated, such as the shared genetic relationship between hyperlipidemia and immune diseases. A recent study explores surgery, peri- and post-operative cognitive impairment, and genetic markers related to vascular risk. However, UF Health is working with many exceptional cohorts of patients, and communities, in which similar analyses can lead to quality improvements in care.
Collaborative Research Engagement
The Clinical Genomics Program is currently facilitating a series of strategic planning meetings to convene leadership, identify future research collaborations, and develop shared goals, objectives, and deliverables that focus on the five main pillars of our enterprise: bioinformatics, clinical services, research, laboratory, and educational operations. The Program hosts a series of work-group style meetings where we define the shared deliverables and action plans under each of these research pillars:
We are working with UF IT, bioinformaticians, and data analysts to develop integrated pipelines and platforms for genomic sequencing data management, to permit safe access and storage in a PHI compliant manner. Initiatives include pipelines for whole genome sequencing .fq data alignment and annotation; ClinSeq, a web-browser for genetic variant annotation; long term .fq storage on HiperGator; accessible storage of .vcf data as part of the IDR; and a genetics module for EPIC. First Steering Committee Members include: Dr. Christopher Harle, Dr. Srikar Chamala, Dr. Tanja Magoc; Gigi Lipori, Dr. Erik Deumens, Dr. Jiang Bian; Dr. William Hogan, Dr. Brad Barbazuk, Dr. David Nelson, and Dr. Duane Mitchell.
Initial work started with UF medical geneticists and genetic counselors, to help coordinate and expand their services to deliver individualized patient care while advancing population health-based research. Action items and a white paper have come through the engagement to build UF’s capacity to retain, recruit, and train future leaders, including a new medical genetics residency program. First Steering Committee Members include: Dr. Sonja Rasmussen, Dr. Roberto Zori, Heather Stalker, Jill Hendrickson, Dr. Gustavo Maegawa, Dr. Cheryl Garganta, Dr. Daniel Driscoll, Dr. Barry Byrne, Dr. David Nelson, Dr. Duane Mitchell, and Dr. Michael Okun. Parallel developments are planned with multiple clinical teams.
Our program has focused on the UF Pathology Labs at Rocky Point which already performs CLIA/CAP-accredited genetic testing in clinical service – from human mitochondrial genomes, gene panels for specific disorders, whole-exome, and whole-genome sequencing. In 2020, supported by the Department of Neurology and the Clinical and Translational Science Institute (CTSI), to meet the growing demand for clinical service and research with low pricing, our program acquired an additional Illumina NovoSeq6000 unit for whole-genome and exome sequencing, and an Agena MassArray for low-cost custom genotyping and polygenetic risk score analysis. To unite effort across the UF enterprise there are also partnership discussions with ICBR and commercial providers. Membership of the Steering Committee has yet to be sought and finalized.
At UF, vast quantities of genomic data are being generated that individually and collectively can improve almost every aspect of clinical care by enabling early-stage diagnoses and more personalized health interventions. High-throughput genome sequencing in medicine is undoubtedly a major driver of scientific innovation and is one of the chief distinctions of modernized medical research and a clinical institution like UF Health. Active programs and early adoptees of genomic medicine at UF include neonatology, medical genetics, neurology, pathology, surgery, and population health. Projects are evolving with the Personalized Medicine Program, OneFlorida, and UF Health. Research implementation is translational, to improve care and with a view to developing a sustainable clinical service.
We provide information on the role of genetics and informatics in improving clinical practice and diagnostics, often as a first-tier test. We seek to engage UF Health/Shands physicians, residents, and clinicians to make clinical genomics a part of standard care at UF. Future planning meetings are to include UF leadership, the Clinical and Translational Science Institute (CSTI), the McKnight Brain Institute (MBI), the Center for Translational Research in Neurodegenerative Disease (CTRND), and the College of Medicine (COM). A series of specialty focus groups may evolve, the first of which is a Neurogenetics ‘breakfast club’ to convene expert clinicians and researchers in Neurology, with membership including: Dr. Gustavo Maegawa, Dr. Adolfo Ramirez, Dr. James Wymer, Dr. Katharina Busl, Dr. Tirisham Gyang, Dr. Michael Jaffee, Dr. Giridhar Kalamangalam, and Dr. Parrish Winese
UF Clinical and Translational Science Institute (CTSI)
UF Health Integrated Data Repository (IDR)
UF CTSI Biomedical Informatics (BMI) Program
UF Health Pathology Laboratories
McKnight Brain Institute (MBI)
Norman Fixel Institute at UF
UF Precision Medicine Program
UF Center for Neurodegenerative Disease Resarch (CTRND)
Director | UF Center for Genetic Medicine
Matthew Farrer, PhD
Professor of Neurology (Molecular Neuroscience) | Lauren and Lee Fixel Chair in Parkinson's Disease | Normal Fixel Institute for Genetic Medicine
the clinical genomics program
McKnight Brain Institute (MBI)
PO Box 100236 1149 Newell Drive Gainesville, FL 32610