The mission of the Partners HealthCare Center for Personalized Genetic Medicine is to utilize genetics and genomics to improve the care of patients through the promotion and implementation of personalized medicine in caring for patients throughout the Partners HealthCare System and in healthcare nationally and globally.
In the past several years there has been a revolution in human genetics that is having a very significant impact on virtually all specialties of medicine. Several scientific advances are responsible for this revolution. One of them is the recognition and validation that the genetic composition of individual humans has a significant role to play in an individual’s health and predisposition to common diseases such as heart disease and cancer. A second scientific advance is the availability of the human genome sequence and the many high throughput technologies developed and advanced during and since the Human Genome Project. A third is the imminent ability to completely sequence the human genome in real time at very low cost.
This new genomic era provides excellent opportunities to identify gene polymorphisms, genetic changes that are responsible for human disease, and to build an understanding of how such changes cause disease. In the clinical arena, it is now possible to utilize the emerging genetic and genomic knowledge to diagnose and treat patients. It is anticipated that such knowledge will revolutionize medical practice result in an advance in personalized medicine. The knowledge of the genetic basis of human disease is ushering a new era in drug development that is focused on targeted drug development. Genetic profiling of Partners HealthCare patients will help in defining individuals risk for clinical outcomes and their response to specific drugs.
Harvard Medical School (HMS) and Partners HealthCare System (PHS) established the Harvard-Partners Center for Genetics and Genomics (HPCGG) in 2001. The Center was launched in recognition of the excitement of the Human Genome Project and as an early commitment to the importance that genetic and genomic knowledge would play in human health. HPCGG offered a framework for aiding genetic discovery, stimulating research that would lead to the integration of genetic knowledge into patient care, developing an information infrastructure that would facilitate the application of genetic and genomic data in research and clinical settings, applying genetic discoveries and technological advances in the development of molecular diagnostic tests that could be used in everyday medical practice, and building an education program that would expand the number of clinicians and investigators trained in genetics and genomics.
In late 2008 the name of the Center was changed to its current one to reflect a heightened focus on translational issues related to moving genetics and genomics into clinical practice. Previous direct discovery components were moved out of the Center and into affiliated academic medical centers. The name change also affirms Partners HealthCare’s emphasis on personalized medicine.
What is Personalized Medicine?
Personalized medicine is the ability to determine an individual’s unique molecular characteristics and to use those genetic distinctions to diagnose more finely an individual’s disease, select treatments that increase the chances of a successful outcome and reduce possible adverse reactions. Personalized medicine also is the ability to predict an individual’s susceptibility to diseases and thus to try to shape steps that may help avoid or reduce the extent to which an individual will experience a disease.
For personalized medicine to be a fully functioning reality at the clinical level, certain features are essential: an electronic medical record, personalized genomic data available for clinical use, physician access to electronic decision support tools, a personalized health plan, personalized treatments, and personal clinical information available for research use. Partners HealthCare has made a firm commitment to the principles of personalized medicine and to the importance of genetics and genomics in delivering the best care of patients. To that end PHS also has committed to ensuring that the features above are or will be available.
PCPGM’s strategic approaches
The essential feature of the revolution in genetics and genomics has been an explosion in the amount of data available for use in translational research. Whole genome interrogation is now commonplace and it is not uncommon to see integration of transcriptomic and genomic data at the genome level in clinical studies. This massive data profusion has enhanced our ability to predict clinical phenotypes and to predict clinical outcomes on the basis of genome scale data. However, to be able to do this sort of prediction investigators need several tools. First, they need a robust bioinformatics infrastructure with secure pipelines and robust algorithms for data cleaning and manipulation. Second, they need very strong bioinformatics platforms for data analysis and data management. Third, they need access to large numbers of very well phenotyped patients. Finally, they need access to the genomic platforms to create genomic scale data on these patients for prediction of clinical outcomes. PCPGM makes all of these resources available to Partners investigators through a highly developed infrastructure of five basic units:
- Bioinformatics and Genetic Statistics
PCPGM serves all Partners investigators who desire to do projects involving core laboratory support or the development of Partners Research Patient Data Registry (RPDR)-based data marts for research use. The Center is expanding its IT infrastructure to support these projects. This development is being implemented by Partners Research IT and involves bringing together several Partners genetics programs, including Genetics Enter Medicine (GEM), Personalized Medicine Biorepository (previously known as BETR), Informatics for Integrating Biology & the Bedside (i2b2), RPDR, Crimson, and PCPGM.
- Infrastructure for Partners Researchers
PCPGM has built an infrastructure that will ensure leadership in the areas of genetics and genomics research, as well as the clinical application of new discoveries. It consists of:
Biosample Repository — This core laboratory has automated platforms for making DNA from whole blood, freezers for storing samples and the capacity to make immortalized cell lines.
Sequencing Core Laboratory — The Sequencing Core has the ability to provide sequencing support for conventional dideoxy sequencing as well as next gen sequencing methods using Illumina Solexa technology. The core has over 40 active customers from MGH and BWH.
Genotyping Core Laboratory — This facility provides high-throughput methods for microsatellite and single nucleotide polymorphism (SNP) based genotyping of human and mouse populations utilizing many different platforms. The facility acts as an important resource for investigators who are interested in using large-scale genomic methods for disease gene discovery. There are currently over 45 customers from MGH, BWH and HSPH.
GeneChip® and Microarray Core Laboratory — The microarray facility provides expression-profiling technologies, as well as informatics tools and expertise for analysis and interpretation of the profiling data, for all members of the HMS and PHS community. The Center will support, extend and help modernize several existing gene chip facilities . The Center will provide commercial as well as high quality “home-made” gene arrays at affordable prices to all members of the community. It currently makes available human, mouse and Drosophila arrays. The Center’s facilities, in conjunction with existing facilities, also provides hybridization, washing and data acquisition services on a fee-for-service basis. There are currently over 40 customers from MGH and BWH.
- Laboratory for Molecular Medicine
An important goal of the Partners HealthCare Center for Personalized Genetic Medicine is to translate the knowledge gained from genetics and genomics to more accurately diagnose and treat the large patient populations served by the Partners affiliated hospitals. Already several hundred genetic and genomic tests are available, and it is expected that several thousand additional tests will become available in the next few years. These tests are expected to help in diagnosis and prognosis and also in determining the appropriate drugs for individual patients. The Laboratory for Molecular Medicine (LMM) is a CLIA- and state-approved laboratory that provides genetic and genomic testing for patients around the world. It is also a leader in the development of new approaches to genetic testing and the integration of genetic testing into health care.
- Genetics Enters Medicine
Using the i2b2 methodology the Center is developing the ability to provide data marts of Partners patients with anonymized phenotype and blood samples to be made available for specific projects. Currently this is still in the pilot phase and is not available to all Partners investigators. Pilot projects have been done in asthma, rheumatoid arthritis, major depression, hypertension, obesity and diabetes mellitus.
The rapid pace of advancement of knowledge in genetics and genomics poses a major educational challenge for all health providers, investigators, and the public. PCPGM plays a leadership role in providing education on the importance of genetics in human health and disease and the ethical, legal and social implications of this knowledge. Teaching programs include education for postdoctoral trainees in genetics, practicing physicians, and other health professionals.