NEW YORK (GenomeWeb News) – The National Human Genome Research Institute today unveiled an updated model of its flagship genome sequencing program that represents a partial shift away from large-scale sequencing and toward applied genomics and informatics projects.
The new $416 million, four-year plan, now known as the Genome Sequencing Program, will use roughly the same resources as its predecessor, the Large Scale Sequencing Program, but a portion of these funds will support new programs aimed at shifting basic genomic science into clinical genomic medicine, NHGRI leaders said during a conference call today.
The revamped program will still fund its three Large Scale Genome Sequencing Centers, providing $86 million per year, with The Broad Institute receiving $35.9 million per year, The Genome Institute at Washington University in St. Louis receiving $28.4 million per year, and the Human Genome Sequencing Center at Baylor College of Medicine receiving $21.3 million per year.
A new effort to use sequencing to study rare diseases caused by single gene mutations such as cystic fibrosis, called the Mendelian Disorders Genome Centers Program, will receive $48 million over four years. Supported in part through a partnership with the National Heart, Lung, and Blood Institute, this program will provide $5.2 million per year to the Center for Mendelian Genomics at the University of Washington; $2.8 million per year to the Center for Mendelian Disorders at Yale University; and $4 million per year to a new joint effort between Baylor College of Medicine and Johns Hopkins University called the Baylor-Johns Hopkins Center for Mendelian Genetics.
NHGRI also aims to fund research into ways for doctors to use sequencing information in the clinical setting, so it is providing $10 million per year over four years to fund the new Clinical Sequencing Exploratory Research Projects grants program.
These new grants will provide $1.8 million per year to Baylor College of Medicine; $2.4 million per year to Brigham and Women's Hospital; $2.2 million per year to Children's Hospital of Philadelphia; $1.6 million per year to the University of North Carolina at Chapel Hill; and $2.3 million per year to the University of Washington.
Yet another new program will focus on meeting the need to create new software programs that investigators can use to analyze massive volumes of genome sequencing data.
The Informatics Tools for High-Throughput Sequence Data Analysis program will provide $5 million per year for four years for projects that will further develop existing software to make it more accessible and to speed up analysis projects. These grants, which will be awarded early in 2012, will use various funding mechanisms including cooperative agreements and Small Business Innovation Research grants.
NHGRI gave notice that it planned to shift the old large-scale sequencing program toward applied projects and informatics earlier this year, when the institute made public an outline of the rough vision for the projects it announced today.
"That vision builds on the success of the Human Genome Project and genomic studies that have been pursued since its completion, and then charts a course to accelerate the application of genomics to medical care. With the investments made over the last decade, and the new ones that we are now announcing, a path towards the realization of genomic medicine can be envisioned," NHGRI Director Eric Green said in a statement today.
This new round of funding for the Large-Scale Genome Sequencing Centers will continue to support ongoing basic research projects into the genetics of common diseases and projects such as the Cancer Genome Atlas. They also will engage in new medical initiatives to develop technological advances in sequencing and information management systems and software development.
"The new grant allows us to build on our earlier work and more effectively decode the information contained in our genomes to better understand, diagnose, and cure disease," Richard Wilson, a professor of genetics and director of Washington University's Genome Institute, said in a statement. "In this next phase of funding, we will discover new sequence variants that can be used to select the best treatment options for patients – a primary goal of personalized medicine."
The three Mendelian disorders centers will collaborate with a network of rare disease experts to gather samples and sequence genomes to identify variants for disorders.
"We expect that the knowledge about genetic variants that underlie Mendelian disorders will facilitate rapid and accurate diagnosis and might lead to new therapeutic approaches," Lu Wang, NHGRI program director for the Mendelian Disorders Genome Centers Program, said in a statement. "This knowledge can also shed light on more common, complex diseases that involve similar genes, pathways, and phenotypes, and contribute to the understanding of basic human genetics."
These centers already have solicited the samples from researchers studying several hundred disorders, all of which will be coordinated by the University of Washington. These centers also plan to join the International Rare Disease Research Consortium, which aims to develop diagnoses for most rare diseases and treatments for about 200 disorders by 2020.
The five Clinical Sequencing Exploratory Research Projects will study ways that healthcare professionals can use genome sequencing information in the clinic and will include input from physicians, ethicists, scientists, patients, and families. The grant winners also will form a consortium to look into the ethical, legal, social, and psychological issues that may spring from the arrival of genomic medicine in the clinic, such as genomic data sharing and interpretation. That group also will focus on finding ways to help physicians and genetic counselors interpret data for families and patients.
"At NHGRI, we foresee genome sequencing becoming a routine part of medical care. We regularly hear anecdotal accounts of people who have made remarkable recoveries from illness by early applications of genomic medicine, especially for some types of cancer and acute diseases," said Brad Ozenberger, NHGRI's program director for Genomic Medicine, who is overseeing the new clinical sequencing initiative along with Jean McEwen, program director for the Ethical, Legal, and Social Implications Program. "These projects are exploring the best ways to widen the use of genomic medicine in a responsible, respectful way."
The Children's Hospital of Philadelphia will use its funding to pursue three clinical sequencing projects. One of these projects will enroll four cohorts of children in certain disease groups, including sudden cardiac arrest and intellectual disability, among others.
"Each of these groups of disorders cannot be easily diagnosed with a gene-by-gene approach, so experts from several disciplines will develop tools for sequencing the patients' whole genomes and then interpreting the vast amounts of data," explained CHOP clinical geneticist Ian Krantz, a co-leader of the project. "Not all the gene mutations we find will be clinically useful, and we will work with families to understand what information they desire, and how clinicians should present it."
The other CHOP projects will include one that will build a framework for systematically assessing gene sequence data, integrating it with clinical and diagnostic observations and developing tools for delivering information directly into patients' electronic health records, and another that will study the impact and outcomes of genetic testing in children.