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NHGRI Unveils Wide-Ranging Recommendations Regarding Sequencing Initiatives

NEW YORK (GenomeWeb News) – The arrival of next generation sequencing power and other new technologies is changing the landscape of genomics research and its applications in medicine and beyond, and the National Human Genome Research Institute is beginning to plot its course to adapt to these changes.

These plans will most certainly involve continued and expanded large scale sequencing efforts, but it also may involve smaller and mid-sized genomic sequencing groups that will take on different types of projects, efforts to increase the availability of samples, expansion of cancer genome sequencing projects, and more human microbiome studies, among others, according to a new NHGRI report.

In "The Future of DNA Sequencing at the National Human Genome Research Institute" report, which was published last week, NHGRI outlines a broad range of recommendations that were developed by a workshop between NHGRI and a number of outside experts that met in March as part of the institutes' long-term planning process. The recommendations target areas including medical sequencing and organismal sequencing, sequencing for human genetics, functional genomics programs, cancer sequencing, evolution, and other initiatives.

The next generation sequencing technologies are resulting in "unprecedented demands" on the ability of scientists to find enough samples for disease and population studies that are covered by proper consent for the work, and the large data sets they generate will place "enormous demands" on informatics infrastructure and data analysis capabilities, NHGRI stated. New technologies also will cause sequencing to become a "significantly more dispersed activity with many research groups other than large sequencing centers able to produce more and more data," the report suggested, which will create new challenges for sample collection, data analysis and deposition, and informatics infrastructure.

In the report, NHGRI said that while the workshop generated a number of good ideas about new projects that could be pursued using new technologies, the institute at this time is not yet prepared to decide which of these will go forward, or how they should be funded. The goal of the workshop was to raise a range of topics and recommendations that NHGRI could use as it drafts its future plans.

The working group proposed a number of broad and specific recommendations, including the following:

• NHGRI will play a role in a filling the need, along with other funding agencies, for more computational biology methods, resources, and infrastructures that will be needed to keep pace with new genomics tools.

• NHGRI's programs also should continue to involve a sequencing program that involves large-scale sequencing centers.

• NHGRI also should encourage the dispersion of genomics tools by encouraging that the tools and knowledge generated in large sequencing centers be made more robust and usable by smaller research labs, and by providing opportunities for smaller, more specialized groups to engage in next-generation sequencing projects that are more appropriate for a small center than a large one.

• NHGRI also will require additional staff resources to administer genome projects that are becoming at once more numerous and more complex.

• NHGRI also should address the technical problem of how to use new technologies to produce "finished" genomes.

• Sample repositories should be created to ensure the continuous availability of high-quality samples.

• Community education projects should be developed, including those covering sample and data quality standards for genome projects, and NHGRI should try to track the large genome projects that are being conducted anywhere in the world.

• In its medical sequencing projects, NHGRI should work with other institutes and centers to identify projects, should increase the diversity and creativity of new projects dedicated to smaller medical sequencing centers, and should ensure that the smaller centers have close ties with larger ones for technology transfer and support.

• Organismal sequencing projects should be planned in order to develop a "package" that would be ready for use by the biological community. These packages would include the reference genome sequence, variation information, some cDNA and RNA information, and automated gene annotation. Draft genome projects of organisms should be upgraded to high-quality assemblies where the scientific need is such.

• Human genetics studies should include development of a catalog of variation to a minor allele frequency of less than one percent to serve as "an enduring resource for human population and disease genetics." There also should be whole-genome sequencing efforts to characterize the sequence variation underlying most common diseases.

• Functional genomics projects should involve implementing deep transcriptome sequencing for genome annotation and functioning, particularly in humans and in important animal models. These programs also should aim to develop single-cell methods to provide improved precision in functional genomics, and new sequencing technologies should be used to perform epigenetic analysis at the genomic scale.

• Cancer genomics programs should include large-scale sequencing using next-generation technologies, and they should involve sequencing the full genomes of all tumors paired with constitutional DNA, include transcriptome and epigenomics analysis using large-scale sequencing approaches in tumor characterization, and they should analyze heritable cancers using the same approach.

• Human microbiome studies should analyze microbiomes of many "more normal" subjects than are now being considered for the Human Microbiome Project, should include the sequencing of host genomes, should analyze the microbiomes of model organisms, and should use sequencing to attain a more fundamental understanding of microbiology.

• Programs focused on genome evolution and model organisms should use comparative analysis to annotate the human genome, should aim to understand the evolution of every basepair in the human (mammalian) lineage, and should attempt to understand the mechanisms and forces, such as adaptation, selection, duplication, etc., and should add value to experimental or disease model systems.

In terms of organization and initiatives, the NHGRI working group also discussed initiatives that would use medium-scale centers to focus on Mendelian diseases; develop technologies and methods to obtain genomic data from single cells or small collections of cells; develop methods to work on "difficult" regions in the genome; use next-generation technologies to develop de novo sequencing and assembly; and a specific initiative to integrate genomics into medicine.

The workshop was part of NHGRI's long-term planning process, which has included the release of several white papers for public comment, other workshops, and forums that will take place over the next year.

More comprehensive coverage of the workshop's recommendations appears in the most recent issue of GenomeWeb Daily News sister publication In Sequence.

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