Integrating Large-Scale Genomic Information into Clinical Practice Workshop Summary (2012) / Chapter Skim
Currently Skimming:
4 The Interpretation of Genomic Data
4 The Interpretation of Genomic Data
Pages 25-38
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 25... ...
• Human genetic diversity and genetic differences between mater nally and paternally derived chromosomes need to be consid ered when interpreting genomic data. The interpretation of genomic data is even more difficult than generating and curating the data, said Muin Khoury of the Centers for Disease Control and Prevention (CDC)
|
From page 26... ...
In addition to clinical utility, a test must have social utility if private and government insurers are to be willing to pay for it. The insurers need to be convinced that a new test, when compared with current standards of care, would lead to improved health by reducing the need for less successful therapy and would decrease costs by preventing more costly outcomes.
|
From page 27... ...
In some cases it already has clear clinical validity and proven clinical and social utility. One well-established application, for example, is human leukocyte antigen typing to prevent idiosyncratic adverse reactions for drugs such as abacavir, an antiviral for treatment of human immunodeficiency virus (HIV)
|
From page 28... ...
It now costs more than $3,000 to have two genes tested, so in the future, sequencing the entire genome could be reasonable by comparison, but, he said, "I don't think we are anywhere near there yet." Discovery of the genetic reasons for undiagnosed hereditary diseases has yielded some remarkable success stories, but in other cases extensive searches have not been successful. It remains to be seen whether the genes that have been uncovered in the recent past, such as those for Miller syndrome (Ng et al., 2010)
|
From page 29... ...
The oncologist and the rest of the clinical care team then can accept the report's simulations or develop their own to administer precision targeted therapy. This is a model in which advances in sequencing, systems biology, and other areas make it possible to reverse engineer disease pathways, to annotate disease networks and drug targets, and to simulate therapeutic interventions with virtual drugs or combinations of virtual drugs.
|
From page 30... ...
30 Primary care Radiologist Surgeon Primary Oncologist Surgeon Patient care Radiologist Administer develops performs presents physician images precision customized biopsy or with orders tumor therapy care plan resection symptoms tests Annotated Reverse Simulate Data Annotated Molecular Pathology disease engineer therapeutic processing treatment diagnostics report networks and disease interven and options (NGS) drug targets pathways tions integration Pathologist interprets results Manual Automated Data output Interactive Trigger Stored data Decision process process and input display action FIGURE 4-1 A model for future cancer care demonstrates how genomic sequencing and network biology will enable personalized medicine.
|
From page 31... ...
The patient's tumor genome was then sequenced along with DNA from his peripheral blood cells. Following genomic analysis, cytotoxic chemotherapy was discontinued, and the patient was started on imatinib, a targeted therapy that disrupts tyrosine kinase signaling, and the tumor responded.
|
From page 32... ...
." Increased integration of genomic medicine in routine care also opens up the potential for increased disparities in health care access and services. Nicholas Schork from the Scripps Translational Science Institute suggested that disparities could well be exacerbated in the short term.
|
From page 33... ...
With the cost of genome sequencing nearing that of routine clinical tests, the implications of such a capability are going to be revolutionary, not evolutionary, Boguski said. "Next-generation sequencing and whole-genome analysis is a disruptive technology." USING A BIOINFORMATICS MODEL FOR INTERPRETATION Individual genomes contain about 4 million variants that are not in reference genomes, with 50,000 to perhaps 150,000 that have not been seen before, Schork said.
|
From page 34... ...
Any novel variants that are identified in functional elements are then considered as potential causative candidates for the idiopathic condition. Annotations and predicted functional effects then can help prioritize variants.
|
From page 35... ...
. Using the bioinformatics tools described earlier, Schork's group found more functional variation in African genomes than in European, Asian, or Native American genomes because of the increased diversity in Africa.
|
From page 36... ...
It will be necessary to integrate information from many parts of the genome using a greater understanding of systems biology in order to derive actionable conclusions, he said. Boguski emphasized the role of empowered patients and participatory medicine in making actionable conclusions.
|
From page 37... ...
Furthermore, this information needs to be in the public domain so that people can use it. How Clinical Trials Will Be Affected by Genomics Each participant in this section also commented on how the realization of genomic medicine will change the role of clinical trials.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.