Accurate Genome Sequencing

Personalized medicine recognizes that individuals respond differently to medicines and that it can be more effective and safe to tailor the dose or regimen to that individual rather than to a “one dose fits all” approach that has been common medical practice. According to the National Human Genome Research Institute, personalized medicine is “an emerging practice of medicine that uses an individual’s genetic profile to guide decisions made in regard to the prevention, diagnosis, and treatment of disease.” Personalized medicine can also encompass the application of medical imaging and regenerative medicine techniques.

The effective application of personalized medicine is based on the assumption that the genome of the individual is accurately known. In a recent posting, Jason Koeber of Motherboard points out that even the best genome sequencing techniques have an error rate of around 1%. (1)

Two years ago, the National Institute of Standards and Technology (NIST) hosted a consortium to develop genomic reference standards that could be used to evaluate the accuracy of genome sequencing processes. (2)This consortium is called Genome in a Bottle. The reference standards are designed to overcome problems of bias and “blind spots” among sequencing technologies that lead to significant differences in results.

The results of a pilot study were reported in a recent Nature Biotechnology paper. (3)The researchers studied 14 genome and 3 exome data set results obtained from five sequencing platforms to find regions of agreement or disagreement. An arbitration method was used to overcome biases. A reference genomic data set was obtained that can be used with high confidence to evaluate new sequencing methods.

The FDA recently granted marketing approval for the first next-generation genomic synthesizer, Illumina’s MiSeqDx. (4) They have been working with the NIST to develop genomic reference standards.

1. Koeber,Jason “If We Can’t Get Genome Accuracy Right, Personalized Medicine Is a Pipe Dream” March 1, 2014

2. How Well Did You Sequence that Genome?’ NIST, Consortium Partners Have Answer

3. Zook, Justin, et al. “Integrating human sequence data sets provides a resource of benchmark SNP and indel genotype calls.” 32, 246-251 (2014) doi: 10.1038/nbt.2835

4. Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product Development. October 2013.