A decade or so ago, the phrase ‘translational research’ began making its rounds through laboratories- it was supposed to take molecular biology results and apply them directly to patients. It brought about things like gene therapy, stem cell therapy, and so forth. You get the idea- valuable research, but not immediately injectable.
Valuable and cheap
However, amongst other things, translational research may have influenced next-generation sequencing, at least in its ability to find mutations, SNPs and other genetic incidents which may underlie disease. Next generation sequencing is now cheap enough, and valuable enough, to start playing roles in clinical trials.
Discovering new disease categories
Taking the ‘translational’ part literally, NGS can take genomic information and translate it into disease-specific information at the clinical level. At the non-profit Rare Genomics Institute (RGI) for example, patients with rare (and possibly inherited) diseases submit samples to academic labs (Washington University St. Louis, Johns Hopkins University, and Yale are partners) for rapid whole-exome sequencing and interpretation by genomics researchers. Sometimes, a new SNP or mutation is found- in a few cases a new disease category is discovered.
Turning the clinical trial on its head
NGS is now a growing part of clinical research. Organizations such as the RGI can use NGS to turn the clinical trial process on its head. Instead of a hypothesis-driven clinical study, they’re hoping that enough patients come to them to form a hypothesis. According to the site Clinicaltrials.gov, the number of studies that include ‘genomic sequencing’ in their protocols rose from 35 in 2011 to 58 in September 2012. They include:
– A study using data from the newly sequenced ‘microbiome’ is comparing sequences from bacteria in the bladder to test the effectiveness of an experimental drug from Astellas Pharmaceuticals against overactive bladder.
– Eric Topol (a Scripps Research Institute cardiologist and pioneer in the application of sequencing and other technologies) is leading an effort to collect genomes of people with undiagnosed disorders to determine the existence of rare diseases (a kind of more traditional method which the RGI is tackling).
– An ambitious study at the University of Toronto, Ontario is using genome-wide sequencing to determine all the mutations that exist in people who have cancer (solid tumors, at least).
The known knowns and the unknown unknowns!
The studies above illustrate a number of changes happening in the match of sequencing and clinical trials. First, the focus on exome-only sequencing is expanding to include whole-genome screening, no doubt because genome-wide association studies (GWAS) can find ‘unknown unknowns’ as well as ‘known knowns’,and GWAS sequencing is now faster and cheaper. Second, large-scale epidemiological/sequencing studies can provide a trove of genetic and disease information, including possible new biomarkers. Such studies include the recent ENCODE database, and a 3,000-patient study by the National Cancer Institute on gene expression in lymphoma, leukemia and multiple myeloma.
So, when the auditors of human subjects come into your lab and start asking questions, you’ll know that nothing was lost in translation!