Last week I attended the clinical genome conference in San Francisco and it was three action-packed days of great talks. The field of clinical genomics is moving fast, with many startups offering clinical sequencing tests as well as medical center research. However, the overall market is stymied by sequestered proprietary databases as well as lack of sufficient database curation, which was a subject that came up in almost every talk. Other key themes were clinical reports (content, delivery, and responsibility) and appropriate upstream processes for sample handling, processing, and data analysis.
Here is an overview of a few of the interesting talks:
Bruce is the Director at University of Alabama where BaseSpace Clarity LIMS is installed in the clinical lab under the direction of Dr. Messian. He discussed three keys areas to consider when integrating sequencing into the clinic:
He highlighted ACMG ACT sheets as being important to follow for newborn screening. He raised a common concern in the field regarding incidental findings (termed the Incidentalome) as scientists are guaranteed to find results that lie outside of the main reason for testing. The outstanding question is what to do with these results as well as how to present them. He ended the talk with a good quote: “The best way to predict the future is to invent it.”
Heidi is the Director of the Laboratory for Molecular Medicine, which is a CLIA lab. We have recently completed a successful BaseSpace Clarity LIMS pilot with the group and they are just sorting out funding after the effects of sequestration. The focus of the lab is clinical myopathy and they started offering targeted sequencing testing in 2011 for $3,200 and now offer whole genome sequencing for $9,000. They always validate their results with Sanger sequencing and this makes up approximately half of the cost of the service. The majority of her talk focused on the challenge of assessing the data, the time that it takes given the annotation databases, and how these data are presented in a clinical report. She did mention GeneInsight at the end of her talk to say that 10 labs are now using it to share clinical knowledge and create clinical reports.
Randy is the founder of InVitae and he gave an inspiring talk focused on the importance of sharing data. The premise of InVitae is multiple tests through whole genome sequencing, all run on Hiseq 2500s. They have an online portal for physicians and patients. He also echoed Heidi and Bruce in saying that the limiting factors in the field are information sharing and assessment of results. He suggested four steps to aggregating clinical data:
He introduced a spin off of Coriell that has partnered with IBM to create Coriell Life Sciences. He discussed their patient portal that allows patients to see and share data with appropriate doctors as well as a way to find doctors for genetic interpretation. He also stressed the importance of identifying allelic diversity and moving from variant centric to haplotype centric to determine diploid status.
His lab is looking at recurring tumors to learn about evolution retrospectively. They discovered gene silencing by methylation of MGMT (a mismatch repair enzyme) and found this caused by a common brain cancer drug (TMZ). They concluded that certain types and doses of chemotherapy can lead to tumor progression by promoting hypermutation (hypermethylation of mismatch repair genes and result is loss of heterozygosity (LOH)) in the primary tumor. Not great news…
Mike had a very interesting talk (as always) that focused on the methylome and the importance of taking this into consideration for genetic testing. His lab has done several methylation studies using Moleculo sequencing technology to obtain longer fragments. They have found that 90% of methylation occurs at the regulatory region of a gene. Their next venture is to determine how methylation patterns differ in different cell types. He also presented results of his own genome and discussed methylation in key genes. He traced the methylation back to his maternal or paternal chromosomes (imprinting) and made the point that it is interesting to see methylation that may have been inherited versus acquired from your environment.
While at the conference, I had the opportunity to talk with a couple of BaseSpace Clarity LIMS customers. One said she loves our software and is so glad to not be tracking work anymore through Excel! The other echoed her sentiment and also called out the implementation and support teams for great support throughout the project and post close.