One of the popular questions on the program this past year is how those doing sequencing decide between the quality of Pacific Bioscience's long reads and the cheaper short read technology, such as that of Illumina or Thermo Fisher. Today’s guest provides the most clear and dramatic answer yet: use the PacBio system exclusively.
We heard this from Steve Marsh, the Director of Bioinformatics at the Anthony Nolan Research Institute in London. Established in 1974 by the mother of a boy with a rare blood disease, the Anthony Nolan Institute is a world leader in blood crossmatching and donor/patient registries. Steve and his team at the Institute have dramatically improved the resolution of HLA typing, one of the methods for matching a donor’s blood tissue with that of the transplant recipient.
Thirty years ago when Steve entered the field, HLA typing was performed with serology and there were just 119 HLA antigens that were known. “We thought 119 was a lot of diversity,” says Steve. With the advent of genomic tools in the 90’s, HLA typing moved to the level of the genetic allele, done first with PCR and then with sequencing. “We knew that the HLA molecules were polymorphic, but now we know they are hyper-polymorphic. . . For example, 'A2' is a specificity, and serologically we recognized the specificity 'A2,' and that was it. We now recognize that there are over 500 different variants of A2,” Steve explains.
Knowing more about the incredible diversity of blood types can make achieving a donor/patient match seem all the more prohibitive. More variables mean fewer candidates. But research at the Anthony Nolan is now paying off and is robust enough to make a difference in the clinic. Ideally blood registries will provide precise matches and do so immediately.
All this explains why Steve is so keen on the PacBio system. In a field where the quality of the sequencing makes the difference between the right match and not, the increased price of the longer reads is worth it.
Finally, it should be said that we recorded this interview with Steve just before PacBio announced their new higher throughput Sequel Sequencer. This new smaller footprint instrument is promised out in 2016 at half the price, seven times the throughput and with the same high quality long reads. The decision between quality and price in the world of sequencing will soon be easier.