It’s been an interesting year for the field of genomics as next-gen sequencing technologies continue to emerge, evolve, and in some cases, fade to obscurity. This year also brought some big career and life events for yours truly. Let’s look at some of the highlights.

Common Complex Disease Genomics

In January, I had the thrill of announcing that the McDonnell Genome Institute had won a 4-year, $60 million grant for large-scale sequencing in common complex disease. Helping write that grant (which we actually did in 2015) consumed several months of my life. The previous few funding rounds for large-scale sequencing had essentially been competitive renewals, which were no less onerous to write, but gave existing large-scale centers a home field advantage.

The CCDG program, in contrast, was a new initiative. It also marked a significant shift in the direction of NHGRI’s flagship genomics program to focus only on common complex diseases. Cancer genomics and model organism sequencing were not to be included (according to the RFA), and these happened to be two of our center’s biggest strengths. I honestly feel that we came in with a competitive disadvantage, so winning that $60 million grant was a big deal.

The Opportunity Cost of Factory-Scale Sequencing

Of course, it wasn’t all champagne and roses for us, or for the CCDG program as a whole. Although $15 million per year seems like a lot of money, it was a significant reduction in our operating budget from the large-scale program. That made things tight, which is common in publicly-funded science (and never fun). Also, 80% of the budget goes toward data production, which leaves very little for everything else, such as analysis.

This budget distribution added to a disconcerting trend in public genomics funding in which agencies use large-scale centers to produce data, but balk at providing the funds to analyze those data. As I’ve written before, the vital component known as bioinformatics analysis is not free. In fact, as the cost of sequencing continues to plummet, the cost of analysis and interpretation is rising. 

I hope that in 2017 and beyond, more funding agencies acknowledge the importance of funding data analysis, not just data generation.

Complex Disease Logistics

The four grantees of the CCDG program had proposed a diversity of projects across a rather wide spectrum of complex diseases. Due to the large sample numbers required for statistical power and the limited budget, we couldn’t sequence all of them. Instead, representatives from the CCDG centers and program officers came together to select a few key projects.

Most of the studies that I helped design and propose ended up on the cutting room floor for various reasons (some sensible, others not). For example, age-related macular degeneration — which affects 10 million Americans and helped establish the value of rare variant association studies for common disease — was cut because it’s not fatal.

Then we were off and running for CCDG and another large-scale sequencing effort funded under the Gabriella Miller Kids First (GMKF) program. At least, we wanted to be. The voracious HiSeq X Ten sequencers waited with open maws for DNA samples (and dollars) that were slow to arrive. It turns out that the logistics of getting 20,000 samples from various bio-repositories around the world to a single center were as complex as the diseases we wanted to study.

We had plenty of other samples in-house and ready to go — samples we’d proposed in our CCDG application — but we weren’t “authorized” to sequence them, which was very frustrating. Worse, much of our cancer genomics funding disappeared: NCI took over the Cancer Genome Atlas project and quietly awarded 99% of the sequencing contracts to one institution.

The unfortunate result was wasted time, unused sequencing capacity, and science left on the table. The factory wasn’t running, morale was low, and an even bigger bombshell was about to drop.

The End of an Era

As CCDG finally ramped up in late spring, I learned that my center directors — Rick Wilson and Elaine Mardis — were leaving WashU to establish a new genomics institute at Nationwide Children’s Hospital and The Ohio State University in Columbus, Ohio. It was a wonderful opportunity for them (and a huge win for NCH/OSU) but a time of stress and uncertainty for the McDonnell Genome Institute.

I got a double dose of that, because our fearless leaders asked me to move with them.

It was a big ask. My wife and I both grew up in St. Louis (which counts for something, when you live there) and had put down some serious roots. I’d been at WashU for 13 years. Honestly, I didn’t think I was likely to move. Then I came for a visit to Columbus, and that changed.

The Start of a New Era

I really liked the people I met at NCH, and could see a place for myself in the new institute. There are some outstanding opportunities both for research and clinical genomics. NCH and Columbus are in growth mode, which was a refreshing thing to see. The Midwest lifestyle was very similar to what we had in St. Louis. The work sounded pretty exciting, too: use genomics to help save children’s lives. It was hard to deny the importance of that.

Also, if I’m being honest, I felt like I was in a bit of a rut for the reasons outlined above. The CCDG program is undoubtedly important, and I want to see it succeed, but sequencing 10,000 genomes to find the odds ratio 1.1 variant just didn’t excite me as it did many others. This was disheartening, because I felt somewhat on the fringe of a grant that I’d fought very hard for.

There were other personal and community things going on in St. Louis, too, that contributed to my feeling of malcontent. Starting something entirely new, in a new place, had a certain appeal.

 

In the end, I received two very generous offers: one to stay, and one to go. It was not an easy decision. But I brought my family to Columbus to look around before our summer vacation, and they loved it. That was the tipping point.

Fast forward a couple of crazy months, and we’d left everything (and almost everyone) we knew to start a new adventure in Ohio, with me as a principal investigator (NCH) and assistant professor of pediatrics (OSU). It’s certainly a new milestone for my career, and I’m pretty excited about it.

Old Friends at ASHG

In October, I attended the American Society of Human Genetics meeting in lovely Vancouver, Canada. I had the privilege of moderating a wonderful panel on gene discovery, genetic counseling, and clinical care for inherited retinal diseases. And I was on television! Well, ASHG television, but that counts for something.

I saw a number of old friends and colleagues there, but not nearly everyone I wanted to. The trip went by so quickly. There were (as usual) too many great presentations, but too little time. I will say that the location was easily one of my favorites for this meeting, despite the fact that the American Society of Human Genetics meeting happened in Canada. I’d go there again, which is more than I can say for Baltimore.

Turbulent NGS Technologies

Some fellow NGS bloggers have covered some important developments in the field of next-gen sequencing. Over at CoreGenomics, James has a nice piece on whether or not the world has too many HiSeq X Tens, and points out the fact that sales of the instrument have cooled, and most of the installations are not operating at full capacity.

This is not terribly surprising, given the incredible throughput of that instrument, the minimum buy-in, and the company’s legal restrictions on its applications. There are other factors at play, too: as I’ve mentioned before, in a world with cheap sequencing, samples are the most precious commodity.

Over at Omics! Omics!, there’s a nice piece by Keith Robison on Roche’s breakup with Pac Bio, complete with speculation as to the underlying reasons and a look at the competitive field. Keith is probably my favorite writer in the ever-dwindling genomics blog space. If you aren’t reading his blog, you should.

Wishing for a Productive New Year

Thank you for sticking around MassGenomics through this rocky year. I hope to get back to more routine blog posts in 2017. Until then, happy new year!