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Q&A: Max Käller on Serving Sweden's Sequencing Needs through SciLifeLab


Name: Max Käller
Position: Manager of the Genomics Experimental Platform Facility, SciLifeLab, Stockholm, Sweden
Education: PhD, Sweden's Royal Institute of Technology

Sweden's SciLifeLab
, a two-year-old molecular biology collaboration between multiple facilities at four universities in Stockholm and Uppsala, is ramping up its genomic activities thanks to a recent $100 million investment from the Swedish government.

That funding, which follows a $33 million investment earlier this year from the Knut and Alice Wallenberg Foundation, will be used in part to support sequencing activities at SciLifeLab's Genomics Experimental Platform Facility in Stockholm.

Platforms on hand at the facility include five Illumina HiSeq 2000 systems, an Illumina MiSeq, a Life Technologies SOLiD 4 system and a SOLiD 5500 XL system, and two Roche 454 GS FLX+ instruments.

Justin Petrone, editor of In Sequence sister publication BioArray News, spoke to Max Käller, manager of the facility, during a visit to SciLifeLab last month. The following is an edited transcript of the interview.

Can you provide some background on yourself and the facility?

My interest is really in setting up new types of technologies, trying out all of the new cool stuff in the sequencing market, and I am in the excellent position to do that in Sweden, since we have so much funding coming in all the time to buy new stuff. My team is 11 people right now in the lab, and there are about as many people on the bioinformatics side that handle the data. We provide services to the whole of Sweden when it comes to massively parallel sequencing. That is sort of the main focus that we have, and we do some research and development on the side. Joakin Lundeberg, my supervisor, oversees a research group that includes development and research into these types of tools. We have tried to bring in some of the new tools that he sets up and provide it as a service to Swedish academia.

How much demand is there for your expertise in Sweden, outside of SciLifeLab?

We actually went on a Sweden tour yesterday and the day before. We went to Gothenberg, Malmö, and Lund to let people know that we are here to help them with their projects. Otherwise, the majority of projects come from the Karolinska Institute. The smaller universities and smaller cities are just a small part of this. We think they are not really aware that we are here for them. But at Karolinska and other big universities there is a huge demand for our services, a lot higher than what we are able to fulfill. They are sending samples to BGI and all over the place just because we can't keep up with everything that they want us to do. We are talking with some of the professors at Karolinska Hospital about setting up a clinical pipeline which would need as much capacity as we have altogether. So that will probably be starting this fall as a pilot project, and we will see how that takes off.

How much data are you producing?

We are producing about 80 gigabytes per day, and we just scaled up to five HiSeqs from three, so it will increase quite a bit. And we are just bringing in a second Agilent Bravo workstation [for targeted sequencing using the SureSelect protocol] to increase that further, adding new personnel, and other new instruments to see if we can make them available for Swedish academia.

Such as?

We have a nice new Mondrian sample prep system. It uses an electropipetting method to handle samples down to one nanogram, and it moves them around on a small surface of about 1 by 1 millimeter. You can make libraries from very small amounts of DNA. It is for people who can't produce much DNA from precious samples. We just brought in an Argus optical mapper from OpGen to facilitate better scaffolding of de novo genomes. And we have the Bravo. We have set up the Illumina DNA-RNA protocols as well. So we work a lot on automation. I work on it myself and we have been developing quite nice purification protocols for this instrument and for a smaller instrument. We are replacing gel cuts with precipitation beads instead, so it is quite convenient.

How is the bioinformatics side developing?

The bioinformatics team is working a lot on automation of the bioinformatics pipelines, so we are focused on the main applications of sequencing DNA, RNA sequencing, sequence capture, de novo sequencing and resequencing, and we have automated and semi-automated pipelines for doing these things on the bioinformatics side. So we provide these services for free for our users together with the sequencing, and today for standard research this would actually cost more to do than the actual sequencing in a lot of cases. We are trying to provide as much information as possible so that Swedish academia won't have to do this kind of work and specialize in how to perform it. It has been centralized as well.

Data storage must be incredible to support all of that.

We have local storage, which is just temporary. We have been classified [by the Swedish government] as a national resource for sequencing, and they have designated a national resource for data storage in Uppsala, so we are transferring all data to that resource, and that is where our customers can find their data and our analysis. That has been taken care of. It is not just for next-generation sequencing, it is for all types of research data, and it is free of charge for Swedish academics, so it is kind of a neat arrangement. The only problem is that they can't keep up with our increase in production.

You have the five HiSeqs, the SOLiDs, the 454s, the MiSeq. What are you using most, and for what kinds of projects?

We are sort of competing with ourselves within SciLifeLab. Some groups come to us, some groups come to the SOLiD site [at the Uppsala Genome Center], some groups come to the Illumina/454 site at [Uppsala University Hospital], and it is more or less up to the customers. And with [the] grant from the Wallenberg Family Foundation, they have asked us to coordinate all of these entities, so we are currently building a common website where people can enter their projects and request a meeting with any of the sites.

Because the technology is changing so rapidly, how educated are different labs around Sweden about what is available and what can be done with it?

It is very different. We have some people here as research groups that are integrated with our groups. They are very knowledgeable. And there are groups that have a lot of information and know what is coming out, and then the whole scale down to clinicians who are practicing physicians, and they don't know anything about sequencing. They know that it is getting a lot cheaper and that they can get an exome for something like $5,000. We really have a challenge in making the data understandable for them. We are trying to improve the way we relay the data to that kind of group as well. But it's a bit tricky. As a national resource, we are spending a lot of time on trying to figure out which sequencing method and which platform is most suitable for their biological question, so we are trying to set up the sequencing projects as best as we can with state-of-the-art instrumentation. And that is where we see ourselves, as the big contribution to the Swedish research effort. Anyone can send samples to BGI, but it might be trickier for people to get good support and best understand how to do their experiments.

How would you compare Swedish genomics infrastructure to what is available in Germany or the UK or China? Do you feel that you are ahead of the pack, or that you are trying to keep up with what is being made available to researchers?

I think we are quite on top of things, and we are driving research and development in the field. And we are on top of the developments internationally when it comes to sequencing methods and instruments and so on. I think that Sweden is a bit ahead in Europe when it comes to biotech in general and sequencing in particular. That said, I think there is a lot more room for these kinds of activities in Sweden. I think there is a lot more stuff to sequence that people would like to sequence and that they haven't yet realized they should sequence. Eventually, this is going to the clinics in Sweden, and this will happen really soon.

What is the clinical impact of having all of these platforms available here? I understand that a new hospital is going to be located right around the corner.

We'll see who will lead that, but I think SciLifeLab will be part of the actual routine clinical work in sequencing, either driven by SciLifeLab directly or as a site for exchanging knowledge and [introducing] new protocols. And a lot of our customers who are here are professors at Karolinska Institute with their clinics at the Karolinska Hospital and they are pushing us quite hard actually to increase our capacity to sequence all of the patients that they want to sequence. So, it is quite fun. The Swedish healthcare system is changing right at this moment in this building, more or less.

Do you see still demand for expression microarrays?

I think expression arrays is more or less a dying field. People want to keep using what they are used to. We tried, with our bioinformatics pipeline, to make the data interpretable just like microarray experiments, so they don't really have to bother with bioinformatics even if they switch.

The Swedish government recently announced that it will commit $320 million to life sciences, $100 million directly for SciLifeLab, over the next four years. So where will this lab be in 2016?

In 2016, we will have just as big a site as this one doing only clinical sequencing. And we are in the process of starting this work already.