For the last 6 months we have been working with Genomics PLC to help design and prototype a new product. Genomics PLC are a very talented team in Oxford who are building applications that uncover links between genetic variation and human disease.

It has been fascinating to further develop our interest in genomics and its relationship to real-world healthcare. Although we aren’t able to speak about the details, we can say that we have learnt a lot about the potential for software to help make sense of genetic data.

From a methodological point of view, we are always striving for fruitful collaborations between the disciplines. Working with Genomics PLC provided a fantastic opportunity to get scientists, software engineers and designers working together in a productive and satisfying way.

So why is a designer interested in learning about bioinformatics?

I’ve been asked this question many times during my stay at the Wellcome Trust Genome Campus in Hinxton, where I attended the EBI Bioinformatics Summer School two weeks ago.

At Science Practice we often work with bioinformaticians helping them build expert tools. Not long ago we collaborated with the Goldman Group at the EBI and developed Sequence Bundles. Most recently we have been testing the MinION, sequencing soil metagenomes, and working with biomedical startups and companies as part of Ctrl Group. Each project requires us to sit down for a few hours or days and learn the science behind it. This learning curve is something I personally really enjoy. And because every single project we work on at Science Practice is very different from another, there is always a lot of diverse learning going on.

So my answer to the question I was asked was:

Because I’ve got a general second-hand understanding of bioinformatics, but no direct hands-on experience of how it’s done.

And we want that first-hand “done-it-myself” experience. This keeps us very close to what actually happens in the lab, in the clinic, in the field — in the very places where this insider expertise matters. That’s why I decided to spend a week in Hinxton together with 30 researchers, postdocs, and PhD candidates from around Europe to learn the science of bioinformatics in practice.

Hinxton Hall at the Wellcome Genome Campus

The course took place at the Wellcome Genome Campus which was one of the key centres involved in the seminal Human Genome Project. One of the institutes based at the Campus is EMBL European Bioinformatics Institute — the organiser of the Bioinformatics Summer School — and one of the world’s main centres for storing, curating and providing biological sequence data. The campus itself is set in rural England in vicinity of the old Hinxton Hall.

The course had a balanced mix of theory and practice. On day one Bill Pearson from the University of Virginia kicked off with a general primer in bioinformatics as an experimental science: How do we get answers to the questions that we want answered? Which questions cannot be answered by bioinformatics at all and which ones cannot be answered just yet? What are the positive and negative controls in bioinformatics? Why do we search for similarity and what are the statistics of excess similarity? And why statistically significant structure similarity can be present even in absence of statistically significant sequence similarity?

This was followed by several short tutorials on using bioinformatics resources offered by the EBI, including using the Ensembl genome browser, querying nucleotide and protein databases online, and also requesting jobs programmatically via the command line.

All that theory was an indispensable primer for launching the main activity of the Summer School on day two — a practical bioinformatics project. There were four project teams to select from:

• Genome Assembly and Annotation
• Phylogenetics
• RNA-Seq and Networks
• Structural Biology and Functional Prediction

I chose to do the Genome Assembly and Annotation project, as it had most to do with clinical genomics and genomic medicine which is in one of our areas of interest at Science Practice.

Visual notes from the bioinformatics lab

The canvas for the bioinformatics exercise was the 2011 E coli outbreak in Germany and France. The outbreak was caused by the highly pathogenic Shiga toxin-producing O104:H4 strain of Escherichia coli. Infected patients were at risk of suffering from bloody diarrhea (around 4,000 cases) which could progress to life-threatening hemolytic uremic syndrome, known as HUS (859 cases). 50 patients with severe cases of HUS died. The 2011 E coli outbreak was unusual for the rapid response in which multiplatform sequencing was brought to understand the epidemic, which is outlined in this PNAS paper.

Our task was to re-trace the investigation done during the outbreak. Working in a group of four (myself, Tracy Munthali Lunde, Massimiliano Volpe, and Dag Harald Skutlaberg) we followed these steps:

1. Obtain raw genomes from the outbreak strain sequencing experiments from the European Nucleotide Archive (data quality checked in FastQC);

2. Assemble genomes using the BWA mapping assembler — we worked with strains 11-3677, 11-4623, and 11-4632 described in the PNAS paper, and the E. coli TY-2482 reference obtained from the GigaDB database;

3. Convert, sort, index — use samtools to convert and sort assembled SAM files into an indexed binary BAM file that can be displayed in the IGV genome browser, and which can later be used for calling variants;

4. Call variants between the TY-2482 reference sequence and the assembled genomes 11-3677, 11-4623, and 11-4632 using freebayes;

5. Annotate genome using Prokka to identify which regions of the reference sequence are protein coding — this will help to understand which variants are important;

Gene number 03634 in IGV browser, screenshot by Massimiliano Volpe

We ended our project with a little investigation into the variants identified in the assembled genomes. For example we found out that about 60% of all variants in all three genomes fell within the annotated genes.

As a side project, we also managed to compare the performance of three de novo assemblers: Velvet, Abyss, and Spades. With the genome data we used, the comparison was won by Spades.

In the end, our process involved running the sequence data through a series of tools operated from the UNIX command line. Even though very simple, lacking any investigation into detailed algorithm settings and tested only on three datasets; by the end of the EBI Summer School we have succeeded to prototype our first bioinformatics pipeline.

Producing one's first ever VCF file feels great! 543 variants in a 5mbp E. coli genome. Highly toxic serotype! pic.twitter.com/dBsDNELuHQ

— Science Practice (@sciencepractice) June 15, 2016

The EBI Bioinformatics Summer School was a fantastic learning experience that will help us do even more in the prospective bioinformatics and genomics projects at Science Practice. For those interested in trying out some bioinformatics on their own, here are the Lab Notes (shared under CC-BY-4.0) that I prepared during the course. Happy assembling!

We’re looking for someone passionate about science, tech and innovation to join our team over the summer!

• Location: 83-85 Paul Street, London EC2A 4NQ, UK
• Term: 3 months
• Hours: Full-time
• Starting date: June 2016
• Salary: The internship will be paid, the rate will be negotiated with the successful applicant based on experience.

Things have been pretty lively in the studio lately and we’re looking for another pair of hands to help out with some of the research work!

By means of introduction - we’re Science Practice, a design and research company based in London. We work across a variety of areas and collaborate with scientists to help put their research into practice. Whether we’re designing challenge prizes or humanitarian ones, trying to sequence a virus without a lab or creating new methods for visualising genetic data, we’re always looking at ways to integrate design principles with the processes and methodologies of science.

The role

We’re looking to recruit a recent graduate to support our work on researching and designing challenge prizes. The role will involve:

• Supporting the team research technological innovations and their impact on addressing social problems;
• Writing key research findings and helping prepare external project documentation;
• Supporting expert engagement work - including logistical tasks such as identifying key experts in a specific field and arranging interviews with them, as well as taking part in the interviews and synthesising the main ideas;
• Working closely with a team of international partners in designing the structure of several challenge prizes;
• Completing important and often time sensitive ad hoc project tasks.

Our intern

• Passionate about technology and its potential for social impact;
• Interested in innovation and tools for supporting innovation such as challenge prizes or competitions;
• Strong academic credentials - recent graduate of a Bachelors or Masters (preferably in an engineering or technology related degree), with a First or 2.1;
• Strong research skills - ability to understand and synthesise complex information quickly;
• Excellent written and verbal communication skills;
• Highly organised, with a close attention to detail and high standards of accuracy;
• Efficient, self-motivated and able to manage priorities to meet deadlines;
• Able to work on location in London, UK.

If you’re keen and ready to give a helping hand, please send an email with your CV and a brief cover letter to Ana at af@science-practice.com. Thanks and looking forward to hearing from you soon!

The potential for Oxford Nanopore’s MinION to revolutionise genomics has been well documented, and for good reason. As we and others have mentioned before, they have drastically reduced the size of sequencers so that their device will fit in a pocket. Perhaps as importantly, the protocol to prepare samples for sequencing is significantly simpler than traditional sequencing, raising the possibility of this technology being used by more and more people interested in genetics - including us!

Our MinION running

Having recently conducted a burn-in experiment to check that our MinION works and to familiarise ourselves with the protocol, we had been racking our brains for a good experiment to use our remaining 2 flow cells for.

Sequencing for soil health

As one of our current focuses is soil health we thought it would be interesting to investigate whether we could extract DNA from the organisms found in two different soil samples, sequence them using MinION, and use the species identified to infer information about the soil properties. After some further digging on Google we were unable to find evidence of anyone else who had tried this, giving us even more reason to give it a go!

The analysis we were intending to do was made possible thanks to an app for Metrichor (Oxford Nanopore’s analysis software) called What’s In My Pot (WIMP). WIMP connects to the NCBI database of bacterial, fungal and viral genomes and matches reads sequenced by MinION to their respective species.

Mile End Park and a Bloomsbury vegetable patch were our chosen places to take soil samples

Our first steps were to identify two places to collect soil samples from, and to find a way to extract DNA from the bacteria and fungi found within them (known as the metagenome). For the soil we settled on two samples from London: one from a worn patch of ground in Mile End Park, and one from a shared vegetable patch. Our hypothesis was that there may be detectable differences between the cultivated and non-cultivated soils.

Extracting DNA from soil

DNA extraction was easier than you may expect. We were able to order a DNA extraction kit from MO BIO called Powersoil which was simple to use and took about two hours to go from sample to DNA in a lab at Imperial College London. Ordinarily a biomedical lab, we raised a few eyebrows with our soil experiments!

Our soil samples ready for DNA extraction

The next step was to find somewhere to prepare the DNA and to run the MinION sequencing. As we were well aware from our burn-in experiment, there are a number of pieces of lab equipment that are necessary that we do not have access to, and so we needed to find someone with lab space who would be willing to work with us on this mini-project.

Visiting York

Through twitter we managed to find James Chong at The University of York, who had recently given a talk on using MinION to sequence bacterial 16s ribosomal RNA, and asked if he might be interested. Thankfully for us, James was incredibly generous with his time and knowledge, introduced us to his equally helpful post-doc Anna Alessi who had been using MinION, and offered to have us visit his lab and run the experiment.

Excited to be in @insanity_one lab today @yorkuniversity! sequencing soil creatures with the #minion @nanopore pic.twitter.com/3KbyjYRoVR

— Science Practice (@sciencepractice) 5 May 2016

When we arrived in York we were warmly welcomed by James, Anna and Farah Shahi who is a medical doctor at the start of a research project using MinION and is learning lab techniques. After picking James’s brain for advice for our soil health projects we quickly got going on the MinION protocol, starting by checking whether we had enough DNA using Qubit, a fluorometer.

We were relieved to find that we had more than enough DNA, and so proceeded with the same protocol as we did for the burn-in, only this time we prepared two samples in parallel: the sample from the park and the vegetable patch. By the end of the protocol we were pleased to have two good DNA libraries that met Oxford Nanopore’s suggested quantity requirements.

Relieved to find that we extracted enough #DNA from soil to sequence on the @nanopore #minion today #dnaparty pic.twitter.com/ZnMWaqXI0G

— Science Practice (@sciencepractice) 5 May 2016

While the wet-lab component of the day went without problem, we did have some issues with running MinION itself. Firstly we were unable to get our laptop to recognise the MinION. We were aware that this could be temperamental from our experiences in the burn-in, however for this experiment it simply did not manage to acknowledge the device. Fortunately for us, James has five MinIONs permanently connected to five laptops and so we were able to use his.

Using DNA binding magnetic beads and a magnetic tube rack to isolate our DNA samples

Silent flow cells

Having decided to use James’s MinION we then tested out our two flow cells. Although we had stored them how MinION recommended, and both were visually in good condition, the test run indicated that we had 0 working pores on either flow cell. Despite consulting Anna, a bioinformatician and even the Head of Genomics, we were not able to get to the bottom of this. We suspect there was a serious underlying problem with these flow cells, rather than a degradation of pores.

A MinION flowcell, the bubbles that are visible can hinder the experiment

Fortunately Anna and James came to the rescue again, and allowed us to use two of their spare flow cells. Although they were not in excellent condition (there were visible bubbles covering the pores), and only had around 150-400 active pores, after getting this far with our experiment it would have been a shame not to finish.

At work in the lab setting up our MinION runs

We ran the MinION overnight, and in the morning, reloaded with more of the libraries we had prepared and ran again (this is a trick that James and Anna have found improves the number of usable reads). As expected the data we got was relatively poor quality, with the majority of reads not meeting Metrichor’s quality control.

Genetic sequencer may be pocket-sized but we have the entire teaching lab to ourselves to run it @nanopore #minion pic.twitter.com/q0oQEAlb4u

— Science Practice (@sciencepractice) 6 May 2016

What’s in my pot?

Despite having few good quality reads we decided to run WIMP for both samples, to see what it was able to identify in each sample, and to get a better idea of how the app works. Although we can’t draw any confident conclusions from what we found, there were some small hints that it would be possible to use MinION combined with WIMP to gather useful information about soil.

For example several bacteria capable of metabolising common environmental pollutants were identified in the sample of soil from the park (Nocardioides, V. paradoxus), while the soil from the vegetable patch, which has had manure and compost added to it, had bacteria often found in sewer sludge and wet soil (Thauera). Both samples had many different bacteria involved in the nitrogen cycle.

What's in my pot showing some of the species identified in the park sample (left) and the vegetable patch sample (right)

Cautious optimism

It is important not to over-analyse what we saw - the low read count meant that anything we didn’t see is as likely to have not been sequenced as absent in the sample, and anything we did see could easily be misinterpreted by the software as the wrong species. Also these were the results of just two samples. The entire experiment would need to be replicated in order to begin to make any kind of solid conclusions about inferring soil properties from their metagenomes using this method.

Watching our data come in on the MinION desktop software MinKNOW

Nevertheless the experiment can give broad encouragement that it should be possible to gain a rich understanding of a soil metagenome, and from this information infer properties of soil health and environment using MinION and WIMP. A distinct advantage of using MinION is that, with good quality data, you can make estimates about the proportions of different species in a sample, as this is related to the number of reads for each species.

Although there are still many technical challenges with using MinION, with lab space, some patience and guidance from someone with experience, it is a technology with remarkable potential. While it would take a lot of effort and significantly better microbial knowledge than we currently possess, the possibility of using nanopore sequencing to gain a better understanding of soil health is genuinely exciting.

If you are interested in discussing this project, our results or having a look at the data we collected, please get in touch!

What are we trying to get them to do with this activity? Will it take too long? What if we work backwards from the application form? What is the main message of the day? How can we encourage iterative thinking?… We need how many post-its?!

We had a lot of questions.

The aim of these questions was to help us design the launch event of the Humanitarian Innovation Fund (HIF)’s Surface Water Drainage Challenge. Over the past couple of months we’ve been working together with the HIF to help them design six challenges in emergency Water, Sanitation and Hygiene (WASH). The scope of this event was to raise awareness of a relatively overlooked challenge in the humanitarian sector, encourage collaborations, and support the development of strong proposals.

This wasn’t the first event we were organising, but it was definitely one of the largest and most open ones. We’re used to designing and running expert workshops where we present a version of what we think a challenge or a prize could look like and then get ready for the experts to tear it apart and help us build a better one. We’re confident with this process as it involves us asking the questions and getting feedback on a clearly defined output. This was something else.

Causes, effects and potential solutions for Surface Water Drainage in a humanitarian emergency.

Surface Water Drainage (SWD) is an important but rarely addressed issue in a humanitarian emergency. Surface water pooling can be a result of storms or overflowing rivers, as well as poor drainage around water tap stands or water tanks. This water can have a major impact on people’s health but also on their self-esteem and dignity. Having to address this problem in an emergency represents additional challenges because of limited funding, available technical skills and time.

Through several rounds of expert engagement and iterations we developed the Surface Water Drainage Challenge Statement. Now, all we had to do was launch it.

The Launch

There are many ways to launch a Challenge. These can range from large public-facing events, to the simple publishing of a call for proposals on a site. Deciding on the best suited approach depends on the aims of the Challenge, the types of solutions sought, likely number of applicants, and the resources available. In the case of the SWD Challenge, we decided to hold a small ideation workshop with key stakeholders and potential applicants (around 30-40 people). The aim was to meet the following objectives:

• Create a shared understanding of the problem: SWD is not a well-understood problem among humanitarian practitioners, let alone those outside the sector. To help raise awareness of this challenge we brought together drainage experts, researchers, consultants, product manufacturers, designers and humanitarian practitioners, to share their experiences, their understanding of the problem, and in doing so, develop a common understanding of it.

• Encourage the development of collaborations: Because of the complexity of the problem of SWD in emergencies, we wanted to emphasize on the need to develop robust and diverse teams with a wide range of skills and expertise that could effectively try to tackle the challenge. By bringing people from different backgrounds in the same room, and encouraging them to think about solutions together, we wanted to facilitate the process of developing successful collaborations.

Ideas generated at the launch can be found on the HIF's SWD Challenge Page and here (.pdf).

• Encourage a design-thinking approach: The HIF were keen to push applicants to think in a more iterative approach about developing solutions. To do so we helped them simplify the application form, made it more concise and emphasized two key elements - user engagement, and learning and adapting. The focus on user engagement implied that involving users in the initial phases of developing solutions was a core requirement, while the focus on learning and adapting asked applicants to think about how to best integrate the feedback received and build upon it. These two elements were also included in the design of the workshop, where participants were asked to come up with potential project ideas, get feedback from the group, iterate, and then receive feedback from a panel of mentors.

• Familiarise participants with the application process: The risk in simply launching a call for proposals is that applicants often have a template form or a specific solution in mind that they will try to fit around the new call. Having a workshop launch meant that we had an opportunity to present the specific details of the challenge, answer questions and give clarifications. We could highlight the types of solutions the HIF were interested in seeing, and the core elements to focus on when submitting the application. Ultimately, the most important objective for the HIF was to receive strong proposals.

Outcomes – Reviewing proposals

A three-week application phase followed the launch event. At the end of this, the HIF received a total of 30 proposals. We were really excited when the HIF asked for our help in shortlisting them. While the review is still under way, there is a clear conclusion we can draw from going through the applications – the stronger proposals came from participants who attended the launch event. These showed a good understanding of the problem and put forward relevant, innovative solutions. They also had concrete strategies for involving users in the initial testing and a plan of how to iterate their solutions based on the feedback.

The common oversight of proposals from applicants who didn’t attend the launch was that they overlooked the ‘innovative’ aspect of the Challenge. While these proposals addressed genuinely challenging drainage situations, the solutions proposed were not innovations and thus didn’t meet the HIF’s funding objective.

Take on the challenge: #innovators needed to tackle Surface Water Drainage in Camps https://t.co/oAgwVd9GOW #funding pic.twitter.com/gy84chi14T

— HIF (@The_HIF) April 12, 2016

To improve on

Finally, while the day turned out to be a success and translated into strong applications, there were some things we could improve on next time around.

• Have the right people in the room: While we made a significant effort to engage and invite people with varying complementary expertise to the launch, we didn’t manage to get a camp planner in the room. The challenges they face and their perspective were missed on the day. Looking ahead, identifying early on key players and making sure they are represented on the day should be a priority.

• Have a good understanding of what attendees know and what they don’t: It came as a surprise that towards the end of the event some attendees were still asking whether funding will be made available for proposals and if so, how will it be allocated. While this information was made available, we think the remaining confusion was due to the fact that almost half of the attendees hadn’t heard of the HIF prior to the event. While this was great in terms of attracting a new audience to the challenge, we failed to acknowledge that it wasn’t immediately obvious that a humanitarian organisation like the HIF would have the available funding to support innovation projects.

• Be flexible with the structure of the day: Remember those post-its at the beginning of the blog? We didn’t need all of them. It turns out that we could have cut out some of the activities we had planned as well. And we did. We made some of them shorter, we removed some, and we made others a bit longer because they were generating really useful conversations. In this process, we learned how important it is to pay attention to the audience, understand what they’re feeling and where they’re at, and be prepared to adjust the structure of the day accordingly.

Looking ahead, we’re eagerly waiting to see the shortlisted proposals and what else this exciting WASH project has got in store for us! In the meantime, we’ll leave you with a short overview video of the launch event:

Unblocking Innovation: Launching the Humanitarian Innovation Fund's Surface Water Drainage Challenge from Elrha on Vimeo.

Shoutouts

Amy - for helping us design an engaging experience and making sure the energy was high on the day.

Maik – for the amazing work on the launch video and getting it ready in record time.

Matteo – for the wonderful illustrations that helped us tell the story of the challenge.

WallaceSpace - for the amazing venue (& the endless sweets!).