A spotlight on the gut at XSEDE'13

Possibly one of the most literally ‘in-depth’ talks I’ve attended at a computing conference came from Larry Smarr of the J. Craig Ventnor institute. He has got involved in biomedical research in the most personal way possible – by presenting his microbiome, or microbial profile, to be scrutinised in minute detail by researchers. The body has 10 times as many microbe cells as human cells. In fact, 99% of the DNA in your genome is in microbial cells not in human cells. “Topologically we’re a torus”, said Smarr. “Effectively, the bugs are all on the outside of your body, including your guts.”

Smarr’s interest in the microbiome started with increasingly severe but misdiagnosed stomach problems. Smarr was not impressed with the guesswork involved in treating his symptoms. He thought DNA sequencing should give a much more accurate picture of what was going on, eventually leading to a diagnosis of early Crohn's disease, an inflammatory bowel condition. With the cost of sequencing a genome fallen from 4 billion dollars per genome, to 4000 dollars, financing the research is not so much the issue – it’s picking out the microbial from the human, and then identifying what you have left. Research using the Gordon supercomputer at SDSC still found a significant proportion of DNA that was ‘unknown’. 

What is clear though is that Crohn’s disease has a devastating effect on the gut bacteria – the equivalent to a ‘mass extinction event’ in Smarr’s words. The traditional medical approach of waging war on the gut microbes using heavy duty drugs was not going to help – the better approach is to switch from full frontal attack to ‘gardening’. This means using new therapeutical tools to manage the microbiome and encourage ‘good’ bacteria. Diet is also an important factor. “Change the feedstock and you’ll change the shape of the garden,” advised Smarr. As he’s still donating all sorts of raw materials to the research programme on a regular basis, he should know.

(You can read more about microbial gardening on the CNN website – even the Economist has got in on the act with its cover page article ‘Microbes Maketh the Man’)

Biosciences Day at XSEDE’13 closed with a lively panel session featuring speakers from a range of high tech biomedical companies, including at least one lawyer. This is not as strange as it first sounds, because many of the issues affecting biomedical research come down to the ethics of sharing very personal data. “If you surprise a bioethicist with a question, the answer is always no” said Glen Orter of Dell. Alex Dickinson of Illumina Inc looked at the role of cloud computing in genomics, including two killer apps – whole genome assembly and variant calling, as well as single click sharing of very large data sets. His wish lists included cloud bioinformatics featuring openness and collaboration. “Interpretation is now the key, since analysis is no longer the bottle neck,” said Dickinson. This means thinking big and looking at phenotypes (how genes are expressed in the body) not just genotypes. “We want whole genomes and lots of them,” he announced.

Donald Jones of Qualcomm life talked about connected data, from wherever it orginates, inside the body, outside the body or from instruments. To bring in a Star Trek reference, this is the ‘tricorder challenge' to find simple to use multimeters for monitoring the body, like the blood glucose meters already used by diabetics. In the future, we’re likely to see increasing numbers of health related apps.
 

Darryl Leon from Life Technologies advised us to think holistically and also address the environmental costs of intensive computing – can we have low energy high energy computing? Nicholas Schork from the Scripps Institute said that sequencing genomes might be cheap at a few thousand dollars but interpretation can cost many times that amount. There are 4-6 million variants per person to explore using algorithms. “This is computationally intensive, and they may not do anything in the end or contribute to disease,” said Schork. There are a host of so-called idiopathic diseases where the cause is still unknown. Increasingly, the “exposome” will become important as well as the basic genome – the exposome is everything you’re exposed to in your life, including environmental factors. The more data we share on the exposome, theoretically the more information can be gleaned to lead to new treatments

The panel speculated that we might eventually see the equivalent of Facebook for sharing personal medical data – would you share your genome as blithely as as your holiday photos? But what about genetically identical twins where only one wants to publish their data, and the other prefers privacy?  Data might be compressed and encrypted – but this doesn't necessarily offer a full protection. Some people with Crohn's, like Larry Smarr, publish all their data in the hope of helping to find a cure. But others want total privacy – the challenge for the future will be to find a way to tread both these paths.
 

Biosciences Day at XSEDE'13

After the excitement of the XSEDE’13 kick-off next door to Comic Con, and the glamour of a 1940’s themed Chair’s dinner aboard the USS Midway, we moved into Biosciences Day. Touring the Midway, we squeaked across the blue and white checked lino of the mess deck (hearty hot meals were served 23 hours out of every 24) and ducked into the cramped confines of the sick bay with its three tier stacked bunk beds. The operating theatre and dental surgery were right next door to the machine shop. To the untrained eye, the equipment in all three looked broadly similar. (Given the gender bias of the crew, I’ll leave the identity of the two most requested elective operations to your imagination. They weren’t on the teeth). The basic nature of the medical treatment on offer to the crew however was a timely reminder of how far medicine has come in the last half century, particular now that high performance computing has joined the medic’s armoury.

David Toth, a Campus Champion at the University of Maryland Washington, talked us through the role XSEDE resources have played in finding potential drug treatments for histoplasmosis (a fungal infection), tuberculosis and HIV. In the days of the USS Midway, crew with a positive HIV test were immediately air lifted to shore, with a future behind a desk rather than at sea ahead of them. Toth’s group screened 4.1 million molecules using XSEDE resources, a task that would have taken 2 years on a single desktop PC. Some drug candidates are now being tested in the wet lab, with several promisingly showing the power to inhibit cell growth. “Supercomputers do a great job of outpacing the biologists,” said Toth. One enterprising feature of the work was that students each screened 10,000 molecules as part of their course, with one student striking lucky with a potential drug candidate.

Looking at biomedical challenges more broadly, Claudiu Farcas from the University of California in San Diego summarised some of the issues posed by data. For a start, there are many different kinds of data, from the genotype, RNA and proteome, on to biomarkers and phenotypes, right up to population level data, all with their own set of acronyms. Public repositories are often poorly annotated and are mostly unstructured as well as governed by limited and complicated data use agreements. “Researchers are encouraged to share but are not always enabled to do so,” warned Farcas.

A particularly thorny issue for biomedical data analysis is how to deal with sensitive personally identified information (PII). Researchers need to protect the privacy of patients by anonymising their data. It also needs to be cleaned up, compressed and aggregated so it can be analysed efficiently. But how best to do this? Bill Barnett, of Indiana University said earlier that biologists really don’t care what they use, as long as it works. Cloud computing can be tempting, but institutional clouds are often still at the early stages of being set up, and commercial sources might have “questionable” privacy protection.

The iDASH (Integrating Data for Analysis, Anonymization and SHaring) portal allows biologists to focus on the biology, not the data. It includes add-ons such as anonymisation of data, annotation, processing pipelines, natural language processing, and the possibility to preferentially select speedier GPGPU resource. According to Farcas, iDASH offers a secure infrastructure plus a platform for development, services and software, including privacy protection.

XSEDE’13 in San Diego – when super heros met supercomputers

There aren’t too many conferences where you meet Batman, Dr Who and the Wicked Witch of the West while still checking into the hotel. XSEDE’13 in San Diego this year overlapped with the famous Comic Con event right next door – so caped super heros marching past in the lobby was apparently part of the deal. Comic Con attracts over 120,000 participants every year, XSEDE slightly fewer at 700. But this is an ever rising number year on year, as project leader John Towns was pleased to point out. And I have a suspicion that the categories of ‘comic book nerds’ and ‘IT geeks’ are perhaps not entirely mutually exclusive sets…

XSEDE, the Extreme Science and Engineering Discovery Environment, is a National Science Foundation-supported project that brings together supercomputers, data collections, and computational tools and services to support science and engineering research and education. The annual XSEDE conference focuses on the science, education, outreach, software, and technology used by the XSEDE and other related communities worldwide.

The programme kicked off with a day of well attended tutorials – with a 200-strong host of students at the event, the training opportunities were well appreciated, as was the opportunity to showcase their work in poster sessions and competitions. Even younger participants were catered for by a morning robotics class, “Ready, Set, Robotical” which I was more than tempted to join.

Training is always a strong theme at XSEDE, and the challenges of providing online courses in parallel computing were discussed, as well as developing undergraduate and graduate programmes in computational science. Campus champions are the backbone of outreach on a regional basis, and XSEDE is now looking to expand the scheme into subject specific champions. This emerged as a theme for future collaboration between XSEDE and the European Grid Infrastructure in the Birds of a Feather session. EGI recently set up an EGI Champions scheme, including representatives from fields as disparate as life sciences, environmental sciences and maths. Other areas where EGI and XSEDE expect to work together include federated high throughput data analysis, federated clouds and user support. One use case already in progress covers HPC-HTC workflows for the computational chemistry community. This was one of the joint use cases that emerged in the call issued at the beginning of the year. So there's lots to watch out for, even now the caped crusaders have (mostly) left town.