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.