DIY DNA: One Father's Attempt to Hack His Daughter's Genetic Code
wired.com
wired.com
However, shouldn't he have been able to automate part of the process, if he was manually comparing printouts to the Ensembl reference genome?
The job was daunting: The printouts contained data for approximately 20,000 base pairs, and there was no feasible way to automate the hunt for variants. After putting in a full day of consulting and then getting the kids to bed, Rienhoff would retire to his attic and spend hours checking Beatrice's adenines (A), thymines (T), guanines (G), and cytosines (C) against the Ensembl reference genome.
My understanding is that a simple diff would take care of 90% of the work by eliminating all common base pairs. Then, from the results, his job would be to cross-reference each of the mutations against the gene database. Any unknown mutation could be the one he's looking for.
Perhaps this is actually what he did, and the "no feasible way to automate the hunt" refers to the cross-referencing step, not the differencing step.
Still though, reading that part almost made me email him saying, "I'll find you a way to automate it!".
An example of the zigzag pattern he probably received from the sequencing lab (his would have been much larger): http://www.ensembl.org/Homo_sapiens/Transcript/Summary?db=co...
The reference sequence for the gene (this is what he was looking at): http://www.ensembl.org/Homo_sapiens/Transcript/Exons?db=core...
and his manual diff (at his site): http://mydaughtersdna.org/Members/hyrjr/acvr1b
The usual way to do a gene diff is by aligning two sequences with a program like ClustalW (free, and packaged with Debian now). That shows the differences and positions in a format other programs can read. But I don't know how much annotation the lab gave him, and annotating a pile of introns and exons does take a long time, even with the right tools -- the diffs aren't necessarily helpful until the rest of that information is in place.
The story really hits close to him for me because I have one of the disorders they narrowed out for the poor girl. Like it said, 90% of the battle for surviving some of these is just knowing what you have. It's an overwhelming feeling of frustration and helplessness to have your life 100% at the mercy of a dysfunctional healthcare system. At the risk of using a gratuitous nerd metaphor, this guy's writing his own OS instead of using Windows.
What is more troubling to me is the part of the article stating that he used this to justify canceling the MRI that had been advised by a doctor. I don't have much of a problem with people looking to unconventional medicine when areas that have been well researched have failed. This is especially true when the unconventional methods might have some basis for working and just haven't been studied enough. The problems often start, however, when people turn away from established medicine in favor of the untested methods. I know that he had reservations about that MRI beforehand, but using the gene sequencing to justify canceling the MRI seems to be a step in the wrong direction.
Also, to differentiate diagnoses will frequently take tests and things that normal people don't have access to. A lot of things cause headaches, a lot of things cause nausea (damn near everything does, it seems like), etc. From an information theoretic point of view, it's hard to get enough bits of information from a normal person to diagnose anything. From a Bayesian point of view, it's hard to get enough evidence to diagnose a rare disease starting with low priors, but a system that only diagnoses common diseases is of limited value.
In a limited domain it can do well, or even outperform a doctor (who is also limited by having a large domain, that problem is actually fundamental to the problem space not just the intelligence applied), in general it can't.
I've half-self-diagnosed myself with Celiac disease (wikipedia article is the best on it I've found), which is in the running for one of the most under-diagnosed diseases currently known, precisely because the symptoms are relatively vague and quite variable ("Symptoms include chronic diarrhoea, failure to thrive (in children), and fatigue, but these may be absent and symptoms in all other organ systems have been described." - can it get any more vague? yes, but only barely.). This is an extreme, but there's enough medical conditions like this to make the general case very difficult to deal with.
Self-diagnosis delays consultation with an actual expert. In addition, many symptoms (especially neurological ones) can only be seen or elicited by a trained third-party.
PS: I have a friend with Coeliac disease, so I know something about it. It is hard-to-diagnose conclusively, but that's often not necessary. A key feature of the disease is that treatment, elimination of dietary wheat gluten, is harmless and usually causes drastic improvement. In my friends' case, it didn't, but that's an exception. I strongly recommend talking to a doctor and dietician about it.