Wednesday, March 13, 2013

Gene expression over mutation

The main utility of genetics in health care may be in gene expression not mutation. We have this idea that by knowing our genetic profile we know our genetic disease destiny and can do something special about it. But disease causing mutations tend to either be rare variants with a strong ability to cause a disease or common variants that only slightly increase your risk of disease. If one of this rare strongly disease causing mutations runs in your family you probably know it and you could get tested to see if you inherited it, if you want to know and if there is something you can do about it. But most of us will have the other kind that increase risk slightly.

For example about 4-5% of people will develop an intra-cranial aneurysm, an artery balloons in the brain and has a risk of rupture, during their lives. About 1% of aneurysms rupture a year so most people will live a long life and die of something else, more likely heart disease, than die from the aneurysm. If you come from a high risk family that have a genetic predisposition to aneurysms you have double, 8-10%, life-time risk of developing an aneurysm. And you may also live out your life with the aneurysm still intact. Smoking may quadruple the risk of developing an aneurysm to 16-20% life-time risk, an even stronger risk factor than the genetics.

So what should you do if you have a high genetic risk factor for intra-cranial aneurysms? Don't smoke, control your blood pressure by exercising, eating more fruits and vegetables and less salt, and get regular check-ups. What should you do if you have a normal genetic risk for aneurysms and don't want a 16-20% chance of developing an intra-cranial aneurysm? "Don't smoke, control your blood pressure by exercising, eating more fruits and vegetables and less salt, and get regular check-ups." Sound familiar?

If you have the common mutations that slightly increase disease risk, which is more likely than the rare strong effect mutations, and want to avoid disease (and you actually do want to avoid these diseases) you will do the same things if you have normal risk and don't want these diseases. Prescreening for genetic risks may not make much difference to healthcare.

Many mutations that cause disease happen after we are born. Cancers often start from DNA damage, from the sun, smoking, pollution, diet, viruses, aging, and some may appear to be spontaneous. The immune system may stop many of these cancers early on before we even know we have a tumor. But once they get established tumors often have distinct gene expression profiles.

In a disease like the metastatic cancer glioblastoma certain genes are commonly over expressed and corresponding microRNAs are under expressed. MicroRNAs are short nucleic acids that suppress  genes. Many genes and microRNAs work in balance with the gene up and the corresponding microRNA down. By measuring the gene over-expression profile of a disease and corresponding under expression of microRNAs we could develop treatments by giving the patients small interfering (si)RNAs that mimic the under expressed microRNAs to down regulate the over expressed genes. These patterns of over-expressed (or under-expressed) genes and corresponding microRNA expression patterns could be a key avenue for use to develop highly targeted disease treatments.

Sunday, March 3, 2013

automated software testing

Medical or really any other software should be built with automated testing from the ground up. Unit tests are small test for each unit/class of software. Writing unit test from the beginning of a software project forces the developers to make code more modular and loosely coupled because the unit test runs one class of code in isolation. The unit test also acts as "living" documentation. The unit test shows an example of  how to use the class, and if the unit test works then we know the "living" document is up to date. When developers document source code they often go back and change the source code but not the document leaving a misleading document.

Unit tests are only the first layer of automated testing. Automated tests of the classes working together are needed. These automated tests are more difficult to write but a necessary addition to manual testing.

A manual tester has to run the test the first time to discover the potential problem and then test automation engineers are needed to automate the test because every test has to be reran frequently during development because source code changes can break code that was working before. If we rely only on manual testing we would keep adding and adding new manual tests and we would have to keep adding manual testers who would quickly get bored of rerunning the old tests. Without automated testing the old tests probably just don't get reran because it's too time consuming and dull.

As software developers we really can't say we cannot automate software tests because software development is is all about automation of processes and with medical software it actually could be for brain surgery.

Food work subsidies not food security subsidies

So sugar is looking bad lately, recent studies on diet are showing sugar (cane sugar or corn syrup, it really doesn't matter which) and simple carbohydrates cause diabetes even more than equal calories from other foods. Studies in the New England Journal of medicine are showing the Mediterreanian diet high in fruits, vegetables, nuts, sea food, olive oil and wine protect from heart disease. The last two are, of course, the most popular. 8% of Americans are diabetic and 16% our pre-diabetic so almost 1/4 of Americans cannot process sugar well. 

In response, local governments are banning and taxing sugary drinks and trans fat and they are accused of being a "nanny state". But the first step should be to simply stop subsidizing sugary, carbohydrate laden foods and stop being the treat giving (maybe we should say "granny's cookie") state. Out farm bill provides most of its subsidies to large farms growing corn, corn and more corn, wheat, soy beans and cotton - cotton isn't even food. These programs started in the 1930's to keep farmers employed so it is more of a work program than a food program. Around 98% of America's farmland is used for growing cereals. With so much cereal grown the only way to store so much of so few types of crops is to turn corn into corn syrup and corn oil, wheat into processed white flour, which stores longer than whole grain, soy beans into oil and cotton into cloth. And these subsidies actually reduced the farmland devoted to fruits and vegetables because if farmers take the subsidies they plant fruits or vegetables on the same land. They was to protect the fruit and vegetable farmers from subsidized competition. The result is that our fruits and vegetables are mostly grow in San Joanquin Valley in California and a smaller amount in southern Florida, especially in winter,and trucked all over the continent. This reduces our food security because our nutrition is all grow in a few places. Bakersfield California where the trucks collect has the worst air in America from the truck exhaust and we get our "fresh vegetables" trucked long distance from such a "clean" environment. By simply ending these subsidies farmers would grow more diverse crops as they each try to find a niche to grow crops for the best prices and we would have healthier, more diverse food grown over a wider area making our food healthier and more secure and this actually wouldn't cost us anything except votes from farm communities.