Probing genetic overlap among complex human phenotypes

Andrey Rzhetsky (a collaborator of mine) called me today. Among many things we discussed, he told me that our recent paper on estimating genetic overlap from phenotype data (time at diagnosis) had attracted quite a bit of popularity. It was the 24th most read paper of PNAS for the month of July 2007. And it was covered in MIT technology review and the Wired Science blog, among many other more biomedical related sites. Besides nice graphics, the paper used time-to-event models to estimate potential genetic overlap between human disorders.

Correction: Chair Mao didn't say everything after all.

As Li pointed out, I had the wrong memory. I never aced any of these courses in my school days. BUT, I should have GOOGLED!!! :) That saying was published on May 11th, 1978. However, it was not proposed by Deng Xiaoping, despite the common perception. Deng only publicized it a lot. This is again a good example of Stigler's law of eponymy.

Chairman Mao was right!

I did not grow as a generation fully influenced by Mao Zedong. Actually, several days after I was born, he passed away. However, we still got to study quite a number of his quotes. One of them is "practice is the only way to validate the truth" (pardon my unpolished interpretation). 实践是检验真理的唯一标准。I have never given this quote much thought before yesterday.

Yesterday, I received an email regarding a computational biology challenge. The contestants are supposed to analyze the data and discover the gold standard genes or gene-gene interactions hidden in the data. This is a blinded challenge and the results will be announced during the conference. A winner will be named.

I was intrigued. For a couple of the challenges, I thought of some ideas. I thought, my methods might actually work well. "Shall I enter this contest then?" I asked myself. Then, it suddenly worried me that what if the data do not agree with my assumptions for my method. "That would really be a problem!" I thought, "and I might be at the bottom of the contest." But then it hit me: it would actually be nice that the method doesn't work and we understand which assumptions are wrong. How else can we learn about the biological systems if we don't fail?

This reminded me of my struggle with a simulation study recently. Part of the phenomenon I observed does not agree with my intuition. At first, I kept debugging my codes. But the codes were so short that I was finally convinced that what I observed was a true phenomenon of the statistics I was evaluating when the dimension is too large.

Often, I judge the validity of a method first by intuition. These recent experiences show that knowledge can actually occur when the intuition fails. And intuition is just knowledge based on past failed judgements. Therefore, Chairman Mao was right about one thing, if we don't just do it and fail, we can't learn the truth. Sometimes, it is necessary to make a fool out of ourselves for the greater good---better knowledge for the mankind. :) Or we can just have one more reason to feel less grumpy whenever we fail.