Animal vs. hunter

An animal hided in the forest, and felt so dangerous because of the frequent visits of the hunter. One day, the small animal couldn't stand the hiding, stood out, and asked:" why are you consistently hurting me?" The hunter paused a moment... and said, "I shoot you because ....you look dangerous!" hahahaha...

Take and Give

I seldom admire someone, but the grace words from a lady before the end of her life really touched my heart. I felt not only the calm and grace attitude facing the death, but a strong heart that embraces a lot of loves and also has such a capability to give. A heart that is capable to give makes her last life so beautiful. Many people may be used to take, but seldom think to give. Or may put it a lower priority. Frustration may appear then.

The marriage vows during the wedding are the beautiful wishes for every couple who possess love from the starting point. Yet the glamor may fade as more true colors of life appear. Difference to the dream may produce all types of additional dramas among people. The more you require yourself, the more you want from your love and life. However, you don't want to deny that people do possess love, no matter what.

Maybe, free each other a little bit. Not always think of what you can get, but how much you can give. The hot energies in this world will be exponentially increased (do some math...) hahahaha...The ones with love are always blessed!

Bless the free hearts!

Live in Grace

There is a path to the paradise for everyone. In daily life, we are busy. "So we just work until we die?", as a bee asked in "bee movie". I guess it looks like so. Busy-works make lives, but also may lose yourself.

When you stood among people, you can find that some faces are cheerful because of promotion, love, or youthful innocence, and some faces are light-less because of burden, work, or broken heart? What do you want to look like? An energetic and charming person? Only the appearance attraction to cheer up people's eyes like the role of a celebrity or super model, or just a moment of enchanting for yourself?

Once upon for a time, we are educated to be grace. We need walk stably without peeking, we need eat quietly, and we need to talk slowly without loud laugh. There is a picture for the little ones that something wonderful in their mind. What are "the wonderful" things and how "wonderful"? Always unlimited imagination space to lead you work for it.

I am fascinated in the essence instead of superficies. People are easy entertained by eyes, and beautiful things are lovely. However, I questioned how much happiness and satisfaction A GRACE OUTSIDE can bring to people. Anything has double sides. The most beautiful face is usually the one wearing the enchanting smile from inside to outside. However, THE GRACE INSIDE needs a strong heart.

I don't want to say, hi, let's live in grace, no matter what happened in your life. Everything can be easy to say than done. I just want to say that, when you lose yourself in life, remember to strive for grace.

Fun song

Had a glance of glee show last night. Impressive a beautiful song they sang. Found out that it's Train's "Hey, soul sister". Good to see youthful energy from the choir. Here is the link for glee's version: http://www.youtube.com/watch?v=X-Ysqz_sMU0
Just don't understand one thing: how could the feeling to soul sister be comparable to a virgin to Madonna. Guess I got culture gap here. hahahaha...

Attitude to Life

Rather moody these days. Guess I can put my thoughts and views into a drama if I like. Still, the words here can only be the abstract and summary words. Usually, when such words means (1) a wise, (2) no time to write out the whole story, or (3) something that's better not to say directly. Guess I can never be a wise, but want to write something which is actually rather scattered.

I experienced a bunch of things in the last month. In addition to attending two meetings, I visited back to China after so many years. A lot of feelings especially when I saw my family. Met my old classmates and friends. Saw many faces and new phenomenon.

Then I'm back. Put aside the feeling about back to China now. I want to only ask one question here: what's the people pursuing in their life?

When I tried to cheer for the constructive future for my classmates during one of our dinning meetings, one of high school classmate stood up and said: let's be happy once we live one day. My high school teacher said, we live for our families now when we're in forties. I guess I carried such questions until today when I'm back. When I sat alone by myself at my office, my work room, I actually don't want to say the cheerful words during the dinning meeting ---"let's do something meaningful to everyone of us, to this society, and to our next generation...", I just want to ask myself which is hidden in the corner of my heart, what do you want for your life?

Guess the best ending is to stop here.

Copy a poem that I read before

Love a sad poem that I read long time ago (http://www.rpi.edu/~jix/disclaimer.html), and copy it here.

The furthest distance in the world

Translated by muyv

The furthest distance in the world
Is not between life and death
But when i stand in front of you
Yet you don't know that I love you

The furthest distance in the world
Is not when i stand in font of you
Yet you can't see my love
But when undoubtedly knowing the love from both
Yet cannot be together

The furthest distance in the world
Is not being apart while being in love
But when plainly can not resist the yearning
Yet pretending you have never been in my heart

The furthest distance in the world
Is not (you have never been in my heart)[1]
But using one's indifferent heart
to dig an uncrossable river
for the one who loves you

The impression of GAW 17

An interesting thing happened at the first day of GAW 17 presentation. The group discussing collapsing methods announced that the collapsing methods don’t work. Two questions come out quickly. One is from Qunyuan Zhang (working with Michael Province). He basically asked whether such announcement is proper since so many works about collapsing methods have done and published. We also got pretty good results using collapsing schemes, so I asked another question, did your group members test on pathway level? If not, whether it’s because of the problem of collapsing methods or the genetic units.
Now, it turns out people are interesting on the tests using signaling pathways. Actually we did the tests on SNPs and Genes level, we didn’t get good results except two genes either. We didn’t do type I error and power tests because of the tight timeline. So two groups are interested in asking me to join in now. I may join the group with more signaling pathways based approaches to see whether I can get more helpful information.
The good part of the meeting is that people are working on the same dataset and you can see the position of your work among people. The bad part of the meeting with many junior discussants is that they can make some rather basic mistakes.
It seems most found only FLT1 and/or KDR which can be found using Plink. We detected these two genes significantly as well. In general, our work maybe among one of the qualified ones. People are crowed in front of our poster until the late of the next session.

The rest day is much easier since the similar works are distributed among the different topics. The impressive one is that Robert Elston and one group presented their work using the style similar "are you smarter than a 5th grader?" Another group used cartoon movie which is very interesting. Good to meet and communicate with all types of people who are working with you in the same field.

IGES meeting

IGES is finished today. Try to write down something before I may forget.

IGES oral presentations include many interesting topics including rare variants, secondary phenotype, gene pleiotropy, multiple phenotypes, gene-gene interactions, gene-environment interactions, and signaling pathways. I list some about rare variants and secondary/multiple phenotype discussion.

Though it's still early, it looks that people has started to work on mapping rare variants that are associated with diseases. I noticed that there are interesting and new methods about rare variants. Particularly, a work from David Conti and his student considered two directions when collapsing rare variants. A work from Qunyuan Zhang and Michael Province used p-value based sum which considered both the significance and the direction of rare variants. The work from Joon Sang Lee et al. also tried to identify the optimal pooling size for rare variants.

A secondary phenotype from J Wang and S. Shete considered the problem differently from ours. We and the ones including Danyu Lin considered the secondary phenotype conditional on the primary disease status. However, this work tries to correct the bias that may be brought in if consider the secondary phenotype as either a case or a control. There are also a bunch of studies about multiple phenotypes. This intrigues me to wonder whether the problem of multiple phenotypes should include the problem of the secondary phenotype. Or any inherent connection between them.

People used a lot of linear or logistic regression based models by adding more variants including GXG, GXE and others. A simple mind comes up: can we get better models instead of only logistic or linear models?

People also tried to use Bayesian to do some works. According to my observation, most people used Bayesian is only for the convenience of calculation. The strategies of incorporating prior information are not that mature now.

IGES first day impression

The theme of first day workshop is “Next Generation Sequencing (NGS) in Genetic Epidemiological Studies”. Besides academic people, the presenting panel also includes people from companies such as Affymetrix, Illumina, and Gold Helix. The talks are interesting especially the ones from Suzanne Leal and Scott Williams. Scott talks about NGS from evolution point of view. Suzanne’s talk is more related to our works.
Suzanne’s talk basically reviewed the papers what we discussed in Journal Club and our GAW 17 submission abstract including
Cohen JC, Kiss RS, Pertsemlidis A, Marcel YL, McPherson R, Hobbs HH. (2004) Multiple rare
alleles contribute to low plasma levels of HDL cholesterol. Science,305,869872.

Madsen BE and Browning SR. (2009) A group-wise association test for rare mutations using
a weighted sum statistic. PLOS Genet, 5(2), e1000384.

Li B and Leal SM. (2008). Methods for detecting associations with rare variants for common dis-
eases: application to analysis of sequence data. Am J Hum Genet., 83(3), 311-321.

Morris AP and Zeggini E. (2010) A evaluation of statistical approaches to rare variant analysis
in genetic association studies. Genet Epidemiol 34(2), 188-193.

Price AL, Kryukov GV, de Bakker PI, Purcell SM, Staples J, Wei LJ, Sunyaev SR.(2009)
Pooled association tests for rare variants in exon-resequencing studies. Am J Hum Genet., 86(6),
832-838.
Another one she mentioned is her new work named KBAC (didn’t write down the whole name). In this work, the basic idea is to upweight the causal genotype. She also tested it upon gene interaction. I asked two questions here for her new work. (1). How to distinct causal genotypes from non-causal ones, especially in real data, and how distinct it from functional genotypes since she also mentioned that they are different. (2). How did they simulate gene interactions? For (1), she responded that, in simulation, they know whether the genotypes are causal or not. But in general in real data, there’s no way to distinct. For (2), she used some data that are known to involved gene interactions. That is to say, they use the known information.
She also pointed out several challenging problems in this field. I list some here: (1). Population structure/admixture, (2) gene X gene, gene X environment, (3) Signaling pathways, (4) Jointly analyzing rare and common variants, and (5) qualitatively and quantitatively.

Touching words

Sometimes feel heart can be tired to get some things through. Occasionally, found pieces of words from a small notebook,

"The world is bound to no man
Little drops of water,
little grains of sand
make the mighty
ocean and
the pleasant land."

Whether I can bound my heart between the sky and the land, and have a moment of peace?... (I have uncertainties to ocean, so I'd rather put me between the sky and the land)

On the corner of the small notebook,

"You are the only one that fills my heart."

Different people have the different reasons to fill the different persons to their hearts. However, I'm happy there is a one for many people so that life can look beautiful sometimes.

A moment of peace between busyworks

Jammed between works. Deadline came, changed, and working on the final version. I'm done the feedback modification boss brought to me. His meeting is still going on. What can I do now? Other works... too less time for too much work. Lunch... God, forgot the wallet at home this morning. Maybe just a moment of break... so precious. Print another small picture for my baby. Always happy to see his smiling and heartless face.

So just dance

I feel I am pretty productive recently, though still have pressure to get papers published. It's already Sep. I got one rather good work rejected, mainly because they feel the topic is not so right to their journal. I have another finished work under modification. I have another rejected paper ready to polish. I just finished the work for GAW 17. Of course, I have some other collaborating works going.

It looks everything is busy, but I need to push them, make progress and get things done. Hard work, sadness, mixed of hope. Sometimes, I feel I can't keep things alive, and just want to have a good break. But who can't tell that everyone who keeps good wishes is not experiencing the similar feeling.

A moment of numb. Maybe, I can just ignore the details. Have a moment of peace, with my little sweet man, to listen to the piano. So why not just dance, and maybe you may find you can be just ok or just be wonderful without the need of counting the good and the bad.

Methods of collapsing rare/common variants for mapping the assocition to traits in next generation sequencing

The time of next generation sequencing (NGS) comes so quick, and all of the sudden all the meetings and journals are ready to welcome for NGS time. This reflects to our research as well. I submitted a grant with transferring the concept of joint analysis of family and unrelated data to NGS. Then we quickly merged to 3 NGS projects.

Non-enough of explaining the most mapped common alleles to common diseases, people swarmed to rare variants. However, some rare variants will explain the disease, some may not since many of them are maybe only the results of evolution. Besides, due to its rare occurrence, larger sample size is needed to draw statistical conclusions. Yet many of the rare variants may occur as random mutations and be rare to repeat in population. All of these made the association study more difficult.

We reviewed the recent papers about rare variants. But most used the simulated data including Li and Neal,AJHG, 2008, Madsen and Browning, PLOS genetics, 2009 and Price et al. AJHG, 2009. The basic idea is that people are trying to upweight the rare variants that have true associations. It also seems that a bunch of GAW17 people are working on the same or similar topic. Obviously, it is worth to dig something here. But I have some little concerns whether it's worthy to draw so much attention?

Analysis of GAW 17 data

GAW 17 data comes late this year. So people were rushing to make the coming deadline. We proposed a rather conservation method to analyze the data, however, the results do not look good in the first place. It took a while to observe from every aspect that it doesn't turn out the signal, with the accompany of the feeling of missing the deadline.

As more and more tests turned out not to be positive. I started to examine and analyze all the possible reasons. Though, all types of analysis look reasonable, but people don't have good ways to solve these problems. For example the influence of low heritability to the mapping of snp variations especially including the rare ones in NGS to traits.

This morning, I felt I may need to start a series of tests that may enlarge the signal units. Instead of genes, maybe signal pathways, since so many genes have only one or two rare variants, and it doesn't make sense to get anything from them.

Then, may change the view of extracting information. Not only use one rule, but may use multiple rules to collect information. Cross my figures...

Go to Lake Jordan today

We will go to Lake Jordan today. Since we moved to here, didn't really get into it. I also feel I need a break from work. Though, I'm still trying to work a little bit this morning. What's the feeling if I can completely cut off work for a moment?