Archive for March, 2007

No post for Mar26-Mar30 (out of town)

Tuesday, March 27th, 2007

Quantum mechanics and brain

Friday, March 23rd, 2007

Quantum mechanics in the brain
Christof Koch and Klaus Hepp, Nature 440, 611-612, 2006

I actually read this paper long time ago. It emerged from the pile of papers on my living room floor when I was cleaning, finally, last week. This is an very interesting paper arguing whether quantum mechanics have anything to do with brain or consciousness per se. The authors started with the famous thought experiment — Schrodinger’s box. They designed a little bit different version of that experiment, the observer is looking at a superimposed quantum system (the life status of a cat) with one eye, and at a succession of faces with the other. Then, under certain circumstances, the observer would end up with only being conscious of the rapidly changing faces, in the meantime, that cat is alive or dead is invisible to the observer. So, their reasoning is that although it doesn’t matter whether the observer consciously saw the cat or not, the consciousness is necessary to resolve the measurement (to determine the cat’s fate). Good points.

Further reading:
Hepp, K. in Quantum Future: Lecture Notes in Physics (eds Blanchard, P. & Jadczyk, A.) 517, 92–104 (1998).
Koch, C. Biophysics of Computation: Information Processing in Single Neurons (Oxford Univ. Press, New York, 1999).
Koch, C. The Quest for Consciousness: A Neurobiological Approach (Roberts, Colorado, 2004).
Nielsen, M. & Chuang, I. Quantum Computation and Quantum Information (Cambridge Univ. Press, Cambridge, 2002).
Penrose, R. The Emperor’s New Mind (Oxford Univ. Press, Oxford 1989).


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Paper on chromatin structure

Thursday, March 22nd, 2007

Chromatin structure in the genomics era
Rando, O.J., TRENDS in Genetics 23, 67 (2006) [link]

This is a review paper. The author focus on reviewing the current genomics approaches to understanding chromatin structure and its correlation to gene expression in eukarytoes. Although I have been following and working in chromatin structure prediction for a while, I still can learn a lot from this review, especially, some experimental settings and biologists’ view on these approaches. I believe it is the right way, in order to understand the gene expression to start with chromatin structure (both its static and dynamic status) and then cis-regulators, then networks. However, more experiments targeting each steps/perspectives should be done. This is a good reference paper and I’ll be back on it with more in future.

Paper Assessing the performance of different tiling microarray strategies

Tuesday, March 20th, 2007

Assessing the performance of different high-density tiling microarray strategies for mapping transcribed regions of the human genome
Emanuelsson, O., et. al.
Genome Research 1, 2006 [link]

This paper focus on sorta briefly reviewing different approaches to mapping transcribed regions in human genomes and then assessing them. It is true, arguably though, a detailed comparison of those approaches will ultimately aid the ENCODE Consortium to map transcription at the whole-genome level in various tissues. I found it interesting in a sense of providing a perspective to look at data and the analysis. I’ll discuss more later.

The Fortran developer dies

Monday, March 19th, 2007

It caught my eyes by surprise. John W. Backus who formed the IBM team to create Fortran just died last Saturday. [wikipedia] I still have very vivid memory about my earlier computer studies. In 1994, I had my first intimate touch with computer, a VAX machine per se. That was for practicing a very weird language–a computer language, Fortran 77. We were given 4 hours in a practice class to login in something called my account, change password, and then a couple of VAX commands. I literally spent more than 2 hours on turning on a monitor (terminal), which was very challenging to not only myself but all my classmates (all physicists at that time). At the end of the practice class, I was able to reach the change password part. It was quite exciting and unforgettable, first time in my life I was able to operate a machine without too much labor.

I’d like to quote the obituary in the New York Times [link]:

Innovation, Mr. Backus said, was a constant process of trial and error.

“You need the willingness to fail all the time,” he said. “You have to generate many ideas and then you have to work very hard only to discover that they don’t work. And you keep doing that over and over until you find one that does work.”

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Paper on predicting nucleosome positions

Thursday, March 15th, 2007

Nucleosome positions predicted through comparative genomics
Ilya P Ioshikhes, Istvan Albert, Sara J Zanton & B Franklin Pugh
Nature Genetics38, 1210 – 1215 (2006) [link]

The authors reported that they found sequence signatures of nucleosome positioning in Saccharomyces cerevisiae. The next thing is obvious, using these underlying DNA sequence to predict the nucleosome positions genome-wide. The most useful pattern in their method is that AA dinucleotides are placed facing the histone core complex. Or, in other words, DNA sequences having higher preferences of forming nucleosomes are enriched with AA dinucleotides. The results look good. Anything more could be done?

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Paper nucleosome depletion and active regulatory regions

Wednesday, March 14th, 2007

Evidence for nucleosome depletion at active regulatory regions genome-wide
Cheol-Koo Lee, Yoichiro Shibata, Bhargavi Rao, Brian D Strahl, & Jason D Lieb
Nature Genetics 36, 900 – 905 (2004) [link]

It has been shown that nucleosomes, the basic repeating units of chromatin are depleted in the active regulator regions in various species. This paper is focused on Saccharomyces cerevisiae genome. As one expects, the higher the transcriptional initiation rate, the more likely the nucleosome is depleted at the promoter. The authors confirmed it during the mitotic growth. They also confirmed that in the coding regions of most heavily transcribed genes there is a partial loss of histone H3 and H4 tetramers. One interesting question is then, what would happen for those repressed promoters due to alterations in the global transcriptional program caused by heat shock or a change in carbon source? They did observed nucleosomes recovery in these repressed promoters. Sorta we have circulation of nucleosome switch in transcriptional networks, or, in other words, nucleosome depletion is a critical feature of transcriptional regulation in eukaryotic. I guess it holds for all species as well.

Paper on transcriptional promoters and enhancers

Tuesday, March 13th, 2007

Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome
Nathaniel D Heintzman, Rhona K Stuart, Gary Hon, Yutao Fu, Christina W Ching, R David Hawkins, Leah O Barrera, Sara Van Calcar, Chunxu Qu, Keith A Ching, Wei Wang, Zhiping Weng, Roland D Green, Gregory E Crawford & Bing Ren
Nature Genetics39, 311 – 318 (2007)

This is a very interesting paper and one of the messages is that this genome field is moving very fast and to some extent, purely driven by data. For those like us don’t have the chance to conduct the expensive and innovative experiments, we could only say “WOW”. The authors observed that active promoters are marked by trimethylatoin of histone H3 Lys4 whereas enhancers are marked by monomethylation but not trimethylation of H3K4. Then they went further by applying those signatures to predict promoters and enhancers within the ENCODE regions. The model was validated by that they independently identified regulatory elements with high sensitivity and specificity and also discovered a novel functional enhancer.

I’m going to finish reading and and probably will come back for more discussion if any.

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Mapping DNase hypersensitive sites

Monday, March 12th, 2007

Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS)
Gregory E. Crawford, Ingeborg E. Holt, James Whittle, Bryn D. Webb, Denise Tai, Sean Davis, Elliott H. Margulies, YiDong Chen, John A. Bernat, David Ginsburg, Daixing Zhou, Shujun Luo, Thomas J. Vasicek, Mark J. Daly, Tyra G. Wolfsberg and Francis S. Collins
Genome Research 16:123-131, 2006 (link)

First of all these people are incredibly rich! They have such a facility to mapping the 1% of human genome using sequence tags. Overall, this is a very good approach to study chromatin structure in the genome-wide scale. They created a library of DNase hypersensitive sites (HSs), which end up with 230,000 sequence tags that uniquely map to the genome, and then used massively parallel signature sequencing (MPSS) to identify the DNase HSs. They got 14,190 clusters of sequences that are in close proximity to each other for CD4+ T cells. The validation for their annotation of DNase HSs is from real-time PCR and they concluded that the majority of their DNase HSs are correct. The very next thing is then mapping the DNase HSs to regions which contain regulatory elements, including regions 2 kb upstream of genes, CpG islands, and highly conserved sequences. It is impressive that 80% of the identified DNase HSs map to at least one of those regulatory elements, which could generate some very interesting results.

A question is then, is this annotation actually a cell type specific thing? They answered that most of the DNase HSs identifed in CD4+ T cells are also HSs in CD8+ T cells, B cells, hepatocytes, human umbilical vein endothelial cells, and HeLa cells. Nonetheless, they did find about 10% of the DNase HS sites are lymphocyte specific.

Charleston, S.C.

Saturday, March 10th, 2007

The most emailed stories among the top 10 emailed stories in New York Times is about tour in Charleston, S.C. (link) I did go to Charleston for a vacation and still have very vivid and good memory about the tour. In addition, I got my first cold in recent years. πŸ™‚ Sorta side effect.

In Charleston, I saw some history of US for the very first time. The information center is very helpful, many tour guides there provide plenty of information for visiting those history sites and other attractive events. The tour that I took is for historical buildings. The guide was knowledgeable of what she was talking and introduced us wonderful stories regarding the “colonial ” history of America, rich people’s philosophy–having a “beautiful” house and buried in a church yard,…

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