StatGene Research Group Blog

NYTIMES: From one genome, many types of cells. But how?

2009-05-19T12:27:00.006-04:00

This is a nice article in NYTIMES talking about the complex nature of genetics.

Some good readings on important trends in statistical genetics

2009-03-21T21:42:00.004-04:00

I. OVERVIEW
1. Science 7 November 2008: Vol. 322. no. 5903, pp. 881 - 888
Genetic Mapping in Human Disease
2. Nature Reviews Genetics 10, 241-251 (April 2009)
Human genetic variation and its contribution to complex traits
II. Association Studies, especially GWAS
3. Nature Reviews Genetics 9, 356-369 (May 2008)
Genome-wide association studies for complex traits: consensus, uncertainty and challenges
4. Nature Reviews Cancer 4, 850-860 (November 2004)
Association studies for finding cancer-susceptibility genetic variants
III. Challenges of associations studies (interaction, population
stratification, etc)
5. Human Molecular Genetics, 2002, Vol. 11, No. 20 2463-2468
Epistasis: what it means, what it doesn't mean, and statistical methods to detect it in humans
6. Nature Genetics 37, 1243 - 1246 (2005)
Population structure, differential bias and genomic control in a large-scale, case-control association study
IV. LD and Haplotype block
7. The American Journal of Human Genetics, Volume 69, Issue 1, 1-14, 1 July 2001
Linkage Disequilibrium in Humans: Models and Data
8. Nature Reviews Genetics 4, 587-597 (August 2003)
Haplotype blocks and linkage disequilibrium in the human genome
V. Selected methodology reviews
9. The American Journal of Human Genetics, Volume 78, Issue 3, 437-450, 1 March 2006
A Comparison of Phasing Algorithms for Trios and Unrelated Individuals
10. The American Journal of Human Genetics, Volume 74, Issue 5, 979-1000, 1 May 2004
Methods for High-Density Admixture Mapping of Disease Genes

Reference for Tim's presentation

2007-10-05T11:19:00.000-04:00

History of human genome project:
http://www.sciencemag.org/cgi/content/full/291/5507/1195

Science paper:
The sequence of human genome
http://www.sciencemag.org/cgi/content/full/291/5507/1195

The international hapmap project
http://www.hapmap.org/downloads/nature02168.pdf

Properties of linkage disequilibrium
http://www.pnas.org/cgi/content/full/99/26/17004

SNP discover (a presentation)
http://wheat.pw.usda.gov/ITMI/RafalskiXITMI2/index.htm

Let me know if you would like to know other topics along this line and I will find more references.

Group meeting [Sep.28.2007]

2007-09-28T13:29:00.000-04:00

Today we discussed the dpGaP data sets.

1. [Tian] Even though we have been granted the access to the data, I don't think the data files are available. We submitted archive request online but the status of those requests has been "preparing". Another clue was for only one of the three studies, the file sizes were known, which was huge.

2. [Yuejing] Two papers were listed as reference to the Major Depression data but only one was available. [Yuejing] found a presentation file from UNC which updated the status of the study. The study screened families that participated in a Netherland study on MDD over the span of 10 years and selected those with concordant twins with extreme high or low trait values, and discordant twins with sharp contrasts (high <-> low). Linkage results from previous studies show little overlap. The sample size described on dpGaP differs slightly from the presentation file.

3. [Chien Hsun Huang] searched for "Nephropathy" and Type I diabetes and found there are not many papers on this topic. Little is known about its genetic component, we can only assume.

A little background: Nephrotic syndrome is a disorder where the kidneys have been damaged, causing them to leak protein from the blood into the urine. It is characterised by proteinuria (>3.5g/ day) hypoalbuminemia, hyperlipidemia and edema. Diabetic nephropathy (nephropatia diabetica), is a progressive kidney
disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and nodular glomerulosclerosis. It is due to longstanding diabetes mellitus, and is a prime cause for dialysis in many Western countries.

The reference paper describes the study data and design without any analysis results. The most important point is that this study has three designs (case/control, case-trio and control-trio) which could be an advantage for results validation but can also cause interpretability difficulty as the authors discussed.

There is one recent paper from Nature that identifies a Type I diabetes gene.

4. [Jun and Tian] The ADHD data might be the first data we can get our hands on. The 2006 Molecular Psychiatry paper outlines the recruitment of subjects. The data came from a multi-center study involves eight countries. This might create some population structure issues. However since this data set consists of only case-parent trios, the impact of population stratification is not of concern. Despite its high heritability, there has not been any identified genes for this disorder. Previous genome scans didn't have much overlapping significant results. In the 2006 paper, candidate genes were study and only nominal significant results were obtained for 7 out 51 genes. The 2006 Behavioral and Brain function paper described the genome scan efforts using the same sample of subject. It outlines the plan of this project. 600,000 tagging SNPs are to be used. Gene-gene interactions should be considered. Gene-environment interaction may play an important role for this disorder but is hard to account for in analysis. One thing we might try first is to construt a candidate gene study first.

5. Next week, we will check the data status. We will also go over some review papers in genetic epidemiology (see the last post) for Jun, Bo, Julia, Chien-Hsun.

[Reading list] Background reading on statistical genetics

2007-09-28T12:41:00.000-04:00

Here are papers we want to discuss for next Friday.

If you have difficulty accessing the PDF, please let me know.

1. Nat Rev Genet. 2001 Feb;2(2):91-9.
Association study designs for complex diseases.
By Cardon LR, Bell JI.

2. Nat Rev Genet. 2005 Feb;6(2):95-108.
Genome-wide association studies for common diseases and complex traits.
By Hirschhorn JN, Daly MJ

3. Lancet. 2005 Sep 24-30;366(9491):1121-31.
Genetic association studies.
By Cordell HJ, Clayton DG.

4. : Lancet. 2005 Sep 17-23;366(9490):1036-44.
Genetic linkage studies.
By Dawn Teare M, Barrett JH.

5. Am J Hum Genet. 1996 Nov;59(5):983-9.
The TDT and other family-based tests for linkage disequilibrium and association.
By Spielman RS, Ewens WJ.

Group meeting [Sep.21.2007]

2007-09-21T18:05:00.000-04:00

Last Friday, we held a research open house for PHD students and visitors. In the future, such format might be turned into a regular research club of some sort.

Today, two MA students joined our group meeting.

Bo Qiao. A recent graduate from Tsinghua University.
Chien Hsun Huang (sound). A statistical genetics researcher from Taiwan

Iuliana visited us today. We discussed the possibility of her visiting us monthly, supported by our newly funded NSF/NIGMS grant.

Dr. Jun Xie (associate professor from Purdue University) is visiting our department and would like to participate in our research for this semester. Welcome!

We discussed the three data sets that were granted to us from NCBI: genome association studies on major depression, type I diabetes, and ADHD. These three sets have very different data structure. We will study the background information of these studies in the coming week and will discuss how to analyze them during next meeting.

Major depression: Ding and Lo
Diabetes: Qiao and Huang
ADHD: Zheng and Xie

It is nearly unthinkable that we still have confusion over the meeting time. And we now decided that we will meet at 10:30 on Friday in Room 901, until further notice.

Group meeting [Sep.07.2007]

2007-09-07T18:28:00.000-04:00

It is the first meeting of this year. Also the first time Tim and Hugh joined the group meeting. We discussed the following items

Apply for available genetic data: we have applied for several sets of genetic data and are waiting for board approval.
Hugh reported his study on subset coverage issues in his computing.
We discussed new research problems related to true signals and "imposter" signals and how to deal with them.
Next week, we are going to have research open hour for PHD students and visiting researchers to our department.

Our GAW papers outcome

2007-04-13T13:59:00.000-04:00

Originally we submitted 4 papers. After the GAW meeting, we merged two related papers, Ding et al. and Cong et al. into one combined paper. It was pointed out by others during the GAW meeting that these two papers shared a common theme (both used association information in our BGTA method and both returned an association network among loci identified) even the scope and scale were very different (one genomewide and the other is on 20 SNPs in 14 candidate genes).

Therefore, we submitted three papers for peer-review to be published in BMC Genetics Proceedings on GAW 15. Zheng et al. was accepted with minor revision in the first review. Ding et al. (merged paper) and Ionita-Laza et al. both received some very constructive comments and were subject to revision. The flexibility of our methods and interesting results were recognized by the reviewers. It was also pointed out by one of the reviewers that our analyses targeted to give a comprehensive analysis of the GAW15 data, which was not very common among this year's contribution.

Due to health reason, Iuliana didn't finish the revision. The revised Ding et al. was accepted in the second review.

The following two papers from our group will appear in BMC Genetics Proceedings of GAW 15:

Ding, Y., Cong, L., Ionita-Laza, I., Lo, S.H. and Zheng, T. (2007) Constructing Gene Association Network for Rheumatoid Arthritics Using the Backward Genotype-Trait Association (BGTA) Algorithm. BMC Genetics. Accepted.

Zheng T, Wang S, Cong L, Ding Y, Ionita-Laza I, Lo SH (2007) Joint study of genetic regulators for Expression Traits Related to Breast Cancer. BMC genetics. Accepted.

Blogger moved to google

2007-04-13T13:56:00.000-04:00

Blogger was changed to a new blogger by google. For a while, no new post can be posted since Google requires all admin log in and agree to Google's terms. It took us a while to get it done. :)

Happy 2007

2007-01-29T10:29:00.000-05:00

Just want to blog here that we have submitted our GAW papers early January. They are under peer review. Our GAW posters are now wall decoration in the statistics department.

Our GAW 15 contributions

2006-10-04T10:01:00.000-04:00

Joint study of genetic regulators for Expression Traits Related to Breast Cancer
Tian Zheng, Shuang Wang, Lei Cong, Yuejing Ding, Iuliana Ionita-Laza, and Shaw-Hwa Lo

A Comprehensive Analysis of Association between Several Candidate Genes and Rheumatoid Arthritis in Samples from North American Rheumatoid Arthritis Consortium (NARAC)
Lei Cong, Tian Zheng, Iuliana Ionita-Laza, Yuejing Ding and Shaw-Hwa Lo

Constructing Association Network in Two-Stage Analysis: An application of Backward Genotype-Trait Association (BGTA) Algorithm to NARAC Data
Yuejing Ding, Tian Zheng, Iuliana Ionita-Laza, Lei Cong, and Shaw-Hwa Lo

Combined Linkage and Association Analysis of the NARAC Dataset
Iuliana Ionita-Laza, Yuejing Ding, Tian Zheng, Lei Cong, and Shaw-Hwa Lo

GAW 15 progress

2006-07-18T11:45:00.000-04:00

We are currently working on 4 projects
(1 for problem 1 and 3 for problem 2).

Important dates:

7/28 deadline for questionnaires
9/12 deadline for report (max. 5 pages)
11/12-15 GAW 15 conference in Tempa bay, Florida

Pedigree-drawing with R and graphviz

2006-04-13T09:28:00.000-04:00

Bioinformatics Advance Access originally published online on February 17, 2006
Bioinformatics 2006 22(8):1013-1014; doi:10.1093/bioinformatics/btl058

Jing Hua Zhao

MRC Epidemiology Unit, Strangeways Research Laboratory Cambridge CB1 8RN, UK

Summary: Two functions for pedigree-drawing available in R (http://www.r-project.org): plot.pedigree in kinship and pedtodot in gap are described. The latter requires graphviz (http://www.graphviz.org). They can produce many pedigree diagrams quickly into a single file, serving as alternatives to programs that only offer interactive use.

Availability: Packages kinship and gap are available from http://cran.r-project.org.

Contact: jinghua.zhao@mrc-epid.cam.ac.uk

Group meeting recap [4.7.2006]

2006-04-07T12:02:00.000-04:00

0) We need to looking to machine learning literature to find current discussion/proposals on comparing different methods' performance.

1) Attached is the memo contains brief description of the data and info on the workshop in general.

2) The nature (2004) paper for problem 1:
Genetic analysis of genome-wide variation in human gene expression

Another related 2005 paper:
Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease

A PLoS genetics (2005) paper:
Genome-Wide Associations of Gene Expression Variation in Humans

3) OMIM on RHEUMATOID ARTHRITIS for problem 2:
[most important papers on this disorder is linked there too]

GAW15_data_memo_FINAL.pdf

GAW 15 is around the corner

2006-02-13T19:17:00.000-05:00

To: GAW Mailing List

Plans are now underway for GAW15, to be held in St. Pete's Beach, FL from November 11-15, in conjunction with the annual IGES meeting.
At this time we are preparing data for distribution. A brief description of the dataset has been posted on the GAW website at http://www.gaworkshop.org. More details about the data will be released around 24 February.
Thank you.

Mini cluster of two computers

2006-02-13T18:24:00.000-05:00

Lei is experimenting on a mini cluster of two computers for MPI programming. Hopefully, he will rewrite all current programs in parallel so that we can enter a fast-paced era.

Group meeting(s) recap [2.3.2006]

2006-02-03T13:57:00.000-05:00

Since Professor Lo is visiting Asia and Iuliana is between her interview trips. I met with Lei and Yuejing separately today.

With Lei: we discussed next tasks on our computing needs and software developments. We will explore parallel computing options and programming needs. Another task we will be working on is to add more functions to our current BHTA and BGTA user interfaces.

With Yuejing: we discussed tasks for next week.

Group meeting recap [1.27.2006]

2006-01-27T18:58:00.000-05:00

First meeting in the new semester. Iuliana is away due to her interviews [good luck to her!]

We discussed the following items:

Return frequency reweighting
Issues specifically with classification problems
Software distribution

Panel on Grant Writing in Natural Sciences (Jan. 11. 2005)

2005-12-08T15:11:00.000-05:00

I will not be able to make it but I think it should be useful.

Graduate students in the natural sciences are invited to a panel discussion on grant writing, to be held on the Morningside campus, the week before the spring semester starts. Organized by the New York Academy of Sciences, it is open to graduate students and postdocs from around New York City, so please REGISTER SOON if you want to get a seat. http://www.nyas.org/events/browse.asp?typeID=4

Admission is FREE for members of the Science Alliance (PhD students in Astronomy, Biology, Chemistry, DEES, E3B, Physics, Psychology and the Coordinated Doctoral Program in the Basic Sciences) $10 for other students, $20 for non-students.

Wednesday, Jan 11, 2006 . 5:00 PM - 7:00 PM
Research Support for the Early Career Scientist

Speakers:
Jim Austin, Editor, Science's Next Wave
Michael Prystowsky, Chair, Council for Extramural Grants, American Cancer Society, Professor and Chairman, Department of Pathology, Albert Einstein College of Medicine
Emmeline Edwards, Deputy Director for Extramural Research, NINDS
Other speakers to be announced
Sponsored by: Science Alliance
Hear directly from our panel of grant makers and experienced grant writers on how to make the cut, avoid common mistakes and successfully apply for highly competitive research grants.

Guide to Genetic Analysis from CIGMR, U Man, UK

2005-11-07T12:58:00.000-05:00

http://slack.ser.man.ac.uk/
A nice site (under construction) from the Center of Integrated Genomic Medical Research, University of Manchester in UK.

2005-11-06T22:04:00.000-05:00

Found this nice review paper by cordell and clayton:

Genetic association studies. Cordell HJ and Clayton DG (2005) Lancet 366, 1121-1131.

There are other six review papers in this series...

Affymetrix Microarray Bulletin

2005-11-06T21:49:00.000-05:00

There is a magazine, called "Affymetrix Microarray Bulletin". It contains interviews with different scientists. The april issue has some articles on genome-wide association studies. Also there is
a special issue on HapMap. If you go to http://www.microarraybulletin.com/,
you can read, or you can subscribe to receive the issues by email.

Upcoming genetics meetings

2005-11-04T18:38:00.000-05:00

Too late to contribute:
January 3-7, 2006Computational Genetics / Bioinformatics: Call for Papers
Design & Analysis of Genetic Studies after the HapMap Project
Pacific Symposium on Biocomputing 2006, Grand Wailea Resort, Maui, Hawaii

Not too late
Annual Human Genome Meeting 2006
http://hgm2006.hugo-international.org/
May 31-June 3, 2006. Finland.

Check Hum-MolGen for more events.

GAW 15 Conference [Nov. 2006]

2005-11-04T18:32:00.000-05:00

http://www.gaworkshop.org/welcome.html

Tampa Bay, Florida. Nov 2006

We should consider attending.

Group meeting recap [11.4.2005]

2005-11-04T17:07:00.000-05:00

Iuliana just came back from the ASHG annual meeting in Salt Lake City. She briefed us on the common themes of the talks she attended: the use of HapMap results in association mapping, etc.
We discussed how to implement a normalizing component in current screening methods. Tian and Lei will discuss to have it done.
Lei showed us the latest version of the software under development. The next critical step is to refine the interface and write help documentations. Next week, Lei will give a presentation summarizing the implementation of this software.
One of our collaborators, Professor Herman Chernoff (Dept. Stat., Harvard) will be visiting us next week.