FUNCTIONAL GENOMICS

 

 

IPAM  Fall 2000

 

 

Organizing Committee

Kenneth Lange, Simon Tavaré, Michael Waterman, Wing Wong

 

Program period: Sept. 18-Dec 15, 2000


Sept. 18

Orientation

Sept. 19-27

Tutorials

Oct. 11-15

Expression Array Technologies and Methods of Analysis

Nov. 8-12

Expression Arrays, Genetic Networks and Diseases

Dec. 11-15

Mathematical and Statistical Challenges from Computational Biology

 

This program will take place at the Institute for Pure and Applied Mathematics (IPAM), a new NSF national mathematical sciences research institute located on the UCLA campus.  Mathematicians, statisticians, computer scientists, and biologists—from academia and from industry—are all invited to attend.

 

Funding for participants at all levels is available, but especially for graduate students and recent PhD’s.  Applications to attend the full program are available at www.ipam.ucla.edu . 

 

Program Activities:

 

Seminar Series I

·         Biological problems, experimental approaches and new technology.

·         Speakers to be drawn from participating biologists and scientists from various academic and industry laboratories.

·         To be run by senior participants. Weekly.

 

Seminar Series II

·         Mathematical, statistical and computational problems in functional genomics and expression array analysis.

·         To be run by senior participants. Weekly.

 

Seminar Series III:  Postdoc Seminars. Weekly.

 

Journal Club: Run by postdocs

 

Brainstorming Seminar

·         Organized by UCLA Bioinformatics Institute—Chris Lee

 

Statistical Genetics Course

·         Biomath 207A, by Ken Lange. Open to IPAM participants.

 

High Dimensional Data Sets Course

·         Statistics 216, by Ker-Chau Li.  Open to IPAM participants.

 

 

Special Events:

 

Orientation

·         September 18, Monday

·         At May’s Landing, Malibu

 

Tutorials:

·         September 19-27

·         Terry Speed: “Overview of Computational Biology for Mathematical Scientists” (9-10 lectures)

·         Gary Churchill: “Experimental Design and Data Analysis for Gene Expression Microarrays" (3 lectures)

·         Tim Triche, "Gene Expression Profiling as Indices of Biologic and Clinical Behavior in Cancer: Comparison of Clustering Methods and Correlative Biologic Indicators" (3 lectures)

·         Chris Lee, TBA

·         Roger Brent, TBA

 

Workshop on “Expression Array Technologies and Methods of Analysis” (October 11-15).

·         Organizing committee: Fred Fox (UCLA), Mel Kronick (Agilent), Michael Waterman (USC).

·         Discussion of current and future technology for gene expression monitoring

·         Methods for analysis of information generated by such technologies.

·         Representatives from major companies in this area e.g. Affymetrix, Incyte, Agilent, Rosetta, Illumina, Gene Logic, etc

 

Workshop on “Expression arrays, Genetic Networks and Diseases” (November 8-12).

·         Organizing committee: Rich Simon (NCI), Simon Tavaré (USC), Terry Speed (Berkeley).

·         Application of expression arrays to the study and diagnosis of major diseases such as cancer and allergy

·         Complex gene regulation network in the cell.

 

Meeting on “Mathematical and Statistical Challenges from Computational Biology” (December 11-15).

·         Organizers: Peter Bickel (Berkeley), Ken Lange (UCLA), Wing Wong (UCLA).

·         To be held in the UCLA Conference Center in Lake Arrowhead.

 

 

 

Scientific Content of the Program:

 

The genes of all cells are composed of DNA. Proteins serve as structural components as well as enzymes within cells but the genes contain the blueprints for each protein and the program for controlling the production of proteins. Genes are transcribed to produce complementary molecules of mRNA (messenger RNA) and the mRNA is translated to proteins. There is a one to one correspondence (almost) between genes and proteins. Proteins perform the work of cells such as energy production, reaction catalysis, inter-cellular signaling, transcription and translation, cell reproduction, etc. All cells of an organism contain the same DNA. The level of production of the each of the types of proteins specifies the state of a cell. This state is determined by spatial and temporal variables such as tissue location and extra-cellular stimuli. Level of production of a

protein is determined primarily by level of transcription of the corresponding gene into mRNA.

 

With the recent development of gene expression arrays, it has become possible to simultaneously measure the level of expression of thousands of genes by measuring the amount of each type of mRNA present in a collection of cells. This is done by printing DNA samples at high density onto a microscope slide to create a DNA microarray that can be used, through hybridization, to probe a complex mixture of RNA or cDNA molecules derived from a particular cell source. Alternatively, oligonucleotide probes for the mRNA or cDNA molecules can be directly synthesized at very high density onto microchips by photo-litography or ink-jet technology.  Biologists will study differences in gene expression among cell types to elucidate the steps of normal development and tissue differentiation. By examining the level of gene expression in cell populations of disease and pre-disease states, investigators will attempt to understand the steps of disease development and to identify the genes involved in disease susceptibility and gene-environment interactions. Currently DNA microarrays contain 10,000-20,000 of the complement of approximately 75,000 human genes. Within the next 2 years it is anticipated that microarrays will be produced that contain DNA from almost all human genes.

 

The greatest hurdles to the effective development and use of DNA microarrays are problems of mathematics and statistics. There are key problems of image analysis of the fluorescent signals for which improved solutions are needed. There are difficult problems of combinatorial mathematics for the design of oligonucleotides in the related development of oligo-arrays that are

useful for new sequencing and genotyping methods. There are challenging problems of how to elucidate genetic networks based on time-sequenced gene expression data. There are important problems of how to classify cells based on expression pattern and how to develop diagnostic disease classifications systems. Because of the high dimensionality of the data obtained from microarray experiments, there are many challenging problems of multiplicity and multivariate analysis that must be addressed. DNA microarrays will finally provide the data to attempt to understand simple organisms as entire systems and this will require new levels of collaboration among mathematical scientists and biologists.

 

The goal of this program is to bring leading investigators in this area into contact with other mathematicians and statisticians, especially those of the younger generation, who are interested in participating in these interdisciplinary research areas. Such a program will serve the timely and important function of disseminating the current scientific issues to the wider mathematical community. It will also provide an opportunity for active researchers to interact closely and intensely. As is often the case in emerging fields, although it is clear that mathematics will play a central role in the future progress of these areas, the mathematical formulations have not been sufficiently developed. A major goal of the program is to help to identify and crystallize the formulation of the mathematical, statistical and computational issues, and to form a working group of interdisciplinary researchers.

 

Partial list of scientists who have agreed to participate and spend

significant time (from 7 days to 3 months) at the Institute:

 

Gary Churchill, Jackson Laboratory

Jean-Michel Claverie, IGS, Marseilles

David Haussler, U.C. Santa Cruz

Mel Kronick, Agilent Technologies

Kenneth Lange, U.C. Los Angeles (co-organizer)

Bud Mishra, Courant Institute

Pete Smietana, GeneLogic

Richard Simon, National Institute of Health.

Terry Speed, U.C. Berkeley and Hall Institute of Medical Research, Melbourne

Simon Tavaré, University of Southern California (co-organizer).

Michael Waterman, University of Southern California (co-organizer).

Wing Hung Wong, U.C. Los Angeles (co-organizer).

(Additional senior participants will be invited)

 

In addition, there will be short term visitors including representatives

from various academic experimental groups, and from related biotechnology

companies such as Roche Bioscience, Affymetrix, Agilent and Rosetta.

 

Funding:

Substantial funding is available, especially for advanced graduate students and post-docs, for those who want to attend the full program.  Please contact us if you are interested or get an application via the IPAM website.

 

Contact:

Institute for Pure and Applied Mathematics (IPAM)

e-mail: ipam@ucla.edu

web: www.ipam.ucla.edu