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Human Genome News Archive Edition

Human Genome News, July 1990; 2(2)

Electrophoresis, Supercomputing, and the Human Genome

The First International Conference on Electrophoresis, Supercomputing, and the Human Genome was held April 10-13 in Tallahassee, Florida. Hosted by the Supercomputer Computations Research Institute (SCRI) of Florida State University, the meeting attracted about 110 international participants, including representatives from France, Japan, Sweden, the United Kingdom, the United States, the U.S.S.R., and Yugoslavia. The interdisciplinary conference was planned to foster the exchange of ideas and information regarding improvement of technology and involved computational experts, experimentalists, and technologists.

Since the start of the genome initiative, the necessary involvement of scientists with widely divergent backgrounds has been evident. The correct handling, analysis interpretation, and dissemination of data and information and the control and data gathering of automated processes are areas where computer science is directly involved. Possibly not so obvious, but of increasing importance, is the use of computers to model complex phenomena such as pulsed-field gel (PFG) electrophoretic parameters during DNA fragment separation. The desire to understand provided common ground for scientists from all disciplines at this meeting. Program highlights are given below.

Computing Applications
George I. Bell [Los Alamos National Laboratory (LANL)] opened the meeting with an excellent overview of the involvement of computers in the Human Genome Project, emphasizing computerization of overlap probabilities for contig assembly, sequence similarity comparisons, and identification of intron-exon boundaries.

Tom Duke (TCM/Cavendish Laboratory, U.K.), Bengt Norden (Chalmers Institute of Technology, Sweden), Jean Louis Viovy (CNRS Laboratorie de Physiochimie Theoretique, France), J. M. Duestch (University of California at Santa Cruz), and Y. P. Papov (U.S.S.R. Academy of Science) made presentations on theoretical modeling and computer simulations of the serpentine movement of DNA during PFG electrophoresis. Nancy Stellwagen (University of Iowa) described her experimental results on orientation effects of electric fields on agarose gels. Electric birefringence studies of gels and preliminary studies with DNA indicate that DNA migration can be influenced by orientation and reorientation of the gel matrix by the electric field.

Anthony V. Carrano (Lawrence Livermore National Laboratory) described automation and computerization currently being used to construct physical maps. A unique set of computer programs, a database management system, and a workstation computer network complement automatic contig mapping using restriction enzymes. Over 4000 cosmids have been assembled into about 400 contigs for chromosome 19.

In the realm of supercomputers, William Shoaff (Florida Institute of Technology) presented his work on building a supercomputer model of a human chromosome. Parallel computer architecture was not neglected at this conference; Robert Jones (Thinking Machines, Inc.) reported his work on multiple sequence alignment using a massively parallel machine.

Laboratory Applications
Many interesting papers were presented on gel electrophoresis. Using a modified electrophoresis system with high voltages and efficient cooling, Eric Fairfield (LANL) achieved separation by agarose gel electrophoresis of fragments up to 4 kb in length in very short running times.

An experimental highlight presented by Levy Ulanovsky (Harvard University Biolabs) described a new technique for binding a bulky protein (streptavidin) to the end of single-stranded DNA; modifying DNA in this way facilitates separation of larger single strands on polyacrylamide gels. Applied to DNA sequencing, this technology promises to help raise the 250- to 300-bp upper limit on resolution caused by the inability to resolve large single-stranded fragments on polyacrylamide gels.

Y. P. Lysov (Engelhardt Institute of Molecular Biology, U.S.S.R.) presented a general overview of random oligo hybridization sequencing. R. Drmanac (Imperial Cancer Research Fund, London) reported on developing a miniaturized "sequencing chip" for rapid hybridization and readout using image processing and on experimental work using 6- to 8-mer probes of a human fetal brain cDNA library on nylon membranes. Both speakers emphasized the importance of computers for interpretation and quantification of sequencing-by-hybridization (SBH) results.

Other presentations ranged from in-gel DNA reassociation by Michio Oishi (University of Tokyo) and computer analysis of protein structure by Y. V. Sergeev (U.S.S.R. Academy of Science) to an informative overview of GenBank® by Paul Gilna (LANL).

Overviews and Conclusions
Evening sessions included informative overviews of their respective country's genome effort by Alexander A. Bayev (U.S.S.R. Academy of Science), Charles R. Cantor (Lawrence Berkeley Laboratory) and Charles DeLisi (Boston University), and Nobuyoshi Shimizu (Keio University School of Medicine, Japan).

Conclusions from the conference include the following:

  • The DOE-NIH 5-Year Plan is achievable. Improvements in technologies and instrumentation are necessary.
  • Computers will become more important to the project because they are needed for a number of applications, including:
    • genome workstations for accessing a series of databases and for manipulating and updating data to accomplish gene sequence analysis;
    • supercomputers for simulating protein structure and function, for molecular recognition, and for determining macromolecular folding; and
    • automated programmable machines for the sequencing process.
  • Animal models are needed to correlate with human genome data.

Conference proceedings (ISBN: 981-02-0273-3) will be published by World Scientific Publishing Co., Ltd., (201) 837-8858, and will be available in December.

Reported by Richard J. Douthart, Life Sciences Center, Battelle Pacific Northwest Laboratories
and Hwa A. Lim, SCRI, Florida State University

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Human Genome Program, U.S. Department of Energy, Human Genome News (v2n2).

Human Genome Project 1990–2003

The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.

Human Genome News

Published from 1989 until 2002, this newsletter facilitated HGP communication, helped prevent duplication of research effort, and informed persons interested in genome research.