Sequencing by oligonucleotide hybridization: a promising framework in decoding of the genome program?

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A very fast highly parallel microsequencing process on the megabase scale followed by sophisticated computation will be a basic technology for research on the genome level. Sequencing by oligonucleotide hybridization has the theoretical potential for a genome sequencing technique. The positions of 4 nucleotides are determined from the oligonucleotide contents of clones by a computational deduction. The sequence is generated, instead of read. The high efficiency of this method is based on simple experimental data and intensive computing. We have already developed a discriminative hybridization with oligonucleotides as short as 6-mers (successfully determining 100 bp of known sequence), an algorithm for sequence generation which tolerates as much as 20% false positive and false negative oligonucleotides, and a concept of the "sequencing chip" with a potential for substantial miniaturization and a sequencing speed of over 10 million bp per day. The informatical (computational) work has to assume a main role in an efficient analysis of both primary structure and biological functions of the different components of the genome program. In addition, it is very important to start modeling of the genome program. The prediction of biological roles of specific functional units of the genome would replace some complex experimental research.

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会议时间:

1991

被引量:

193

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2002
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