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ZS Genetics Preps for Long-Read Sequences

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ZS Genetics is hoping to leverage recent technical developments it has made to sequence DNA later this year, using its transmission electron microscopy-based single-molecule technology.

The North Reading, Mass.-based startup hopes that read lengths of several kilobases, coupled with a throughput similar to current second-generation sequencing platforms, will persuade potential customers to go with its technology, which will require buying a pricey piece of equipment but promises very low running costs.

"One of the overwhelming selling points of the ZS approach is going to be sequence length," says Kelley Thomas, co-director of the Hubbard Center for Genome Studies at the University of New Hampshire and a ZS Genetics collaborator and scientific advisory board member. "It's an inherent property of the approach that allows the sequences, potentially, to be captured in very long stretches."

Since it was founded in 2005, ZS Genetics has been developing a method that uses a transmission electron microscope to directly image double-stranded DNA molecules. Since DNA is normally invisible to TEM because of poor contrast, the company generates DNA where most of the bases contain heavy atoms. These bases appear in the electron micrograph as black dots of different sizes, depending on the label.

The labeled nucleotides are incorporated in an in vitro synthesis reaction using undisclosed polymerases. The plan is to use three different labels initially and leave one base unlabeled, according to president and founder William Glover. He and his colleagues have already prepared DNA with three labels but have not yet sequenced it.

The length of the modified template DNA will determine the read length of the system. Based on their initial results, Glover said he is confident that the company will be able to reach a read length of 5 to 8 kilobases, though he would like to extend this to 10 to 12 kilobases.

Julia Karow

Sequencing Notes

Pacific Biosciences acquired Li-Cor Biosciences' single-molecule sequencing technology. The tool identifies nucleotides in a DNA sequence based upon synthesis of a complementary DNA strand. Pacific Bio acquired a number of patents covering the technology.

Two research teams independently published the first peer-reviewed studies involving Applied Biosystems' SOLiD technology. In Genome Research, Stanford's Andrew Fire and colleagues report using the SOLiD to generate a high-resolution map of putative nucleosome cores in C. elegans. The other study, in Nature Methods, from Sean Grimmond at the University of Queensland, used it to profile the transcriptomes of undifferentiated mouse embryonic stem cells and embryoid bodies.

Datapoint

150
The USDA released sequences of 150 different avian influenza viruses and will make the data available in GenBank.

Funded Grants

$216,691/FY2007
Pair-end-ditag technologies for the complete annotation of fusion genes
Grantee: Edison Liu, Genome Institute of Singapore
Began: Sep. 13, 2007; Ends: Aug 30, 2010

Liu's team has developed a tool, Gene Identification Signature Pair-end-diTag, which captures and joins the 5' and 3' ends of most 18-base pair clone inserts. When coupled with advanced sequencing technologies, the technology should annotate an entire transcriptome 300-500 fold faster and less expensively than contemporary cloning and sequencing. In this project, the team will use the tool to study primary breast cancers.

$347,917/FY2007
High-definition in vivo footprinting via single molecule sequencing
Grantee: Michael Dorschner, University of Washington
Began: Aug. 10, 2007; Ends: Jun. 30, 2010

This group says it plans to develop a high-throughput, high-resolution in vivo footprinting method based on next-generation, single-molecule DNA sequencing technology. They aim to modify standard ligation-mediated PCR to create a tool that ascertains the sequence of protein binding sites by sequencing short cleavage signature tags and counting how often a tag terminates at each nucleotide position within a designated area.