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CombiMatrix s Ali Arjomand on Developing a SARS Microarray

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At A Glance

  • Ali Arjomand, manager, business development, and senior scientist, CombiMatrix
  • 1989 — BS, genetics, University of California, Davis.
  • 1998 — PhD, nutrition, University of California, Davis.

CombiMatrix announced last week the rapid development of a microarray based on the DNA sequence of the virus linked to the outbreak of SARS (severe acute respiratory syndrome).

CombiMatrix said it fabricated microarrays within 48 hours of publication of the genetic sequence of the coronavirus, which was determined by researchers at the Centers for Disease Control in Atlanta and at the Michael Smith Genome Sciences Center in Canada. The company is offering its microarray chips at no charge to the two agencies.

BioArray News spoke with Ali Arjoman, a senior scientist for the Mulkiteo, Wash., company to learn more about its response to the global scientific challenge presented by the SARS virus.

Were you tracking SARS closely?

We were keeping up with it on a cursory level. We read in the news that it was associated with a virus, and the next step was going ahead with the sequencing. On Monday [April 14, 2003], we were surprised to see that the sequencing had been done and published by a Canadian team in Vancouver, and available through GenBank. We also found [the sequence] on the CDC database, on a PDF.

What did you do when you found the sequencing data?

We did a quick comparison of the two sequencing efforts to design a chip. We did a Blast comparison of the two and found 35 bases that were different, and then we looked into those differences and found that 15 of them were not necessarily different. The sequences were pretty much identical, one or two differences here and there, that won’t interfere with the assay itself, so it didn’t matter which sequence was used.

Why did this interest you?

It’s what our company is all about. We have worked on this for four years, developing rapid turnaround, open-ended software that can interface with any kind of data — GenBank, private databases — and ask the software to design a chip. We received an inquiry on Monday morning for a SARS microarray from a laboratory in Toronto. It took less than an hour to design after we got the sequences. The next thing we did was go to the synthesizer lab to make a batch of six chips, loading the synthesizer file we developed, and placing blank chips in the synthesizer. The whole synthesis process was about 15 hours. You just load the blank chips and the file, hit ‘go’ and walk away. You come back and open the front end and remove the chips. There is a secondary procedure, a termination step, and, at that point, they are ready for the assay. We also do a quality control, non-destructive hybridization assay on every chip.

Will you walk me through the techniques you used?

We treated this genome as a single gene and we asked the software to find unique probes, and to pick the perfect ones based on the temperature of melting.

We had the software Blast the probes against the human UniGene set to make sure there is nothing in the human genome that may interfere. Also, we asked it to reject ribosomal RNA, as a lot of times that is a contaminant. There are also six other closely associated viruses and we Blasted our probes against those to make sure that they don’t interfere as well. We wanted to increase the specificity of the chip to the SARS virus, and to eliminate the possibility that it would capture anything but SARS. The software will reject probes that have any chance of cross hybridizing. We did find 435 probes, 35- to 45-mer in length, which are unique and meet the criteria. The design is automatically laid out and we added a set of controls to help in the assay and the quality control of the chips. That was laid out geometrically to form an array, all through software. That is saved as a synthesizer file, which has the x and y positions of the spot and the sequences, for 500 different probes. They are ready to use. We are contacting people who are working in this area. We have committed to providing a limited number of microarrays at no cost. We believe they will find value.

What can your chip do?

It’s really early to know what to do with it. We can start development of screening procedures that are PCR or chip-based. There is already an effort ongoing for a quick screening test, you could do them on chips as well, the advantage being screening for this virus or five, 10, or 15 other closely related viruses that have the symptoms and present themselves with the same symptoms, you can have multiple screening assays on a chip, to differentiate one virus over the others.

The second category of applications is to look for new variants of the virus that may appear in certain locations. In that case, the microarray will be used for variant typing of samples to see if the virus is mutating.

The third area of application is for researching the fundamental biology of the virus for development of new therapies and medicines. Researchers can investigate changes in the expression of viral genes as well as changes to host pathways involved in infection. Drugs that affect expression of these genes can be screened on the same chip. There are a number of other possible applications and researchers have the flexibility to customize the content of the chip to satisfy their specific requirements.

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