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BioArray Q&A: Affymetrix s Alicia Burt Discusses the Firm s ENCODE Array

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A few days ago, Affymetrix announced the launch of a new GeneChip microarray that is being used in the Encyclopedia of Complete DNA Elements (ENCODE) initiative, a project funded by the National Human Genome Research Institute with the goal of creating a “parts list” of all the sequence-based functional elements in the human DNA sequence. The launch of the ENCODE “tiling” array coincides with a new round of grants announced last week by NHGRI to support the next phase of research on the project. (see BioArray Briefs, p. 8)

Alicia Burt, a senior product manager for expression marketing at Affymetrix, explained the content of the chip and Affy’s involvement in the program in an e-mail interview conducted this week by BioArray News.

What is the content of the ENCODE chip?

The GeneChip ENCODE01 array contains millions of DNA probes evenly spaced, or tiled, across 35 million base pairs of DNA specifically chosen as a representative sampling of the complete genome sequence.

These regions of DNA were selected by a committee of the National Human Genome Research Institute and will serve as a pilot for further microarray-based ENCODE research. Half of the content on the array was manually selected by the NHGRI committee, while the remaining 50 percent was randomly selected. The manually selected regions were chosen based on the presence of well-studied genes or other known sequence elements, and the existence of a substantial amount of comparative sequence data. A total of 14.82 Mb of sequence was manually selected and include 14 targets ranging in size from 500 kb to 2 Mb. To ensure good sampling of genomic regions varying widely in their content of genes and other functional elements, the randomly selected content includes thirty 500 kb regions selected based on gene density and level of non-exonic conservation. Content for the array was run against RepeatMasker and only non-repetitive sequences were included.

Has Affy been participating in this project under a contract, or did the firm get the content from a public database and develop the array based on that?

The transcriptome research group at Affymetrix, led by Thomas Gingeras, actively participates in the ENCODE consortium and is supported, in part, by a grant from NHGRI. Additionally, the ENCODE pilot DNA regions are posted by the UCSC genome browser at the following site: http://genome.ucsc.edu/ENCODE/regions.html.

Has the firm been involved with the ENCODE project since its launch in Sep. 2003?

Yes. Thomas Gingeras participated in the initial NHGRI workshop to initiate the ENCODE project.

Is Affy the only microarray manufacturer making these tiling arrays for the project?

Affymetrix is one of two microarray companies participating in the ENCODE consortium. NimbleGen Systems offers microarray processing services and also participates in the ENCODE consortium.

How are these arrays different from what Affymetrix has been offering?

The ENCODE01 Array is among the first wave of tiling array products from Affymetrix. Tiling arrays are an evolution of expression microarrays and offer researchers a more detailed view of the genome. Previously, expression arrays have been designed using annotations in public databases to focus specifically on expressed regions of DNA. Tiling arrays are a new concept in microarrays and have been made possible by increased resolution in array manufacturing and imaging processes. Tiling arrays have been designed to include all DNA regions, including intergenic or “junk DNA,” in addition to putatively expressed regions.

In an industry first, tiling arrays provide scientists with the only single tool available for genome-wide analyses of many important biological functions. While tiling arrays give a more detailed view of genome-wide transcription than ever before, they also allow researchers to analyze other aspects of genome function, including transcription factor binding sites, sites of chromatin modification, sites of DNA methylation, and even chromosomal origins of replication.

Do the tiling arrays run on the standard GeneChip platform?

Yes. The ENCODE01 Array is compatible with the Affymetrix instrumentation including the GeneChip Scanner 3000, Hybridization Oven, and Fluidics Station. Researchers in the Affymetrix early access program are developing new sample preparation methods and data analysis techniques specifically for the tiling arrays.

How much do the arrays cost?

The cost varies based on the number of arrays ordered.

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