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Mouse Researchers Outline Informatics Needs; Public EST Encyclopedia Finalized

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PRINCETON, NJ--Development of transportable software tools was highlighted as a top priority for the mouse genome sequencing community during a meeting of mouse genetics, sequencing, and bioinformatics specialists here last month. In a report, Janan Eppig, a bioinformatics expert from the Jackson Laboratory, the meeting's sponsor, indicated that inadequate informatics is a primary concern among US and European researchers who met on the Princeton University campus to establish priorities and approaches for a mouse sequencing initiative.

The meeting here followed a recent announcement by the US National Institutes of Health, which said it intends to support establishment of several new mouse sequencing centers with a goal to obtain five-times coverage of the genome by 2003. Researchers view the mouse sequence as a critical tool for understanding the human genome, especially, Eppig reported, for determining intron and extron structure, identifying noncoding functional elements such as control regions, and acquiring an understanding of evolutionary mechanisms. But several scientists at the meeting warned that the community must develop an action plan for informatics to support a scaled-up sequencing effort.

Lee Hood of the University of Washington reportedly told the group that analysis of chromosome function genes, expressed sequence tags (ESTs), and cDNAs is best tackled by comparative analysis of mouse and human sequences. But, he added, a major effort must be made to develop effective software programs that can assemble syntenic regions in multiple species with minimum error and search for relationships in noncontiguous sequences. Web Miller of Penn-sylvania State University suggested bringing software developers together with mouse sequence researchers to determine the community's software needs.

Elbert Branscomb of the Joint Genome Institute contended that another major prob-lem for new mouse seqencing centers is achieving the critical mass required to support an adequate informatics program. To be cost-effective and to complete the mouse sequence by the goal date, Branscomb said new centers must reach 2 million lanes per year. For small facilities, scaling up to that capacity also poses quality-control challenges, he asserted.

Gerry Rubin of the University of California, Berkeley, whose sequencing operation achieves 400,00 lanes per year, suggested that transferring technology among production facilities can cut costs and save time. Established centers should share informatics tools with new facilities to help them avoid spending time developing their own software and repeating mistakes made elsewhere, he said. Rubin also suggested that new centers partner with one another or establish satellite relationships with existing centers to utilize existing software.

Mouse EST encyclopedia

In other mouse genomics news last month, the availability of an encyclopedia containing 93 percent of all publicly available mouse ESTs was announced. A collaborative project among scientists at the Howard Hughes Medical Institute, the Washingon University Genome Sequencing Center, the University of Iowa, the Oklahoma Medical Research Foundation, and Lawrence Livermore National Laboratory produced a catalog of 360,000 mouse gene fragments. The free, publicly accessible database is available at http://www.hhmi.org.

The data, some of which have been available to researchers since early 1996, have been released over the internet as they have been generated over the past three years. In an article in Nature Genetics this month, researchers described how they generated the large database. A team at Washington Unversity sequenced and analyzed gene fragments and submitted ESTs to public databases. Their colleagues in Iowa and Oklahoma created libraries of messenger RNA clones that were used for sequencing. Finally, Lawrence Livermore researchers distributed them.

Now that the database is well stocked, the Washington University group is trying to determine just how many of the estimated 100,000 mouse genes are represented among the 360,000 ESTs they have catalogued.

--Adrienne Burke

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