To: Biotech Jim who wrote (783 ) 12/5/1998 1:58:00 PM From: Rocketman Respond to of 3202
Re: GenScope <"The technology generates a single DNA fragment from each gene in an amount reflective of the gene's level of expression."> That sentence caught my eye too. When INCY does their sequencing, (at least in the old days circa a few years ago, but it wouldn't surprise me if they have found a way to be more efficient, they certainly were looking for them) since it is mRNA based, genes that are in high copy level give you a lot of copies that end up being sequenced. Genes that are in low copy level don't, and thus are harder to find. What you are essentially getting is a snapshot in time of what that particular tissue was expressing at that point in time. Out of say 5000 sequences run, you might have sequenced 100 copies of a gene that is common in that cell, but only 1 of something rare. By comparing various states of the same tissue, for example cancerous versus normal, you can get an idea of what has changed, in the cancerous a previously non-existent or low copy number gene may now be present in abundance. This gives a huge amount of information about the tissue and clues to what is happening that makes it different. But, it also makes it hard to find genes that are rarely expressed, or expressed only in a very low number, and thus makes genome closure (finding every gene) pretty difficult to not only accomplish, but also for you to be certain that you have accomplished. From PKN: <<<<<<< And because a high percentage of our GeneTag database represents coding sequence, we can just as quickly provide putative functions for those genes.'' The GeneTag process used to develop the rat gene database is a versatile technology that has been applied to global gene expression profiling and gene discovery. It is also an extremely efficient means of generating gene sequence databases for virtually any species. PE GenScope is using the technology to develop custom GeneTag databases of additional tissues and animal models critical to pharmaceutical research. The technology generates a single DNA fragment from each gene in an amount reflective of the gene's level of expression. By measuring expression levels of all RNA transcripts (known and unknown) that are present in a cell or tissue, GeneTag technology enables researchers to monitor known genes while discovering novel ones, and plays a vital role in molecular toxicology, gene discovery, and pharmacogenomics. More importantly, the technology also provides information specific to the particular biological pathway, disease model or drug response under investigation. This capability accelerates the gene discovery process and is more expedient than alternative methods, such as expressed-sequence tags (ESTs) or chip-based methods. >>>>>>>> My impression is that they are able to somehow pick out the common expressed genes by tagging them, giving some idea of expression of these, and then sequence the untagged unknowns including the non-coding non-gene areas to discover the hard to find genes. But this is really just a guess. From a pure discovery every gene standpoint you can read all the junk too, using the whole genome shotgun approach. But, you just don't get the expression (snapshot in time) information this way. This expression profile is really useful in finding targets because it allows you to see how a cell is changing. From a discover every last gene standpoint the whole genome shotgun approach should allow closure, but doesn't really tell you when and how much each gene is expressed in a given tissue that is at a specific physiological state. There is value in each method. Let me know what you find out about this stuff.