To: scaram(o)uche who wrote (4105 ) 3/16/2006 3:20:37 PM From: dr.praveen Read Replies (3) | Respond to of 12215 Solexa/Hi Rick n Board, This was my orignal post reg SLXA These are my brief thoughts why I think Solexa is better than CRGN General: I personally feel Solexa will be able to sequence a mammalian genome for $100,000 or less in 2006.Their 1G Analyzer can sequence 1 billion bases in one to two days.It's called Genome Sequencer 1G — the 1G stands for one billion, because they think each flow cell can read 1 billion raw bases of DNA sequence. Solexa is not only gene sequencing & personalized medicine, but it is also gene expression, and gene expression is expected to be a very big market. Solexa expects being able to do one billion bases per run by the end of this year as compared to 454 20 million bases per run. So it will be more economical and have high through output than 454. Solexa unlike 454, is a pure-play company and you don't need to pay for 454 drug pipeline. Specific Adv: 454 uses pyrosequencing,while Solexa uses reversible terminators and specially engineered reagents and enzymes. In pyrosequencing, you put one base into the mixture at a time.Solexa puts all four bases at once, so the polymerase enzyme has the chance to decide which is the correct base. So you get a higher accuracy, because the enzyme always has the right choice to make. 454's technology produces average read lengths of 100 bases, Solexa is currently at the 25-read-length mark. But they have calculated that such read lengths are sufficient to assemble 80 percent of the human genome. Solexa is doing refinements to increase individual fragment lengths, they think they won't have a substantial impact on the assembly efficiency. Solexa thinks they more than compensate for that by using much smaller beads, producing a roughly 1,000-fold increase in bead density compared to 454. Solexa has done a detailed bioinformatics analysis of how long a read needed to find that unique position that read. One has to position the read with some sequence differences. From that point of view, Solexa thinks longer is better up to a point, but as read length increases,it reaches a plateau around about 80 percent of the genome is resequenceable between 25-30 bases. If one goes to 40 or 50 bases, they only gain a small percentage.So from that angle, it's better to have a very large number of short reads. Solexa thinks that Hapmap is the future and of capturing potentially all the variation rather than just sampling parts of it, they think it is the future of Solexa. I personally feel Solexa is better than 454, but it might not be the future. 5-10 years from now there might be a new co which does nanopore sequencing which might be the future. But Solexa looks interesting at the current prices... Dr.Praveen