tag:blogger.com,1999:blog-36768584.post5963844902878240798..comments2024-03-03T18:49:34.382-05:00Comments on Omics! Omics!: Roche Taps PacBio for Human DiagnosticsKeith Robisonhttp://www.blogger.com/profile/04765318239070312590noreply@blogger.comBlogger7125tag:blogger.com,1999:blog-36768584.post-1978373591945619732013-11-21T07:25:07.946-05:002013-11-21T07:25:07.946-05:00Hi Keith,
FraX is a good example. CGG-Repeat. Plu...Hi Keith,<br /><br />FraX is a good example. CGG-Repeat. Plus, there you have the methylation, as there are (rare) males with full repeat expansion (more than 200 Repeats, often 800 and more) and still no methylation of the expanded allel (high functioning expanded males). And while most PCR protocolls these days are very good at amplifying these repeats, there is always this remaining little bit of nagging doubt especially in females homozygous for a normal allel, which is why some old-school clinical geneticists would still consider the good old Ed Southern J Mol Bio 1975 as gold standard in that case.....<br /><br />And as to methylation in clinical diagnostics: You missed more than a decade of imprinting diseases! Angelman Syndrome, Prader-Willi Syndrome, Beckwith-Wiedemann Syndrome, Silver-Russel Syndrome etc. However, with methylation specific MLPA, these are easily and cheaply diagnosed, so not quite sure if that helps much for a 800k machine..... <br /><br />More commercially interesting might be promoter methylation in somatic cancer analysis. If you have a system that gives you mutations and promoter hypermethylation in one run, that might be a very big advantage over any other current system.<br /><br />Alway enjoy reading your blog here in Germany. <br /><br />LarsAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-82731974567327011132013-10-18T17:45:49.748-04:002013-10-18T17:45:49.748-04:00It sounds to me like repeat diseases such as fragi...It sounds to me like repeat diseases such as fragile X are likely to be in their sights.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-54908965779291379772013-09-29T19:25:05.681-04:002013-09-29T19:25:05.681-04:00PacBo has been developing a smaller version of the...PacBo has been developing a smaller version of the RS for some time. I wonder if that one will be used in this case...Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36768584.post-24594218788682331312013-09-28T23:16:15.620-04:002013-09-28T23:16:15.620-04:00The paper using amplicon sequencing on the PacBio ...The paper using amplicon sequencing on the PacBio system has published: <a href="http://www.atsjournals.org/doi/abs/10.1165/rcmb.2013-0235OC#.UkeZ84asiM5" rel="nofollow">Genome Reference and Sequence Variation in the Large Repetitive Central Exon of Human MUC5AC</a>Keith Robisonhttps://www.blogger.com/profile/04765318239070312590noreply@blogger.comtag:blogger.com,1999:blog-36768584.post-24274165761010962112013-09-27T08:43:15.351-04:002013-09-27T08:43:15.351-04:00PacBio / their collaborators had a poster at AGBT1...PacBio / their collaborators had a poster at AGBT13 showing the ability to read a long VNTR in a mucin gene, a VNTR that turns out to be polymorphic and one of the alleles leads to a disease state. It may have been related to <a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0025452" rel="nofollow">this PLoS One paper</a><br /><br />PacBio has no PCR, so the opportunities for mischief such as slippage are reduced. Perhaps more importantly, any error should be independent, whereas a slippage event early in PCR leads to a jackpot. <br /><br />If the VNTR is longer than the read length of a given technology, then you just can't measure it (though certainly careful calibration of PacBio would be in order using some known standards); this will make Moleculo less valuable for this application.<br />Keith Robisonhttps://www.blogger.com/profile/04765318239070312590noreply@blogger.comtag:blogger.com,1999:blog-36768584.post-6507597058996058062013-09-27T08:15:24.729-04:002013-09-27T08:15:24.729-04:00Thank you for another fascinating article. I was w...Thank you for another fascinating article. I was wondering about your statement about PacBio's systems improved ability at "Sequencing through nasty simple repeats to pull out disease alleles". My understanding is that the majority of issues with sequencing short repeats, such as dinucleotide microsatellites, is strand slippage as a result of polymerase infidelity. Could you comment on why the PacBio system would be better at combatting this problem?Anonymoushttps://www.blogger.com/profile/03662812532878878928noreply@blogger.comtag:blogger.com,1999:blog-36768584.post-54018834386548827122013-09-26T21:07:55.641-04:002013-09-26T21:07:55.641-04:00Haha yeah I was going to comment on the extreme in...Haha yeah I was going to comment on the extreme inflation of the RS machine price!<br /><br />I have to believe that Roche has something in mind regarding applying the deal towards oncology clinical trial use and/or development of companion diagnostics for targeted cancer therapies.<br /><br />Since PACB had long been stating that the future of their business model depended on the clinical market, once cannot lament the losses around the edges for research applications too much. As you said, this deal is a major lifeline providing an alternative to bankruptcy or a GNOM-like takeout.<br /><br />Based on the GNOM buyout filings, I think Roche was one of the companies kicking the tires and looking to do some sort of deal with them first. And of course they had interest in ILMN too. Maybe they don't care so much which tenchology to partner with!BioDueDiligencehttp://www.biotechduediligence.com/gnom.htmlnoreply@blogger.com