tag:blogger.com,1999:blog-36768584.post7615799363377654638..comments2024-03-03T18:49:34.382-05:00Comments on Omics! Omics!: The genomic history of a breast cancer revealedKeith Robisonhttp://www.blogger.com/profile/04765318239070312590noreply@blogger.comBlogger7125tag:blogger.com,1999:blog-36768584.post-3337020185505676222011-06-13T11:31:33.852-04:002011-06-13T11:31:33.852-04:00Funny to read this article now, it's a great a...Funny to read this article now, it's a great analysis indeed, why I called it funny you ask? well all the women in my family faced cancer and apparently it was not genetic, but since I have heard it's not genetic I really started to read more and more articles like this one.Personalized Cancer Treatmenthttp://www.personalizedcancertreatment.com/noreply@blogger.comtag:blogger.com,1999:blog-36768584.post-59761672757135344952009-10-14T15:38:29.793-04:002009-10-14T15:38:29.793-04:00Hi Keith.
I can certainly confirm that the validat...Hi Keith.<br />I can certainly confirm that the validation of our candidate variants by Sanger sequence was extremely laborious. This choice made for many headaches and late nights visually inspecting traces and I feel for the two individuals who accomplished this (Tesa and Trevor). Had we generated a whole genome sequence from the germline, we could have likely reduced this workload by an order of magnitude or more. We did, in fact, manage to produce a good library from the primary tumour sample (FFPE) but we decided not to pursue it. Considering that so few of the changes we identified in the Met sample were somatic, a genome sequence of the primary tumor would not be of much use to us. Instead, we only had to look at a few sites by PCR (and deep resequencing) to determine whether evolution had occurred. This gave us the added benefit of detecting the subclonal mutations, which we likely would have shrugged off as sequencing errors (had we seen them at all) in a 30-40X genome. I suppose you could say that we picked our battle and stuck with it. Even if in retrospect it would certainly have been better to have all 3 genomes fully sequenced, our method sufficed to tackle our rather focused questions.Unknownhttps://www.blogger.com/profile/10003146430878445396noreply@blogger.comtag:blogger.com,1999:blog-36768584.post-19046449909918974402009-10-09T21:28:00.951-04:002009-10-09T21:28:00.951-04:00Ryan:
It is always a thrill to have one of the au...Ryan:<br /><br />It is always a thrill to have one of the authors of a paper I've covered drop by for a comment!<br /><br />I did have one question for you. Before I saw your comment to moderate I was going to take a stab at Dan's comment<br />"First of all, only the metastatic sample was whole-genome sequenced - the primary tumor and matched normal were not. Instead, the authors identified nonsynonymous coding variants in met WGS data, and validated them by PCR/3730 sequencing in the met, tumor, and normal samples. This seems laborious to me, since there were 1,120 nonsynonymous SNVs..."<br /><br />I'm guessing your group picked the PCR-based deep sequencing, rather than whole genome shotgun, because the sample from the primary tumor was available only as Formalin Fixed Paraffin Embedded (FFPE) and you either had insufficient DNA for WGS or were concerned about FFPE artifacts and the need to sequence from multiple, separate DNA isolations.Keith Robisonhttps://www.blogger.com/profile/04765318239070312590noreply@blogger.comtag:blogger.com,1999:blog-36768584.post-69976599182544187122009-10-09T17:36:28.331-04:002009-10-09T17:36:28.331-04:00Hi Keith.
I'd also like to thank you for your ...Hi Keith.<br />I'd also like to thank you for your excellent and prompt summary of our paper. I am a long-time reader and was excited to find my own research featured in your blog. We are also glad you consider SNVmix to be a publishable easter egg (thus far, no editor has shared that opinion unfortunately). I'd also like to make a quick comment in our defense with regards to Dan's comment regarding our discussion of the implications of individual mutations (or rather, lack thereof) in the paper. You probably noticed that the supplement includes a more detailed discussion of the significance of the HAUS3 mutations and (to a lesser extent) PALB2, ABCB11 and SLC24A4. This was originally a section in the main text but, as is too often the case, had to be relegated to the supplement to conform to the constraints of the letter format.<br /><br />Cheers,<br /><br />RyanUnknownhttps://www.blogger.com/profile/10003146430878445396noreply@blogger.comtag:blogger.com,1999:blog-36768584.post-63710985403661893612009-10-09T16:24:09.092-04:002009-10-09T16:24:09.092-04:00Keith,
I filed a complaint with GoDaddy, the regi...Keith,<br /><br />I filed a complaint with GoDaddy, the registrar where that site appears to be hosted.<br /><br />Thanks again for the post!<br /><br />Dan Koboldt<br /><a href="http://www.massgenomics.org" rel="nofollow">MassGenomics</a>Dan Koboldthttps://www.blogger.com/profile/09836750989342667229noreply@blogger.comtag:blogger.com,1999:blog-36768584.post-5718925508292936042009-10-09T14:20:26.388-04:002009-10-09T14:20:26.388-04:00Hey, thanks for the comments (and your commentary ...Hey, thanks for the comments (and your commentary picked up some key stuff I missed!).<br /><br />The Oregon blog is wierd -- looking further I find this isn't the only piece of mine that they have lifted without attribution, including last night's post. It's almost like it is an automated plagiarism-by-RSS.Keith Robisonhttps://www.blogger.com/profile/04765318239070312590noreply@blogger.comtag:blogger.com,1999:blog-36768584.post-79620511908082094702009-10-09T13:01:51.683-04:002009-10-09T13:01:51.683-04:00Keith,
Thanks for this excellent analysis of the ...Keith,<br /><br />Thanks for this excellent analysis of the breast cancer genome paper. Your discussion of the mutated genes lends a great deal to the paper since theirs was somewhat lacking. Great job!<br /><br />Incidentally, my Google alert first picked up the text of your blog the "Oregon Personal Injury Law Blog". It looks like they stole your text and are passing it off as their own - content pirates, if you will. Let's get these guys.<br /><br />http://medicalcenterinfo.com/2009/10/07/the-genomic-history-of-a-breast-cancer-revealed/Dan Koboldthttps://www.blogger.com/profile/09836750989342667229noreply@blogger.com