From:
`Sent:
`To:
`Cc:
`Subject:
`
`Christina
`
`Stephen Quake [quake@stanford.edu]
`Monday, July 07, 2008 12:04 PM
`Yair Blumenfeld; Christina H. Fan
`Stephen Quake
`Re: latest version
`
`I am about to send you more edits. This would also be a good time to talk on the phone.
`You can call my french cell at +33 642 702902
`
`Steve
`
`Stephen Quake
`Professor of Bioengineering
`Stanford University
`
`NOTE NEW EMAIL: quake@stanford.edu
`
`-~---Original Message-----
`From: Yair Blumenfeld <yairb@stanford.edu>
`
`Date: Mon, 07 Jul 2008 10:50:23
`To: Christina H. Fan<chfan@stanford.edu>
`Cc: Stephen Quake<quake@stanford.edu>
`Subject: Re: latest version
`
`Hi Christina,
`
`I think I answered most of the comments you directed
`It looks great.
`towards me and I added a little bit about the recent ACOG Practice
`Bulletin which recommends that invasive testing now be offered to ALL
`women, regardless of risk factors.
`I think it will play nicely with
`the need for a "risk-free" non-invasive diagnostic test.
`
`Thanks,
`
`Yair
`
`Quoting "Christina H. Fan" <chfan@stanford.edu>:
`
`> hi steve, yair
`> this is the latest version of i have
`> the changes i made are:
`>
`> 1.
`> i added the references, but i couldn't find the JGI paper (not exactly
`> sure which one it is) and any relevant references for dr. snyder
`>
`> 2.
`> i added 2 or so paragraphs in the discussion
`> one of the main one is the 'problem' with our samples that they are
`> collected after amnio or CVS, according to yair. i am sure dr. bianchi
`> would raise that question if we choose not to mention it in the
`> methods because in a paper she and dennis lo wrote they made it a big
`>deal..
`·
`>
`> 3.
`> i think besides microchimerism, we should mention confined placental
`STANFORD EXHIBIT 2131
`SEQUENOM v. STANFORD
`CASE IPR2013-00390
`
`

`

`> mosacisim since it seems more relevant for the case of cell-free dna
`>since these dna potentially come from the placenta ... but i have gone
`> deep enough to be able to find references regarding how much of the
`>placenta usually has mosacisim .. yair, do you think you have any
`> references you can think of to address this issue?
`>
`> 4.
`> the graphs
`> for figure la, i changed the order of the chromosomes according to
`> there GC content as steve suggested and it looks visually much better
`>
`> for figure 2, i added the fetal DNA fraction estimated from chrX and
`> chrY ... thus figure lc is probably not neccesary .. and figure ld
`> probably isn't necessary as well (can put in supporting info)
`>
`> for figure 3b, i added the graph of cumulative fetal fraction
`>
`> 5.
`> i still dont' know what to do with the outlier point (P13)
`> it probably doesn't affect figure la and lb (it is currently included
`> in figure la and lb)
`>but when it comes to estimation of fetal DNA fraction ... the estimation
`> is based on the comparison to female pregnancies (chrX) or male donor
`>plasma (chrY) .. and in figure lc ... you can see that P13 has chrX
`>coverage even higher than female pregnancies .. which doesn't seem to
`>make sense ... currently P13 is not included in the estimation of fetal
`>dna fraction using chrX and chrY data ...
`> what should we do??
`>
`> 6.
`>one last thing that i still haven't solved ..
`> i think we need a better way of estimating the limit of our test .. the
`> use of a 95% confidence interval based on the coverage data of normal
`>pregnancies doesn't make too much sense to me after i
`thought about
`>it ... the sensitivity should somehow incorporate sampling rate (how
`>much we are sampling) which is not reflected by the 95% CI ..
`> however, due to sequencing bias, the sampling no longer follows
`>poisson distribution .. the distribution of the number of tags per 50kb
`>window deviates from normal and are skewed to the right ... i have been
`> thinking about this problem for a while and i haven't come up with a
`> solution .. perhaps steve would have a better idea??
`>
`> 7.
`> added the remaining graphs of TSS from other samples in the supporting
`> information
`>
`> i will be back in the lab at 10.30am tmr
`>
`> christina
`>
`>
`> Quoting Stephen Quake <quake@stanford.edu>:
`>
`>> ok i have done a bunch of editing and have a lot of questions (sorry
`>> to give you such a busy weekend, but it will be worth it -
`this is
`>>shaping up into a great paper!)
`>>
`>> please accept the changes i made and then track any further changes
`>> you make. let me know if you want to speak on the phone tomorrow. my
`>> usa cell works and is 626 274 5841 and it is +9 hours from you.
`>>
`>> one thing we must do is work in references to mike snyder, eddy rubin
`>> and diana bianchi since we know they are referee candidates.
`i have
`>> indicated where to do this for the last two but not for mike yet. he
`>> recently publishd something on down syndrome so it shouldn't be too
`>> tough.
`
`

`

`>>
`>> best
`>>
`>> steve
`>>
`>>
`>> -----------------------
`>> Stephen Quake
`>> Professor of Bioengineering
`>> Stanford University
`>>
`>> PLEASE REPLY TO: quake@stanford.edu
`>>
`
`Yair Blumenfeld
`Maternal-Fetal Medicine Fellow
`Department of Obstetrics & Gynecology
`Stanford University
`·
`
`