[GenABEL-dev] Robust Standard Errors for Cox Proportional Hazard Regression

[Yury Aulchenko]

Dear Lennart, Alisa, all,

On Jul 25, 2012, at 10:44 AM, L.C. Karssen wrote:

> In short, the status of Cox regression in ProbABEL is the following:
> - In PA 0.2.0 Cox regression is disabled by default because it doesn't
> work correctly (but it can be enabled easily). Looking back it seems
> that it broke with the integration of the filevector/DatABEL code,
> somewhere between the 0.1-3 and 0.1-9 releases.
> - For those who want functional Cox regression (although not with
> filevector data) I suggest to use PA 0.1-3. Recently we've implemented a
> bugfix in that code base and we are almost ready to make that version
> available to the public.
> 
> So, at the moment we have two code bases. Ideally we would like to get
> the filevector problem solved in the PA 0.2.0 branch (the bugfix from
> 0.1-3 has also been implemented there). If you think you are up to it
> you are more than welcome to see if you can fix the filevector problem
> in 0.2.0!
> 
> If you want to focus more on the implementation of the weighted Cox
> regression I guess it's easier to base your work on the 0.1-3-fixes code
> where you can easily make test runs. Once it works you can forward-port
> your improvements to the 0.2.0 branch.
> 
> Yurii, do you agree?
> 

This is very good summary of where we stand now.

The big decision is whether to 

a) start with 0.2.0 and figure out why Cox does not work there (and then proceed to inclusion of robust and weighted). This may take time - we do not quite have a clue why it does not work. 

or 

b) start directly with 1.3.0-fixed (which is due to be released soon) and incorporate robust and weighted,  I think, must be relatively straightforward because actually the code is there, it is only that we do not pass right arguments and data for the code to do the job

A bit of problem with "b" is of cause that we will be getting more and more into that branch (which, because it can not use DatABEL/filevector format, is very RAM-demanding, while 0.2.0 can operate with <1Gb RAM). On the other side, if the thing which really matters is to get this functionality ASAP, and RAM is no concern, (b) is clearly the way to go. As Lennart mentioned, other possibility is to do (b) then go for (a) - though merging branches could be a nightmare.

Under any scenario you decide upon, we will be happy to help in planning and implementation (but see below).

Alisa, to make things clear from the start - do you plan to release you modifications of the code into "open", e.g. incorporate these modifications into one of the mainstream branches available for other people as part of ProbABEL releases? The reason I ask is that there are examples that people make "private" versions which they never release into open and keep for their private use. Of cause under latter scenario we have less motivation to actively help. 

> 
> On the technical side of things: do you know how to work with
> Subversion? That would make life easier, because then I could set up a
> separate branch for you to work with. So that, once your feature is
> tested and works as expected, we can easily integrate the changes in the
> main branch(es). (If all this sounds like gibberish submitting a patch
> also works :-).)
> 

Just to comment: the "normal" procedure would of cause be that people first submit a patch and then can request for commit-access to repository. On the other side, Alisa already participated in development of ProbABEL. And on the final note, the decision of granting commit-access is the decision of current active developers (meaning - for ProbABEL - Lennart, and, in lesser degree, Maarten and me). I will be happy to go along with any decision worked out by Lennart and Alisa :)

best wishes,
Yurii

-------------------------------------------------------
Yurii S. Aulchenko, PhD, Dr. Habil
Director,YuriiA consulting
Rotterdam, The Netherlands
yurii [dot] aulchenko [monkey] gmail [dot] com

> 
> Let us know what you think and if we can be of any help!
> 
> Looking forward to your contributions!
> 
> Lennart Karssen.
> 
> 
> 
> On 24/07/12 17:26, Alisa Manning wrote:
>> 
>> Hello--
>> In the past, I've been involved in code contributions to ProbABEL
>> (extracting covariance between regression estimates for snp and snp*E
>> for interaction tests).
>> 
>> I've set aside some time this summer to work on implementing a weighted
>> Cox regression model in ProbABEL -- the only change that's required in
>> the code is to implement robust standard error estimation in the cox
>> proportional hazard functionality.
>> 
>> (Aside: I see that this is a feature request)
>> 
>> I noticed that the Cox regression model is under active development in
>> ProbABEL version 0.2.0.  The purpose of this email is to check in with
>> the group regarding my plan:
>> 
>> 1) check out some latest developers version of the code
>> 2) play around with the coxph code (if it isn't fixed)
>> 3) evaluate and test in a statistical fashion (I am a biostatistician
>> after all!)
>> 4) implement robust standard error estimation
>> 5) submit patch for review 
>> 
>> Comments and ideas are welcome.
>> 
>> Thanks!
>> Alisa
>> 
>> -- 
>> 
>> Alisa Knodle Manning, Ph.D.
>> Postdoctoral Research Fellow
>> Broad Institute
>> 617-714-7662
>> amanning at broadinstitute.org <mailto:amanning at broadinstitute.org>
>> 
>> 
>> 
>> _______________________________________________
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>> genabel-devel at lists.r-forge.r-project.org
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>> 
> 
> -- 
> -----------------------------------------------
> dr. L.C. Karssen
> Erasmus MC
> Department of Epidemiology
> Room Ee-2224
> 
> Postbus 2040
> 3000 CA Rotterdam
> The Netherlands
> 
> phone: +31-10-7044217
> fax: +31-10-7044657
> e-mail: l.karssen at erasmusmc.nl
> GPG key ID: 0E1D39E3
> -----------------------------------------------
> 
> 
> 
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