[bip] [acameron at caltech.edu: RE: online sites for doing binding site search]

Titus Brown titus at caltech.edu
Fri Nov 30 16:54:18 PST 2007


----- Forwarded message from Andrew Cameron <acameron at caltech.edu> -----

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From: Andrew Cameron <acameron at caltech.edu>
To: titus at idyll.org
Subject: RE: [bip] online sites for doing binding site search

HI, All:

Here it is late Friday afternoon and a good time to ramble on about
regulatory module search tools.  It's been 40 some years since Nirenberg and
Singer worked out the genetic code for proteins and, I think, only 10+ since
computational predictions of protein coding sequence have worked well.  So
maybe it's too early to expect good methods for finding regulatory regions.

It's pretty obvious that the complexity of transcription factor binding
sites is greater than amino acid codons.  And that the general rules are
more complicated too.  But maybe the Nirenberg/Singer approach is one to
consider.  They made synthetic mRNAs and translated them in cell-free
systems. Could be (is being) done with RNA polymerase in a cell free system,
too. I wonder how many combinations of what length would need to be tested?

On a more practical plane I agree with both Titus and Erich.  I've used
JASPAR and Cluster-buster to search but I haven't been satisfied with the
results.  It's been difficult to design Cluster-buster parameters to find
known well characterized modules.  The known ones are usually embedded in a
forest of false positives, probably due to the laxity of the PWMs used.

Have a good weekend

ANDY

-----Original Message-----
From: biology-in-python-bounces at lists.idyll.org
[mailto:biology-in-python-bounces at lists.idyll.org] On Behalf Of Titus Brown
Sent: Friday, November 30, 2007 2:23 PM
To: Erich Schwarz
Cc: bip at lists.idyll.org
Subject: Re: [bip] online sites for doing binding site search

On Fri, Nov 30, 2007 at 01:02:27PM -0800, Erich Schwarz wrote:
-> On Thu, 29 Nov 2007, Titus Brown wrote:
-> 
-> > ...  I'm writing a short review/HOWTO on finding cis-regulatory
-> > elements in chick ...
-> 
->     My own jaundiced view is that there is no particularly good
-> search tool out there yet.  Of course, that means opportunity! for
-> those of us trying to make better search tools...

Maybe I'm going one level more cynical than you, but I also think the
dearth of effective tools (and the ubiquity of mediocre ones) points to
the difficulty of the problem.  So the opportunity has to be weighed
against the likelihood that this is just a real hard problem...

thanks,
--titus

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