[Biopython-dev] Bio.Motif Suggestions

Tue Apr 21 15:59:32 UTC 2009

Hi,

thanks for your suggestions.

To make the long story short:
- I mostly agree with your points
- I've updated the wiki page to include your requests
http://biopython.org/wiki/MotifDev
- I'll definitely spend some time working on particular requests and
then post specifically.

cheers
Bartek

On Tue, Apr 21, 2009 at 10:34 AM, Leighton Pritchard <lpritc at scri.ac.uk> wrote:
> Hi,
>
> Some thoughts and a bit of a wishlist...
>
> On 20/04/2009 16:04, "Bartek Wilczynski" <bartek at rezolwenta.eu.org> wrote:
>
>> On Mon, Apr 20, 2009 at 4:35 PM, Peter <biopython at maubp.freeserve.co.uk>
>> wrote:
>>>
>>> What would a space in a motif mean?  Clearly something different from
>>> a wildcard like N or X in nucleotide or protein sequences.  Does it
>>> mean a gap of variable length?  If it means a gap of one character
>>> then surely just using a "-" would be sensible (as used in multiple
>>> sequence alignments), for which we have a gapped alphabet system
>>> setup.
>>>
>> I think that once we start talking about gapped motifs, we are really
>> talking about
>> multiple alignments on steroids. This hasn't been done so far because you
>> don't
>> really need it for DNA motifs,
>
> It might not be required for the motifs you've been working with, but we've
> been doing profile-based searches for bipartite regulatory binding sites in
> DNA.  These sites have a variable-length spacer region, and so require
> gapped alignments for building motifs.  The spacer region consensus
> (depending on the level of identity required for the consensus) is usually
> composed of Ns.
>
> I guess that this comes down to whether we choose to restrict the meaning of
> "motif" to an ungapped string of symbols (including ambiguity) representing
> nt/aa, or whether we want to permit the inclusion of variable-length gaps,
> regions, or ambiguities in a PROSITE or regular expression-like manner (e.g.
> C-x(2,4)-C-x(3)-[LIVMFYWC]-x(8)-H-x(3,5)-H, GAACC.{17,21}AAC or
> C{,3}A{3,5}TTTT).  Although profile methods like HMMer can produce a
> consensus output that looks like an ungapped string of symbols to represent
> a motif, it doesn't capture important features of the HMM representation.
>
> I think the latter representations are more useful, even if harder to
> code/maintain.  I think that leaving them out would be a glaring hole in
> functionality, and that they're a target Biopython should aim for.
>
>> I think it would be great to be
>> able to easily
>> convert multiple alignments into motifs. This would allow us to  use
>> the power of
>> BIo.AlignIO for IO and Bio.Motif for searching and comparisons.The question is
>> how to design API for these  functions.
>
> I agree.  I think that there's another important question: what do we mean,
> and need to do, when we talk about converting an alignment into a motif?
> Consensus/majority and PSSM methods from a sequence alignment should be
> straightforward to implement in Python - even for gapped alignments.
> Including a representation of variable-length gaps might be a little more
> difficult, and storing an HMM representation may be too much to manage
> immediately.  That's still three different types of object - with likely
> different components to their interfaces - to be stored.  In their
> relationship to a source alignment, these representations could be
> properties of a single alignment, or independent Bio.Motif objects (perhaps
> each with a link back to their parent alignment).
>
> The results of searches are also likely to be qualitatively different,
> depending on the type of motif used for the search, and the results desired
> by the user.
>
> I think that, for anything other than simple searches (string search,
> regex), we'd be on a hiding to nothing by implementing search methods within
> Python.  It's not likely to be as fast as dedicated search packages, and it
> would be a headache for maintenance.  So, with apologies if I missed this
> part of the discussion or documentation, it seems to me that Bio.Motif could
> be most powerful in the alignment/searching/comparison process as a 'broker'
> within BioPython, providing a consistent API for interface with external
> alignment/search/comparison applications that also permits programmatic
> manipulation of the profile/HMM/alignment.  E.g.
>
> align = Bio.AlignIO.read(alignfilehandle)
> consensus = align.build_consensus(threshold=0.9)
> pssm = align.build_pssm()
> hmmer = align.build_hmmer()
> hmm = align.build_hmm(order=3)
>
> Or
>
> consensus = Bio.Motif.consensus_from_alignment(align, threshold=0.9)
> pssm = Bio.Motif.build_pssm_from_alignment(align)
> hmmer = Bio.Motif.build_hmmer_from_alignment(align)
> hmm = Bio.Motif.build_hmm_from_alignment(align, order=3)
>
> (which I don't think is as neat an interface, even if all
> align.build_consensus does is call the Bio.Motif.consensus_from_alignment
> method)
>
> Followed by things like
>
> pssm.consensus()
> pssm.logo()
> hmm.generate_sequence(length=100)
> hmm.to_graphviz()
>
> And then the consensus, pssm, hmm and hmmer objects could be used as input
> to interfaces for the relevant applications.
>
> Converting an alignment into an HMM for this purpose may itself benefit from
> a call to HMMer's hmmbuild (and Pythonic representation of the data
> structure), rather than implementation of an equivalent internal function -
> even though I think one of those would be useful, too.
>
> Cheers,
>
> L.
>
> --
> Dr Leighton Pritchard MRSC
> D131, Plant Pathology Programme, SCRI
> Errol Road, Invergowrie, Perth and Kinross, Scotland, DD2 5DA
> e:lpritc at scri.ac.uk       w:http://www.scri.ac.uk/staff/leightonpritchard
> gpg/pgp: 0xFEFC205C       tel:+44(0)1382 562731 x2405
>
>
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-- 
Bartek Wilczynski
==================
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EMBL, Furlong group
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