[BBF Standards] data exchange issue 1: Abstraction

Ralph Santos rasantos at lbl.gov
Tue Feb 26 22:10:34 EST 2008


Reshma,

Thanks for posting this, it clarifies a lot.  Do you think it would be 
appropriate to add your answer to Herbert's questions to the biobrick 
definition under "What is a biobrick?" on the web page?  I think your 
answer adds some useful points and important details.

---ralf

Reshma Shetty wrote:
> Hey all,
>
> First off, great discussions going on on the list.  Specifically, to
> answer Herbert's questions ...
>
> *A biological part is a DNA sequence that encodes a basic biological function.
>
> *Biological parts that conform to prescribed technical standards are
> standard biological parts.
>
> *Parts that conform to the BioBrick assembly standard are BioBrick
> standard biological parts.  Additional technical standards defining
> BioBrick standard biological parts will be set via an open standards
> setting process led by The BioBricks Foundation.
>
> [Note: parts do not include either the plasmid that propagates that
> part or sequences whose function is to help physically compose parts
> (e.g., the BioBrick prefix and suffix).  Parts can come in different
> formats (the BioBrick standard, the BamHI/BglII standard promulgated
> by folks at Berkeley, no "scar" sequences whatsoever because of direct
> synthesis etc.)]
>
> *Devices are combinations of one or more parts that have a
> human-defined function.  I prefer an even more specific definition in
> which devices not only have human-defined function but also are
> functionally composable using common signal carriers such as
> transcription rate (PoPS), translation rate (RiPS), phosphorylations
> per second etc.  Devices can have an input of a common signal carrier,
> an output of a common signal carrier or both.  For instance, a
> promoter is both a part (its basic biological function is to initiate
> transcription) and a device (its human-defined function is a PoPS
> source and it produces the common signal carrier PoPS).  A
> transcriptional inverter is a device since  logical "NOT" is a
> human-defined operation and an inverter has an input of PoPS and an
> output of PoPS.
>
> Some confusion arises because in the Registry of Standard Biological
> Parts, everything with a BioBrick part number is called a part.  The
> Registry distinguishes between basic parts (equivalent to "biological
> part" definition above) and composite parts (combinations of two or
> more basic parts).  Based on the definitions above, a device can be
> either a basic part or a composite part.  But not all basic or
> composite parts are devices.
>
> It is not clear whether we need to reconcile the Registry's
> terminology with that of parts versus devices described above or if
> both sets of definitions can stand in parallel since they serve
> slightly different purposes.
>
> -Reshma
>
> On Tue, Feb 26, 2008 at 11:12 AM, Herbert Sauro <hsauro at u.washington.edu> wrote:
>   
>> Drew, I'm not try to be difficult here, but can you also indicate what
>>  you mean by a basic biological function. The other thing that confuses
>>  me is what is the difference between a device and a part because if a
>>  part can also be a composite then what is a device?
>>
>>  Herbert
>>
>>
>>
>>  Drew Endy wrote:
>>  > A BioBrick part is any basic biological function that can be encoded
>>  > as DNA.
>>  >
>>  > More specifically, I believe that there are already parts in the
>>  > Registry encoding components from the Fim system, as well as sites
>>  > recognized and acted on by invertases.
>>  >
>>  > I'll try to dig up the part numbers once I get back from teaching class.
>>  >
>>  > Expect more emails from me today about Saturday's workshop too!
>>  >
>>  >
>>  >
>>  > On Feb 26, 2008, at 10:59 AM, Deepak Chandran wrote:
>>  >
>>  >> Concerning systems such as Fim, I don't think that they are individual
>>  >> parts. Rather, they are a composition of parts (i.e. "devices").
>>  >> Hence,
>>  >> the whole Fim system should not be stored as a single part. Other
>>  >> systems, such as the Sin operon, also have multiple coding regions
>>  >> with
>>  >> promoters in between them -- I don't think that they should be
>>  >> considered "parts".
>>  >>
>>  >> Ralph Santos wrote:
>>  >>> Sorry, I should have responded initially by responding to your
>>  >>> direct question rather than trying to rethink everything.
>>  >>> Regardless of what you think of alternative strategies, the current
>>  >>> representation should be explored fully, and pretty much any data
>>  >>> exchange system regarding biobricks has to deal with sequences at
>>  >>> some point.
>>  >>>
>>  >>> Considering the unresolved questions:
>>  >>>
>>  >>>> From the way I read your points, it seems that whether points (A)
>>  >>>> and (B) are related depends upon how one defines the relationship
>>  >>>> between a biobrick and its sequence.
>>  >>> With part (A), it occurs to me that there's several ways to deal
>>  >>> with the unresolved question.  One can directly attack it and
>>  >>> resolve it here and now, or one can find a way to allow the process
>>  >>> to move forward without resolving it.
>>  >>>
>>  >>> As you rightly point out, defining a biobrick in terms of its
>>  >>> sequence raises a bunch of issues, but is it absolutely necessary
>>  >>> to define a biobrick in terms of its sequence?  If we define the
>>  >>> standard to demand this assertion, then the answer is yes, but one
>>  >>> can define the data exchange process so that one can dance around
>>  >>> the issue.
>>  >>>
>>  >>> One simple way to dance around the issue is to stipulate that
>>  >>> biobrick data exchange systems must assign every sequence its own
>>  >>> accession ID so that it can be identified independently from the
>>  >>> biobrick with which it's associated.  For the sake of simplicity,
>>  >>> we can bury this ID so that you don't have to deal with it if you
>>  >>> don't want to, while still providing some means to get these
>>  >>> sequence ID's if you want them.
>>  >>>
>>  >>> In this scheme, the rules for managing biobrick sequences would be
>>  >>> governed by the principle that you should be able to pretend
>>  >>> there's only one sequence associated with a biobrick.  So no matter
>>  >>> how many sequences are associated with a biobrick, only one will be
>>  >>> regarded as primary, to be returned with standard queries.  Digging
>>  >>> into the other sequences should require some sort of specialized
>>  >>> call specifically defined to retrieve these other sequences.  Of
>>  >>> course, deleting a biobrick should imply that all of the sequences
>>  >>> associated with it are deleted.
>>  >>>
>>  >>> I guess this solution most closely resembles what you refer to as a
>>  >>> 'biobrick implementation' layer underneath.  I like this way of
>>  >>> handling it because it allows folks who wish to assume a simple one-
>>  >>> to-one relationship between bricks and sequences to think that way,
>>  >>> but it allows the distinction to be monitored and dealt with behind
>>  >>> the scenes.
>>  >>>
>>  >>> Having said all that, there is a situation worth thinking about,
>>  >>> because it favors the family concept and it forces one to think
>>  >>> about what the sequence means.  There are systems like the "fim"
>>  >>> system in E. Coli:
>>  >>>
>>  >>>  http://jb.asm.org/cgi/content/full/182/10/2953
>>  >>>
>>  >>> Basically it activates transcription for one of two genes depending
>>  >>> upon its orientation.  If one thinks of a sequence as defining a
>>  >>> molecule, something like the fim system causes some headaches.  Two
>>  >>> people could put in what amounts to the same molecule in two
>>  >>> different orientations and the system would not be able to
>>  >>> recognize it as such.  Of course if one imagines biobricks being
>>  >>> made incorporating multiple fim elements one can see the number of
>>  >>> possible sequences for the same brick growing combinatorially.  It
>>  >>> may be rare enough that the issue may be safely ignored (I don't
>>  >>> know myself).  One may wish to use the brick family idea to try and
>>  >>> capture all the possible sequence states or configurations.
>>  >>>
>>  >>> If in part (B) by "format" you're referring to the actual file
>>  >>> format (i.e. FASTA vs. GENBANK vs. EMBL etc.) I'd prefer to see us
>>  >>> deal with that as a matter of presentation to the user, and not
>>  >>> consider sequence formatting as part of the definition of a
>>  >>> sequence (or biobrick for that matter).  As far as tools go, It
>>  >>> would simplify things if we focused on tools doing most of their
>>  >>> processing in a single canonical format, and stipulate that there
>>  >>> will be conversion tools to preprocess inputs into that canonical
>>  >>> format and postprocess them however the user wishes to see them.
>>  >>> That would also fit well with the IETF's principle of being liberal
>>  >>> with what one accepts for input, being conservative with what one
>>  >>> emits for output.
>>  >>>
>>  >>>
>>  >>>
>>  >>> ----- Original Message -----
>>  >>> From: Raik Gruenberg <raik.gruenberg at crg.es>
>>  >>> Date: Monday, February 25, 2008 3:18 pm
>>  >>> Subject: [BBF Standards] data exchange issue 1: Abstraction
>>  >>> To: standards at biobricks.org
>>  >>>
>>  >>>
>>  >>>> Hi all,
>>  >>>>
>>  >>>> your 1st of March meeting is approaching and I would like to focus
>>  >>>> the
>>  >>>> discussion back to more mundane data exchange problems -- let's try
>>  >>>> to have some
>>  >>>> draft ready which is covering:
>>  >>>>
>>  >>>> (1) Aim / Application scenarios for this standard
>>  >>>> (2) What is a Biobrick?
>>  >>>> (3) Datamodel 1 -- minimal Biobrick information
>>  >>>>
>>  >>>> This should be doable in the remaining time (just think: "yes we
>>  >>>> can!" :-)
>>  >>>>
>>  >>>> Let's start with (2). The current state of debate is as always here:
>>  >>>> http://openwetware.org/wiki/The_BioBricks_Foundation:Standards/Technical/Exchange#What_is_a_Biobrick.3F
>>  >>>>
>>  >>>> We have two (related) unresolved questions in this section:
>>  >>>>
>>  >>>> (A) If a Biobrick is defined by its unique sequence, already a
>>  >>>> minor variation
>>  >>>> (e.g. silent mutation) of this sequence creates an entirely new
>>  >>>> biobrick. We may
>>  >>>> want to create the concept of Biobrick-families on top of the
>>  >>>> Biobrick or one
>>  >>>> could introduce a 'biobrick implementation' layer underneath.
>>  >>>>
>>  >>>> (B) Even worse, what happens if I put the exactly same sequence
>>  >>>> into a different
>>  >>>> format? Is that a new Biobrick? -- Only then can we include a
>>  >>>> "Format" record in
>>  >>>> the minimal data model. For the experimentalist this information is
>>  >>>> essential.
>>  >>>> Moreover, I think we need a second definition of "Device" (built
>>  >>>> from
>>  >>>> biobricks). Some of the discussions we had here may overlook that a
>>  >>>> single
>>  >>>> Biobrick will often *not* encapsulate a self-standing function but
>>  >>>> will often
>>  >>>> depend on additional biobricks that are not fused to it on the DNA
>>  >>>> level and may
>>  >>>> even be distributed over different cells (e.g. the quorum sensing
>>  >>>> device). I
>>  >>>> think we should treat this with a separate "Device" concept. Some
>>  >>>> Biobricks may
>>  >>>> turn out to be self-sufficient devices, most others not. Some
>>  >>>> functional
>>  >>>> characterizations (Pops-in/out) only make sense for full devices,
>>  >>>> but not for
>>  >>>> every single Biobrick.
>>  >>>>
>>  >>>> Comments?
>>  >>>> Greetings,
>>  >>>> Raik
>>  >>>>
>>  >>>> --
>>  >>>> ________________________________
>>  >>>>
>>  >>>> Dr. Raik Gruenberg
>>  >>>> http://www.raiks.de/contact.html
>>  >>>> ________________________________
>>  >>>>
>>  >>>> _______________________________________________
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>>  >>>>
>>  >>>>
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