[BBF Standards] Two separate standards
Deepak Chandran
deepakc at u.washington.edu
Wed Mar 19 18:13:42 EDT 2008
Hello Raik, John, Ralf, and rest,
I just want to see if I understand this clearly. Suppose I design a
composite part:
promoter---gene1---terminator1---gene2---terminator2
Suppose gene2 is transcribed at 50% the rate of gene1, due to the
presence of terminator1. The composite part would not contain this
information, which is fine depending on how it will be used. Now,
suppose someone sees this as a very useful device, then that person can
take the same construct and characterize it so that it is a properly
defined device. Is this correct?
I think Ralf's idea of use cases would be very helpful in identifying
what people would like from a well characterized part and device, which
may pave the road for standard definitions. There are several cases such
as hybrid promoters (eg. Tac), fused proteins (eg. GFP), separated
protein domains (eg. Beta-gal), etc. that are frequently used in
biology, and I don't know how many people would like this information
accessible in a standard format. Or is all this to be thrown in the
"annotation" area? Again, use cases might be able to resolve such issues.
--Deepak
Raik Gruenberg wrote:
> Hi Josh, Hi Deepak,
>
> sorry about the late contribution...
> the cost/benefit issue should definitely be kept in mind. I go along
> with Josh's analysis below but would say that the concept of a
> composite part has a clear benefit for part and device designers which
> outweighs the cost to the tool designer. (1) It allows part designers
> to track the pedigree of their parts as they assemble them. (2) It
> removes redundancy from the database. (3) It affords some simple
> visualization of a parts content (see the part sketches generated by
> the registry). (4) It encourages the formulation of smaller parts with
> increased re-usability.
>
> On the other hand it would increase the cost and complexity
> enormously, if composite parts would also need to include wiring
> diagrams for simulation or similar purposes. This should be uncoupled
> from the part information and can be dealt with in the description of
> "Biobrick devices".
>
> My conclusion would be: We need composite parts but they should have
> exactly the same description as basic parts with only one difference:
> the DNA sequence is replaced by a sequence of basic parts (plus
> scars). What we may want to include with a part (composite or not)
> though is basic biochemical information like mRNA and protein
> stabilities or whatever applies to this particular type of part.
>
> Greetings,
> Raik
>
> Josh Perfetto wrote:
>> Hi Deepak,
>>
>> I would suggest that in evaluating questions regarding whether a
>> provision
>> for something should be incorporated into a standard, we use a
>> framework of
>> what the benefits and costs would be to the various parties involved,
>> rather
>> than focus on what would be the best way to model the system and
>> reflect all
>> of its complexities, as these are really separate goals.
>>
>> For example, I think the primary purpose of publishing standardized
>> descriptions of "parts" is so that these parts may be used by device
>> designers. At a high-level, device designers really need two things
>> when
>> using a part:
>>
>> 1. A description of what the part does in sufficient detail,
>> legal/technical
>> restrictions on its use, etc.
>> 2. Sufficient information to allow them to physically incorporate the
>> part
>> into their device
>>
>> It's obviously the purpose of the standard to define how exactly to
>> do this.
>> Incorporating a DNA sequence into the part definition would address
>> much of
>> #2.
>>
>> Now consider the composite part, and adding a provision to the
>> standard so
>> that these parts can described in a manner similar to non-compose parts
>> (thus addressing #1), but rather than defining these parts by a DNA
>> sequence, addressing #2 by pointing to the various individual parts
>> which
>> are part of this composite part, which in turn already define their
>> own DNA
>> sequences. What would the consequences be?
>>
>> - The device designers would be equally happy (but no happier): they
>> still
>> know exactly what the composite part does because it has its own
>> description, and their software tools can pull the DNA sequences out
>> of the
>> sub-parts and combine them together to generate the overall DNA
>> sequence to
>> synthesize for a device, so it's just as easy for them as before.
>>
>> - The tool designers are less happy: since the BioBrick Part standard
>> is now
>> more complex, more work has to go into the software implementation
>> for the
>> various tools. This additional complexity is actually the main
>> drawback:
>> the standard may be no more than a few paragraphs on a wiki now, but
>> these
>> things have the tendency to grow and grow, so it's essential to avoid
>> unnecessary complexity until it's needed.
>>
>> - The designers of composite parts may be slightly happier: They may in
>> theory have slightly less work to do to publish their part since they
>> don't
>> have to keep track of the concatenated DNA sequences. And their work
>> may be
>> more transparent since you can clearly see what parts they combined from
>> their part definition. But I would argue that this shouldn't be the
>> purpose
>> of a parts standard, and that if one wanted to really understand the
>> internals of a composite part, they would probably need to read a
>> paper or
>> additional documentation from the parts' designer anyways.
>>
>> In this analysis at least it would seem there is little benefit in
>> treating
>> composite parts specially in the standard unless they are very
>> numerous as
>> there are real costs but few benefits. You may know about benefits of
>> treating composite parts specially that I am missing and would change
>> this
>> analysis, which would be fine-- I am mainly suggesting that we focus
>> primarily on the cost/benefits in answering questions like you
>> asked. This
>> is one area where the use cases that Ralph suggested would come in
>> handy, as
>> it would lead to agreement on who/what we are trying to benefit, which
>> specific proposals could be evaluated against.
>>
>> Just my two cents,
>>
>> -Josh
>> -----Original Message-----
>> From: standards-bounces at biobricks.org
>> [mailto:standards-bounces at biobricks.org] On Behalf Of Deepak Chandran
>> Sent: Monday, March 17, 2008 12:14 PM
>> To: Drew Endy
>> Cc: standards at biobricks.org
>> Subject: Re: [BBF Standards] Two separate standards
>>
>> Drew,
>>
>> Agreed: we do not care about non-functional composite parts.
>> But is the solution to throw them into the pile of "parts"? You had
>> mentioned some weeks ago that the fimH transcription unit (can't seem
>> to find that link) is a part, not a device; if I remember correctly,
>> it has two promoters/operators that are regulated separately. Such a
>> construct seems to match the descriptions of a device, not a part. Is
>> this correct?
>>
>> --Deepak
>>
>> Drew Endy wrote:
>>> Deepak,
>>>
>>> One of the great strengths underlying synthetic biology is that we
>>> get to invent what we hope to construct (and depict).
>>>
>>> We don't have to describe everything that already exists. We also
>>> don't have to describe everything that could be [trying to describe
>>> everything is one of the great costs, challenges, and at times,
>>> failures of systems biology.
>>>
>>> So, in this context, let me ask you a question...
>>>
>>> Do we really care about composite parts that are not properly
>>> defined devices?
>>>
>>> Wouldn't this be like Texas Instruments worrying about every
>>> possible combination of transistors, resistors, and capacitors.
>>> Instead TI only considered combinations of parts that resulted in
>>> useful devices, and they described only these objects in their
>>> Transistor Transistor Logic Data Book.
>>>
>>> The only time I've ever seen combinations of parts that are not
>>> themselves well defined devices being tracked electronically is
>>> during a semi-automated BioBrick standard assembly process. In this
>>> case, the build intermediates need to be tracked during a
>>> ligation-based DNA assembly process. Randy Rettberg developed a
>>> software tool to handle this
>>> [http://parts.mit.edu/r/parts/assembly/index.cgi]
>>>
>>> In any case, remember that we don't have to describe *every* thing,
>>> only those things that we care enough to try to make and use.
>>> Standards restrict and delimit some possibilities in order that work
>>> goes forward and more exciting possibilities can come true.
>>>
>>> Cheers!
>>> D.
>>>
>>> On Mar 17, 2008, at 12:38 PM, Deepak Chandran wrote:
>>>
>>>> Drew,
>>>>
>>>> This description is clear. The confusion comes when you allow
>>>> parts made from other parts to be categorized as "parts" as well --
>>>> how can this be? At the same time, they may not be devices either
>>>> because they do not have proper interfaces.
>>>>
>>>> --Deepak
>>>>
>>>> Drew Endy wrote:
>>>>> Exactly correct.
>>>>>
>>>>> DNA engineers will be concerned with how to construct DNA.
>>>>>
>>>>> Parts engineers will be concerned with how to build parts at the
>>>>> primary nucleic and amino acid sequence level (and whatever else
>>>>> synthetic biological parts get made from).
>>>>>
>>>>> Device engineers will be concerned with how parts are best
>>>>> organized to make devices.
>>>>>
>>>>> System engineers will be concerned with how devices are best
>>>>> organized to make systems.
>>>>>
>>>>> Each type of engineer needs to be able to communicate at least
>>>>> one level "down" and "up" in this abstraction hierarchy. Such
>>>>> communication should be limited and well structured.
>>>>>
>>>>> Meanwhile, I don't mean to add fuel to any "larger than life T7
>>>>> autogene fires," but check out the last 6 pages from the
>>>>> synthetic biology comic book, if you've not seen it before.
>>>>>
>>>>> http://www.nature.com/nature/comics/syntheticbiologycomic/index.html
>>>>>
>>>>> Pages 7-8 detail making a device from parts.
>>>>>
>>>>> Pages 9-12 detail some issues of common signal carriers for
>>>>> transcription based devices.
>>>>>
>>>>> Cheers!
>>>>> D.
>>>>>
>>>>>
>>>>>
>>>>>
>>>>> On Mar 15, 2008, at 2:11 PM, Herbert Sauro wrote:
>>>>>
>>>>>
>>>>>> I think Deepak has made a useful observation. At one level an
>>>>>> engineer
>>>>>> won't care about the DNA sequence, of more interest is the
>>>>>> functional
>>>>>> properties of the boxes he/she is putting together. On the other
>>>>>> hand,
>>>>>> the designer of functional boxes will be concerned with the DNA
>>>>>> sequence
>>>>>> since in designing for example a promoter or gene with a specific
>>>>>> property the DNA sequence is clearly paramount. It looks like
>>>>>> there may
>>>>>> be a natural separation here.
>>>>>>
>>>>>> Herbert Sauro
>>>>>>
>>>>>>
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>>>>>
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