[BBF Standards] Two separate standards

[Raik Gruenberg]

Sorry, maybe an example describes it better.

I think, your concern about exchanging parts within devices and having a more 
abstract view on them would be solved with the Biobrick family and Device family 
concept (see Wiki, it's not very well formulated yet).

So take the "Switch.1" in the PolkaDork/E. colibrator system:
http://parts.mit.edu/wiki/index.php/IAP2004:Polkadorks

- Device Switch.1 is composed of 4 exactly defined composite parts with unique 
sequence (of basic parts with unique sequence)

This gives you an exact and reproducible description of the device -- it is very 
important for someone who wants to take the blueprint and implement exactly this 
device in E. coli. However, let's say you want to transfer this part into yeast.
Left like this, the description doesn't help you. You need a more abstract view 
instead.

- Switch.1 could be assigned to a device family "conditional AND" which would be 
a sub-family of "PoPS devices"
- At the same time, Switch.1 could also be assigned to device family "E. coli 
intracellular devices" which would be a direct or indirect subfamily of 
"intracellular devices"

Your first attempt would now be to search the Registry 2.0 for a device 
belonging to family (or subfamily of) "conditional AND" but also family "Yeast 
intracellular devices". If it exists, you are done (if the quantitative 
parameters are right).

If this search fails, you would look at the Biobricks forming the Switch.1 Each 
of them would again belong to different Biobrick families and you would now try 
to identify the closest matching Biobricks that are also compatible with yeast.

The interesting question is then how to draw family boundaries and family 
hierarchies. This should, IMO, be left open by the basic standard. It will 
evolve together with the field. Your idea to work through all iGem projects 
could be extremely helpful for getting a first handle on this problem.

So that's kind of my vision how things could work in a bright future. There is 
still some fuzziness in the family concept when it comes to where the 
quantitative data belong. Logically, they should belong to the exact unique 
device. The device family would then only specify what properties to expect from 
its members. But devices in a family may perhaps also share quantitative 
characteristics or fall into a certain range of specifications...

Have a nice weekend!
Raik

Deepak Chandran wrote:
> Hello Josh, Drew, and rest,
> 
>    While it seems logical to first have standard definitions for 
> promoter, rbs, coding regions, terminators, etc. before working on 
> standards for devices and systems, I think the two are somewhat 
> independent. People have been building biological circuits successfully 
> (iGEM students for example). What I am proposing is for some of us 
> (myself included) to write out a format that can represent all of the 
> iGEM projects. This format can allow others to take iGEM projects (and 
> any other such projects) and connect them together to form larger 
> circuits without having to understand the details of the project itself. 
> All these circuits will be represented in the standard language so that 
> one does not need to reconstruct an entire device to reuse it. I think 
> this is very much possible while the standards on promoters/rbs/etc are 
> still pending. It is also a bit easier maybe, because many concepts can 
> be borrowed from engineering disciplines.
> 
> --Deepak
> 
> Josh Perfetto wrote:
>> I think you are making some very insightful remarks without realizing it :)
>> The only way to engineer large-scale systems is by breaking the system down
>> into modular units with well-defined interfaces, otherwise it just gets too
>> complex.  The circuit diagram analogy is perfect: inputs, black boxes, and
>> outputs, and I think it is a reasonable representation at this level.  If we
>> are defining things at this level, and have well-defined interfaces like
>> PoPs for inputs and outputs, then I agree with you that it is not necessary
>> to specify the DNA sequence of the entire circuit, but rather just define
>> the order of the black boxes, which can define their own DNA sequences.  You
>> can replace one black box of the circuit diagram with another and predict
>> what will happen.  Once we standardize how to specify devices at this level,
>> including devices with multiple inputs, it will be very powerful.
>>
>> When we drill down into other levels, like the upstream and core portions of
>> a promoter, obviously PoPs is a totally useless interface for defining how
>> these parts fit together, and so a circuit diagram is not appropriate for
>> specifying the workings of a promoter as you said.  We need to decide at
>> which levels standardization would be useful and how to define interfaces
>> between parts at these useful levels.  However I don't think it's essential,
>> at this stage, to model the world.  For example, if we want to standardize
>> how to define promoter behavior, we can leave the internals of promoter
>> working as a black art, or at least out of the scope of standardized parts,
>> and only define the characteristics of the promoter at that level, at least
>> for now.
>>
>> I have not been in this community very long and am unsure about the exact
>> definition that others are attributing to the term "devices" (and I think
>> this does vary a bit, perhaps because it is not yet standardized :) ).  But
>> I don't see any problem with defining devices formally in terms of A) PoPS
>> in/out, and B) other modifiers like UV/LuxR.  I think a key question is how
>> much these other modifiers from B are standardized in their definition vs.
>> how much this is an ad-hoc definition.  I think it's probably best to follow
>> the 80/20 rule and standardize the 20% of properties that have are used 80%
>> of the time, like chemical concentration, where the chemical in question is
>> defined by something like CAS registry number, while leaving the other
>> specialized properties that some devices might measure, like magnetic field
>> orientation, unstandardized.
>>
>> -Josh
>>
>>  
>>
>> -----Original Message-----
>> From: Deepak Chandran [mailto:deepakc at u.washington.edu] 
>> Sent: Friday, March 14, 2008 7:24 PM
>> To: Josh Perfetto
>> Cc: 'Drew Endy'; standards at biobricks.org
>> Subject: Re: [BBF Standards] Two separate standards
>>
>> Hello Josh and Drew and rest,
>>
>> The Polkadots system is a great example. Basically what I am saying is 
>> that the sequence doesn't need to be specified in order to define the 
>> polkadots system. As long as I know the parts and the order in which 
>> they are placed on the plasmid(s), I can reconstruct the system. By 
>> "interaction between parts", what I mean is that in order to understand 
>> how polkadots is working, I need to see the circuit that is presented on 
>> the polkadots website. It would be nice if the circuit diagram was our 
>> standard representation, but that is not reasonable.
>>
>> I think an operon is a similar case -- it is a very simple circuit. One 
>> can draw a diagram that explains how an operon functions. So, I am 
>> looking at operons as engineered objects (though humans didn't engineer 
>> them first).
>>
>> What I am proposing is that circuits such as polkadots or even operons 
>> should be defined in such a way that a synthetic biologist can cut out 
>> one of the components of the circuit and replace it with another 
>> device/part. If we cannot do that, then these biological circuits are 
>> not engineerable.
>>
>> On the contrary, a promoter is different. I don't know how one can 
>> explain the inside of a promoter using a circuit diagram. The fact that 
>> promoters can be broken down into smaller components is true. But can 
>> you take the first half of one promoter and stick it to the second half 
>> of another promoter (I don't know)? Would the resulting promoter have 
>> predictable behavior? Similarly, can I take pieces of two RBS and piece 
>> them together and be able to predict the function of the resulting RBS? 
>> In constast, replacing the promoter or RBS inside an operon has 
>> predictable behavior, and the affect of replacing parts inside the 
>> polkadots can also be predicted (just like I can predict the result of 
>> changing my computer's CPU). I suppose one could say replacing protein 
>> domains has predicable behavior.
>>
>> By "interaction between parts", I did not mean any particular type of 
>> interaction. But I was not clear on this: is PoPS the standard 
>> input/output for BioBrick parts? Does this mean that I cannot have a 
>> device that uses UV as an input and/or produces LuxR as an output?
>>
>> --Deepak
>>
>> Drew Endy wrote:
>>
>>   
>>> Not true.  A promoter can be disassembled, for example in bacteria, 
>>> into -10 and -35 regions.
>>>
>>> You may find it helpful to stop thinking about natural objects such as 
>>> operons and start thinking about devices as *engineered* objects.
>>>
>>> For example, consider the material produced in 2004 by the Polkadorks:
>>>
>>> http://parts.mit.edu/wiki/index.php/IAP2004:Polkadorks
>>>
>>> In the Polkadorks work you can see that they clearly defined device 
>>> boundaries based on PoPS, including PoPS pass-through boundaries 
>>> leading to multi-device mRNA. 
>>>     
>> Josh Perfetto wrote:
>>   
>>> Hi Deepak,
>>>
>>> I think that the view that a promoter cannot be sub-divided reflects a
>>> particular level of interest.  From another point of interest, it would be
>>> very interesting to break promoters down into UPE, spacers, core
>>>     
>> promoters,
>>   
>>> boxes, etc., and look at the "interactions within the part" with factors
>>> like UBF1.
>>>
>>> You are bringing up an interesting point with your operon.  There are a
>>> couple ways you could define an operon.  For example, you could create an
>>> operon sensitive to a specific repressor, and define it in part by a
>>> function that relates the concentration of that repressor to the level of
>>> polymerase that will flow out.  Or, you could define it in such a way as
>>>     
>> it
>>   
>>> has an interchangeable repressor sub-part, and define the operon in part
>>>     
>> by
>>   
>>> a function which is dependent on another function defined by the sub-part
>>> part definition.
>>>
>>> If we were to take the first approach, it doesn't mean that the operon
>>>     
>> can't
>>   
>>> be decomposed which obviously it can, it just means that such
>>>     
>> decomposition
>>   
>>> is not an interface of the part, but an internal detail of the part.  The
>>> second approach doesn't represent the ability to arbitrary combine parts
>>>     
>> and
>>   
>>> be able to predict what will happen, but rather a part which is
>>>     
>> specifically
>>   
>>> designed to take another part of a specific type and as a parameter and
>>> predict what will happen.
>>>
>>> But stepping back for a moment, aren't we now really discussing devices?
>>> I.e. the first approach is a single device with a PoPs out that's
>>>     
>> dependent
>>   
>>> on a specific repressor, while the second approach is two devices, the
>>>     
>> first
>>   
>>> with a PoPs out, and the second that relates its PoPs in and the level of
>>>     
>> a
>>   
>>> specific repressor to produce a PoPs out value?  When you say "the 
>>> interaction between the parts is the crucial information", it seems that
>>> you're really either talking about an interface in terms of PoPs (in which
>>> case these parts could be called devices at least in my understanding of
>>>     
>> how
>>   
>>> the term is being used), or are proposing that another interface besides
>>> PoPs be standardized in the definition of parts.
>>>
>>> -Josh
>>>   
>>> -----Original Message-----
>>> From: standards-bounces at biobricks.org
>>> [mailto:standards-bounces at biobricks.org] On Behalf Of Deepak Chandran
>>> Sent: Friday, March 14, 2008 2:31 PM
>>> To: Drew Endy
>>> Cc: standards at biobricks.org
>>> Subject: Re: [BBF Standards] Two separate standards
>>>
>>> Drew,
>>>
>>> The parts,devices,systems hierarchy is fine. What is confusing to call 
>>> an entire operon (possibly more than one promoter, rbs, gene) a "part" 
>>> and a simple promoter a "part" as well. I can take an operon apart and 
>>> replace one of the rbs, whereas the promoter cannot be taken apart. 
>>> There is a difference between these two from an engineering perspective.
>>>
>>> I think that the operon should be defined in terms of the parts that it 
>>> is made from and how they are interacting. Each individual part would 
>>> then contain the sequence information and other characteristics. For 
>>> anything made from multiple parts (say a bistable switch), the 
>>> interaction between the parts is the crucial information. But if you 
>>> take a basic part like a promoter, there is no interaction within the 
>>> part. This is why I think that the standard definitions for basic parts 
>>> and parts made from more than one part should be different.
>>>
>>> Again, I am completely open to disagreement here. It would be sufficient 
>>> to explain how you can apply the same standards to describe a bistable 
>>> switch and a promoter.
>>>
>>> --Deepak
>>>
>>> Drew Endy wrote:
>>>   
>>>     
>>>> Parts are parts.  I'd use the language basic parts if you need a 
>>>> modifier.
>>>>
>>>> Devices are composite parts.  But, not all combinations of parts are 
>>>> devices.  Devices are limited by the requirements bounding device 
>>>> specification.  For example, polymerase per second (PoPS) serves to 
>>>> define a common signal carrier for inputs and outputs when dealing 
>>>> with gene expression devices.
>>>>
>>>> Note that there is no absolute physical definition of a part.  You can 
>>>> keep drilling down into particles and sub-atomics.  So, I believe that 
>>>> the standards should be linked to the human-invented abstraction 
>>>> hierarchy (i.e., parts, devices, systems), which was invented for 
>>>> practical reasons (i.e., it is good for something).  Support for 
>>>> reliable physical and functional composition is definitely one of the 
>>>> first and best goods that we can have.
>>>>
>>>> For the small amount of protein engineering work going on.  Docking 
>>>> and phosphorylation motifs are typically though of as parts.  For the 
>>>> small amount of RNA engineering work going on, aptamers and ribozyme 
>>>> active sites are also thought of as parts.
>>>>
>>>>
>>>>
>>>> On Mar 14, 2008, at 12:14 PM, Deepak Chandran wrote:
>>>>
>>>>     
>>>>       
>>>>> Hello standards group,
>>>>>
>>>>> From all the standards discussion, I think that there are two separate
>>>>> standards for parts. If this is the case, then it should be made 
>>>>> explicit.
>>>>>
>>>>> The first type of standard is for atomic parts (better word needed?)
>>>>> such as promoters, rbs, etc. (that cannot be broken down further). The
>>>>> "standards" for these parts is simply a list of characteristics. For
>>>>> example, a promoter would have its sequence and Jason-units as its
>>>>> characteristic feature. RBS would have sequence and some other units.
>>>>> The list of characteristic features are probably best if developed by
>>>>> experimentalists -- the question to ask is: what is it that makes this
>>>>> promoter unique?
>>>>> Sequence information is definitely needed for atomic parts.
>>>>>
>>>>> The second type of standard is for composite parts (better word?) such
>>>>> as iGEM projects. I do not think that the sequence for composite parts
>>>>> is needed -- if we know the atomic parts that make up this composite
>>>>> part, then we can easily determine the sequence. What is needed is the
>>>>> order in which the atomic parts are arranged on the plasmid and the
>>>>> circuit-diagram that explains the mechanism of the part. Someone should
>>>>> be able to take a composite parts and replace some of the atomic parts
>>>>> just like upgrading a computer by replacing the RAM.
>>>>>
>>>>> One can wonder whether things like protein domains or fusion proteins
>>>>> are atomic or composites. I think the question is whether the part is
>>>>> modular (i.e. whether it can be taken apart and reconstructed using
>>>>> slightly different components).
>>>>>
>>>>> In summary:
>>>>> A language is needed for composite parts.  (sequence not needed)
>>>>> A list of characteristics is needed for atomic parts. (sequence needed)
>>>>>
>>>>> If there is disagreement on this, please let me know why, so that I can
>>>>> eliminate my confusion. If there is agreement, then perhaps we should
>>>>> make this fact explicit and categorize our proposals to one of the two.
>>>>> We can make more directed progress that way.
>>>>>
>>>>> By the way, this categorization is not meant to disturb the
>>>>> part/device/system hierarchy.
>>>>>
>>>>> Ralf, I think that you language makes more sense if it is for composite
>>>>> parts, because you would need more descriptions for an atomic part. I
>>>>> will comment on that later.
>>>>>
>>>>> --Deepak
>>>>>
>>>>> _______________________________________________
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>>>>> Standards at biobricks.org
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>>>>>       
>>>>>         
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>>>   
>>>     
>>   
> 
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-- 
________________________________

Dr. Raik Gruenberg
http://www.raiks.de/contact.html
________________________________