Team:METU Turkey Software

From 2010.igem.org

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<h2>Database Standardization</h2>
<h2>Database Standardization</h2>

Revision as of 21:57, 26 October 2010

Team

METU Turkey Software is an interdisciplinary team of 8 students and 3 advisors from various backgrounds such as Molecular Biology, Bioinformatics, Computer Engineering and Computer Education and Instructional Technology. We have put our knowledge and experience in our fields together to bring a much needed solution to a daily problem in field of synthetic biology for iGEM 2010

Motivation

Since 2008, we have been participating in iGEM as METU ( Middle East Technical University) wet-lab team, and each year we have noticed the increasing number of teams participating, along with an increase in biobricks entries at partsregistry.org. While having more choices of biobricks to choose from is incredible, searching for and choosing the appropriate parts is becoming a challenge. This year during the construction process of iGEM biobrick parts for our new project, we felt the need for an application to find interacting parts based on an input/output model to design the genetic constructs. Using a specialized software for searching the parts registry to find possible biobricks to include into our construct would be much easy, fast and accurate than manual. We have shared our need with a group of friends who are software engineers, and initiated the METU_Turkey_SOFTWARE team where we worked together over this summer to build the BIO-Guide software.

Scope and Future Aspects

The partsregistry.org is a continuously growing collection of standard genetic parts that can be mixed and matched to build synthetic biology devices and systems. The Registry is based on the principle of "get some, give some". Registry users benefit from using the parts and information available in the Registry for designing their own genetically engineered biological systems. In exchange, the expectation is that Registry users will contribute back to the information and the data on existing parts and will submit new parts they have designed in order to improve this community resource.

As an expanding database partsregistry.org needs to be more organized and the standardization template needs to be improved. Additionally, the potential of multiple ways of using each part in different construct combination brings out the necessity for an application to search through the database. BIO-Guide is the first designed software that organizes over 1000 parts in partsregistry.org as possible atomics parts to build new biological device and systems for specific input and outputs based on graph theory. The requirement of similar applications and software tools are now inevitable in the emerging field of synthetic biology. The innovative approach that makes the partsregistry.org easy to use for synthetic biology applications is the collection of standardized parts that can be used in any combination with minimal effort under one database. But while working on our algorithm to search for possible combinations of parts depending on the given input and output, we have realized that present standards are inadequate and parts registry form must be improved.

In very near future a new format for parts registry form is needed and few additional features should be implemented to have more control on the database. We are planning to suggest a new format and features for the parts registry based on the survey results we have received. And planning to build the next version of BIO-guide based on the revised parts registry form. Along with using new parts registry standards we will be improving the algorithm, so that the software can search through more complex relations and returns all possible functional constructs.

Project Introduction

As the field of Synthetic Biology is on the rise, iGEM is growing up very fast and the number of parts in the parts registry is increasing with the addition of more complex parts each day. After facing some difficulty while running our algorithms on the parts registry, the need for more effective standardization of parts entry was apparent. We have investigated the information on parts in iGEM’s 2010 distribution and reorganized the information on the parts registry forms according to the needs of our algorithm. Then we have used graph theoretic modeling to visualize the relations between iGEM Parts and to standardize the representation of the parts as much as possible by graph theoretical methods. This helped us to find input output relations between the parts. Furthermore, our program BIO-Guide is now able to provide alternative pathways to construct the most reliable and functional Biobrick devices with respect to given inputs and expected outputs as a guide to Biobricks parts registry.

Notebook
Download
Misc - Collaboration
Design
Code
Human Practices
Material
User Guide
Safety

Methods

Part Extraction Standards

All information about the parts that are essential in experimental setup of iGEM projects has been utilized. The information for the parts available provided with all three 384 well plates in Spring 2010 distribution have been standardized. Our standardization criteria have been discussed in detail under Database Standardization. ER diagram has been generated which simply describes the organization of the data. Around 70% of the parts information has been fetched by the custom parsing code from XML and Excel files provided by iGEM. Rest of the data had to be collected and organized manually as the organization of these data cannot be standardized to generate an algorithm. This step was one of the most time consuming steps in our project. For each construct and Biobrick the information collected was; Activity, Inducer, Activator, Repressor and Inhibitor for promoters and Inducer, Activator, Repressor and Inhibitor information valid for synthesized molecules (mostly proteins and RNA fragments etc.)

Combination

Rules (Image Combinations) In order to build our input/output relations graphs first we run our algorithm on the real combination dataset which contains all few thousand different possible combinations of the biobricks. But after performing all combinations for the first few hundred biobricks application’s rate slowed downed tremendously, which also become very time consuming for displaying biobricks graphs. To overcome this bottleneck we have developed a new strategy, where we have only used the construct combinations of the biobricks distributed within the plates. Moreover, according to information gathered from the subparts of the constructs distrubuted, we also collected the subpart assembly order, such as 1st: promoter, 2nd:rbs, 3rd:coding seq, any internal parts and the Last: terminator. Each specific Biobrick type has been assigned a number as a unique image ID from 1 to 19. Gathering the information on subparts was not a direct forward process. ImageID assembly orders for each construct has been used to extract the type information for each subpart with that construct. This innovative approach helped us to reveal 400 possible brick combinations present within the 3x384 well plates distributed by iGEM in Spring 2010.

Support
Future Plan

Database Standardization

Two main focuses of our project was the organization of the available information about Biobricks on iGEM’s website and development of a software application to help synthetic biologists at the experimental set-up level by providing all available construct combinations for any given input and output relations ,which they can utilize for their own project.

Normalization and re-organization of the part information at iGEM’s web site was needed in order to develop our application, which will automatically search the possible construct combinations. For the organization and analysis of the Biobricks, we used part info for Spring 2010 distribution. The information on all three 384 well plates distributed by iGEM scrutinized and checked individually to specify the standards available and needed. iGEM is providing so many parts within a hierarchical way, but there is no order in the information flow and no common standards. Furthermore, the information bulk is being used in an ineffective manner. Some of the parts distributed are known to be nonfunctional. Web pages for parts contain lots of information, but majority of them, are again not ordered. Moreover, some additional information had to be removed or replaced in such a way that the information for parts can be used effectively. And removal of the redundant bulk information related with parts at iGEM’s web site had been recommended for future.

Although, the final standardization, which we have suggested is not for general public use and it was urgently needed in order to satisfy the needs of our algorithm. But, still it will be a valuable resource, since it summarizes the basic information about the parts.

As the first step to build the proposed standardization template, the headings selected related to parts are listed on Table 1. Submission of part IDs for individual parts is an accepted and quite valuable way of tracking information. Although, every part has unique partID, for every part there is a need to assign unique part names as official iGEM names. Part names will have an important role as they will be providing the short description about the part, which synthetic biologists can immediately recognize and utilize during the construction of unique Biobricks. Additionally unique part names will be helpful to identify the devices with more than one Biobrick in their constructs. Assignment of unique and distinct names for parts describing their nature and content will be helpful to researchers for the recognition of and search for the parts.

Headings Selected From Previous Entry Forms for Indication of Standardized Information

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PartID:

PartName:

Bricks:

BrickIDs:

ImageIDs:

RFC10:

RFC21:

RFC23:

RFC25:

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Table 1: The table above basically describes and designates qualities of parts which identifies their compositions and demonstrates the status of previously assigned standards. PartID refers to the unique ID number for parts including atomic parts and assemblies. PartName refers to the given unique names to parts. Bricks, refers to the shortcut names which specifies atomic parts. ImageIDs, refers to individual or combination of numbers that are assigned by us. RFCs refers to the states of parts based on RFC standards.

iGEM both provides individual, atomic parts and pre-combined constructs such as devices and systems. Availability of combined constructs is important to the researchers as combining individual bio-bricks one at a time will be very time consuming. These previously merged constructs, serve as the repository for puzzle and they can be used for different purposes. Up to date the largest and most trustworthy source, for synthetic biology and its components, is iGEM’s parts registry. In 2010, iGEM provided over 1000 parts that have initiated many projects. Having more atomic parts available in the iGEM’s repository, will lead to the design of more complex and robust constructs, and we would have a better chance to design different constructs for unique purposes. Also, for the parts that are already available, extra steps needs to be taken for the quality control and surveillance of these products. The quality control of the information for the parts is essential for the future of iGEM and synthetic biology. Even though we have found pre-determined RFC standards useful and included those to our standardized template, some individual parts still requires re-organization of the information as RFC standards alone for the functionality of parts, does not satisfy the needs for wet lab biologists.

Without a question there is an urgent need to build a distinct and specific database well organized with its own standards for synthetic biology; however, development of such a database is not an easy task.

Contact Information of Part Owners and Qualitative Group Comments about Parts

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Designers: Mail:

GroupFavorite:

StarRating:

Parameters:

Table 2: The above table simply depicts information about possessors of parts and their contact information and the popularity of the parts for groups. Parameters heading, refers distinctive experimental details unique to the usage of parts which should be decided by groups.

Second step for building the standardized template was to get the phylogenic information about the parts development process which includes the name of the group, designer and contact information, along with the comments from the group on the parts they have submitted. Contact information is especially important for iGEM as other groups who need extra information about the available part can reach to the required information. Even though contacting with the designers of the individual parts which are available is highly encouraged by iGEM, unavailability of contact information points at out the fact that iGEM’s parts registry needs strong re-organization in order to serve to the synthetic biology community properly.

Additionally, the “group favorite” and “starRating” fields are also important for individual evaluation of the parts, which doesn’t get the deserved attention from the iGEM groups. “Group Favorite” defines the confidence on the part by the designer group. “StarRating” defines the related part in terms of popularity and usage efficiency among the groups. According to our observations, most groups are not aware of either of the fields or they are used incorrectly or ineffectively. For example for a part with a full reporter which is known to be functional and gives precise and expected results the StarRating should be at least 2 stars, but for most of the parts in 2010 distribution, it is very difficult to observe a part whose “StarRating” is above one. For quick determination of functionality of the parts these two evaluations are important so they have been included in the proposed standardization template. But, as they were not properly used up to now for the re-organization of the parts information during the development of our software application we had to include all parts to our queries regardless of their evaluations based on “Group Favorites” and “ StarRatings”

Contact
Results
Results
Results