Team:Johns Hopkins-Software/theSoftware overview

We recognized a need for a comprehensive piece of software that provided the means to achieve an easier Plasmid Design process. Manual annotation is simply too time consuming, tedious, and error-prone. We wanted to create something to fix this noticeable setback of existing synthetic biology software. AutoGene sets a new technological standard by bringing automation to the plasmid design process. That being said, we developed a list of specific goals we wished to achieve. We split these goals into two modules, and decided the first set of goals would be achieved by AutoPlasmid, the second set of goals would be achieved by AutoDesign, and together, we would create AutoGene.

Each of these goals encompasses an extensive list of sub-goals. Here, we discuss the more detailed goals for our primary milestones listed above.

AutoPlasmid

AutoPlasmid was developed to take the process of annotating a plasmid to a whole new level. Firstly, we wanted to create a centralized depot of many thousands of well-known features and their associated sequences. We chose what we thought were some of the more popular features, and relied on databases such as SGD, PlasMapper, and the University of Wisconsin Madison. We aggregated over 40,000 features and compiled them into a complex database with the following tables:
1. Annotation
2. Feature
3. FeatureType
4. Oligo
5. Organism
6. Pathogen
7. Plasmid
8. RegistryPart
9. RegistryType

But we knew this database would grow as large as it did. To address this concern, we implemented Cloud Computing, what we feel is one of the most impressive aspects of our software application. A plasmid such as puc18 normally takes 4 hours on a slow computer to annotate and search through all our features. But in the cloud, with 30 parallel processes running at once, we can split up the algorithm and divvy up the work, resulting in a run of just 68 seconds, a dramatic decrease in time by 210-fold!

But we added many, many more features on top of this architectural backend. In particular, we gave users the ability to annotate their plasmid using imperfect matches selecting any threshold they want (ex. 95% match). While this significantly increases the time a particular annotation takes, it still results in rapidly fast annotations when the Cloud is used. In addition, users may select particular features they want to search for, such as Genes, Promoters, Terminators, and more. Lastly, users may translate DNA into amino acid in all 6 reading frames.

Once a plasmid is fully annotated, the user can do even more. They can look inside the plasmid, view details about each feature that was annotated, and manipulate the plasmid even more. They can add custom annotations, view where a particular segment of DNA is, and even isolate out features to later design with. Users can view oligo matches, and amino acid translation of particular DNA segments. One of the most useful features of the AutoPlasmid's plasmid view window is that a user can find exactly why a annotation was identified as an imperfect match. In puc18, it is well known that the origin has a 1 base pair mutation, for example. This can be easily located by viewing the details of the alignment.

Lastly, a user may export their annotated plasmid in any format they'd like: genbank, fasta, or SBOL. These standardized file formats are useful when using AutoGene in collaboration with other standard softwares, such as Ape. Our genbank format, in particular, preserves characteristics of annotations that may be crossed over to Ape, such as the color of each annotation.

***NOTE: scroll down below for examples images showing screenshots of all the aforementioned features.

AutoPlasmid is a simple-to-use annotation tool. Hand it a sequence of DNA, however big or small you'd like. Import a file or copy and paste the sequence.



Then sit back and watch. AutoPlasmid will search through a database containing 40,000 features and look for matches. Not only does it find perfect matches, but if you specify, you can search for imperfect matches with any threshold you'd like (ex. 90% match).



After searching for annotations, open your plasmid to look inside.



Interact with it by selecting features, manipulating the DNA, and adding any custom annotations you'd like. You can even view amino acid translations or oligo matches.







Lastly, you can view the details of an imperfect match.



AutoPlasmid is also compatible with a variety of standard biology tools, such as Ape. A plasmid can be imported as a fasta, gb, and SBOL file, as well as being exported as a fasta, gb, or SBOL file.

AutoDesign

AutoDesign takes the automation process to the next level. Using the annotated features that AutoPlasmid finds, the user may select features to design a new plasmid with. First, the user chooses features and drags them into the private registry.



Next, the user drags features into the private registry. The user can change the order of features, invert features, duplicate features, and delete features. At the same time, the user sees an updated version of the plasmid they are designing and the associated DNA.