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Technical Note
OptoBase: A web platform for molecular optogenetics Katja Kolar, Christian Knobloch, Hendrik Stork, Matej Žnidari#, and Wilfried Weber ACS Synth. Biol., Just Accepted Manuscript • DOI: 10.1021/acssynbio.8b00120 • Publication Date (Web): 18 Jun 2018 Downloaded from http://pubs.acs.org on June 19, 2018
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ACS Synthetic Biology
OptoBase: A web platform for molecular optogenetics. Katja Kolar1,2, Christian Knobloch3, Hendrik Stork1, Matej Žnidarič4, Wilfried Weber1,2* 1
Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany BIOSS - Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany 3 Faculty of Engineering, University of Freiburg, 79110 Freiburg, Germany 4 Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland 2
Abstract OptoBase is an online platform for molecular optogenetics. At its core is a hand-annotated and ontology-supported database that aims to cover all existing optogenetic switches and publications, which is further complemented with a collection of convenient optogenetics-related web tools. OptoBase is meant for both expert optogeneticists, to easily keep track of the field, as well as for all researchers who find optogenetics inviting as a powerful tool to address their biological questions of interest. It is available at https://www.optobase.org. This work also presents OptoBase-based analysis of the trends in molecular optogenetics.
Keywords: database, optogenetic tools, optogenetics, photoreceptors, protein switches, synthetic biology
OptoBase Optogenetics is a rapidly emerging discipline, where naturally occurring light-responsive proteins are engineered into genetically encoded protein switches, which can be utilized to control cellular signaling and behavior in an unprecedented space- and time-resolved manner. Thanks to these powerful characteristics, optogenetic tools enable us to systematically dissect or direct select biological processes, and thereby gain a deeper understanding of the cellular inner workings. Moreover, they also hold a potential for further development into biomedical and other applications. To provide a means for thoroughly keeping track of the diverse and fast-growing pool of available optogenetic tools and applications on the one hand, and a comprehensive source of essential information for the researchers who are new to the field on the other, we have established OptoBase, an online platform for molecular optogenetics (i.e. non-ion channel-based optogenetics as used in neurobiology). OptoBase comprises an advanced database of optogenetic switches and publications, and a collection of useful web tools and other resources for optogenetics (Figure 1a).
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For quality assurance, all its content, including that contributed by the users (Figure 1b), is curated by the OptoBase team, and reviewed to confirm its accuracy and relevance. Last but not least, establishing OptoBase has enabled us to analyze the trends in the field of optogenetics, which are presented in the last section of this work. a)
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c) Light color
Publication search Optogenetic switches Individual switch
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search by the host cell line or organism of a designed optogenetic system
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search by the type of biological application of an optogenetic system
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Materials Units converter Field Statistics About & FAQ
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Aa Add a new glossary term
Send us a comment, critique or suggestion
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search by an optogenetic switch
Host name
Find the expert Find the switch
search by the color of a switch-inducing light
Multichromatic
search for review papers
search for papers that benchmark different optogenetic switches search for basic research papers on photoreceptors search for papers that combine multiple optogenetic switches within a single optogenetic system
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Figure 1: Content of OptoBase.org. a) Architecture of the OptoBase platform. b) Submission menu enables the community to contribute to OptoBase content, and thereby help the OptoBase team comaintain the platform up to date. c) Each publication in the OptoBase database is manually assigned a set of ontology-supported tags that enable content-based searching. d) An example of an optogenetics publication as viewed in the Publication Search results. The line of colored tags provides quick and precise information on the nature of the presented optogenetic system(s): blue tag – light color used for stimulation of the optogenetic switch, grey tag – name of the optogenetic switch, green tag – host cell line (or alternatively an organism) of the designed optogenetic system, teal tag – type of biological application achieved through optogenetic control. e) OptoBase homepage offers an overview of the available switches and access to the information pages of each of them.
Publication Search The first main feature of OptoBase is a manually curated database of optogenetic and related publications, which can be searched in a highly precise and efficient manner via content-based tags (https://www.optobase.org/search). To this end, each publication in the database is systematically analyzed and hand-assigned a set of searchable tags describing its content (Figure 1c). This provides the possibility to extract publications involving a specific trait, such as a particular optogenetic switch or a host organism, by using an OptoBase-specific syntax (as exemplified in Figure 1d). To further improve the search quality, all tags are organized within an ontology, a structure that describes their relations as well as common synonyms. The advantage of an ontology-supported search, such as the one from OptoBase, is that it overcomes the semantic gap between the tags assigned to the publications and the keywords in the query syntax. For instance, searching for host:”mammalian” will return all publications tagged as describing optogenetic systems implemented in any mammalian cell line or mammal (whole organism), while host:”CHO-K1” will return publications that describe implementations in this cell line specifically. Furthermore, searching for host:”CHOK1” or host:”CHO K1” will recognize the two entries as synonyms of host:”CHO-K1”, and thus return the same result as the latter query.
Optogenetic Switches The next main feature of OptoBase is the first comprehensive database of existing (currently 45) optogenetic switches (https://www.optobase.org/switches), which aims to provide an immediate access to useful and well-structured information on them (Figure 1e). Switches are organized according to the photoreceptor classes that they belong to, and each have their own subpage. There, one can find a scheme that illustrates the mode of action of a particular switch, a table of essential characteristics, its interactive, Protein Data Bank-linked 3D structure, and the list of all original research publications where the switch has been implemented.
Tools Find the Expert. This is a search engine where one can enter a scientific query and as a result obtain a ranked list of authors with the most original research publications matching the query. Each author name is presented together with the number and a condensed list of the matching publications, which can be instantly also viewed in detail. As such, this tool serves to identify the scientists with the most hands-on experience in a particular aspect of optogenetics, and thus find a potential new collaborator or help from an expert. (https://www.optobase.org/fte)
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Find the Switch. What optogenetic switch to choose for the development of a new optogenetic tool highly depends on the kind of the application that one wants to establish, as well as on the host cell line or organism, i.e., where the application will be implemented. Find the Switch tool was established to help scientists systematically navigate themselves in the diverse multitude of existing optogenetic switches. The tool lets a user choose among various filter options to thereby describe the requirements that they have for their upcoming optogenetics project, and as a result returns a list of matching optogenetic switch candidates. (https://www.optobase.org/fts) Find the Application. This tool enables one to discover original research publications that present a certain kind of biological application(s) achieved through optogenetic control, such as optogenetic control of endogenous gene expression. To this end, a user defines a custom filter by selecting their criteria from a comprehensive list of OptoBase-defined topics for description of biological applications, and choosing between the OR and AND logical operators to combine them. (https://www.optobase.org/fta) Materials. This is a structured collection of links to various convenient material sources for optogenetic experiments. It is meant to cover the learning material that explains the basic concepts of optogenetics, sources where one can obtain readily available plasmids bearing optogenetic genes, directions on how to construct and/or program illumination devices, as well as useful protocols on how to set up optogenetic experiments. (https://www.optobase.org/materials) Illumination Units Converter. Data about the light intensity used to control an optogenetic system is in publications oftentimes provided in different units, which makes it difficult for one to grasp the information. Illumination Units Converter allows to quickly convert different commonly used scales of irradiance to photon flux, and vice versa. (https://www.optobase.org/converter)
Trends in optogenetics Analysis of the OptoBase database showed that the field of molecular optogenetics has been growing exponentially (with the doubling time of 2 years, since 2011) ever since its beginning in the early 2000s (Figure 2a). As of April 2018, there were 298 research publications and 98 reviews. Most of the former (198) describe optogenetic systems implemented in mammalian host cell lines or whole organisms. This reflects the superior potential of optogenetics as a means for answering research questions in complex biological contexts (Figure 2b). Likewise, as many as 22% of the research publications present optogenetic systems implemented in vivo, and not only in single cells (Figure 2c). The generic applicability of optogenetics is further underlined by the increasingly growing number of host cell lines and organisms in which optogenetic systems have been implemented (Figure 2d). Versatility of optogenetics can be also observed from the many different kinds of biological applications of optogenetic tools (Figure 2e). As evident from the OptoBase classification of biological applications, the largest fraction of publications presents the applications for light-control of cytoskeleton, cell shape or cell motility (Figure 2e, in green). Besides, there exist numerous publications whose scope is rather development or characterization of new optogenetic tools (Figure 2e, in grey).
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a) Optogenetics publications
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Endogenous gene expression Transgene expression Nucleic acid editing Epigenetic modification Organelle manipulation Control of vesicular transport Control of cytoskeleton / cell motility / cell shape Signaling cascade control Immediate control of second messengers Cell cycle control Cell death Cell differentiation Developmental processes Neuronal activity control Control of cell-cell / cell-material interactions Focus on tool development/characterization
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Figure 2: Trends in molecular optogenetics. a) Cumulative number of original research and review publications on molecular optogenetics. b) Cumulative number of the original research publications which present optogenetic systems implemented in individual types of host cell lines or organisms. c) Cumulative number of the original research publications which present optogenetic systems implemented in individual animals. d) Cumulative number of different host cell lines and whole organisms in which optogenetic systems have been already implemented. e) Distribution of original research publications according to the type of biological applications, achieved through optogenetic control (as of April 2018). In conclusion, we would like to establish OptoBase as the collaborative hub for the exciting and perspective field of optogenetics, which will bring together the scientists who develop optogenetic tools and those who use them as a means for answering complex biological questions, and thus promote cross-disciplinary science.
Author Information Corresponding Author *E-mail:
[email protected] Notes The authors declare no competing financial interest.
Acknowledgement We would like to thank Barbara di Ventura and the Weber group, especially Hanna Wagner, for helpful discussions and comments regarding the platform content. This work was supported by Excellence Initiative of the German Federal and State Governments (BIOSS-EXC-294).
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