Lina: a Laboratory Inventory System for Oligonucleotides, Microbial Strains, and Cell Lines Ahmed F

University of New Haven Digital Commons @ New Haven Electrical & Computer Engineering and Computer Electrical & Computer Engineering and Computer Science Faculty Publications Science

2011 Lina: A Laboratory Inventory System for Oligonucleotides, Microbial Strains, and Cell Lines Ahmed F. Yousef Masdar Institute of Science and Technology

Ibrahim Baggili University of New Haven, [email protected]

G. Bartlett Bartlett Consulting, Indianapolis

Michael D. Kane Purdue University

Joe S. Mymryk University of Western Ontario

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Publisher Citation Yousef, A. F., Baggili, I. M., Bartlett, G., Kane, M. D., & Mymryk, J. S. (2011). Lina: A laboratory inventory system for oligonucleotides, microbial strains, and cell lines. Journal of the Association for Laboratory Automation, 16(1), 82-89

Comments Dr. Baggili was appointed to the University of New Haven’s Elder Family Endowed Chair in 2015. Copyright (c) 2011 by the Society for Laboratory Automation and Screening. Software available at http://linasoft.weebly.com. See also http://publish.uwo.ca/~jmymryk/LINA.html Innovation Brief

LINA: A Laboratory Inventory System for Oligonucleotides, Microbial Strains, and Cell Lines

A.F. Yousef,1 I.M. Baggili,2 G. Bartlett,3 M.D. Kane,4 and J.S. Mymryk1* 1Department of Oncology and Microbiology & Immunology, University of Western Ontario, London, Ontario, Canada 2College of Information Technology, Zayed University, Abu Dhabi, UAE 3Bartlett Consulting, Indianapolis, IN 4Department of Computer and Information Technology, Purdue University, West Lafayette, IN

n this article, we present the Laboratory Inventory INTRODUCTION Keywords: Network Application (LINA), a software system that I Biomedical research has become ever more data biomedical systems, assists research laboratories in keeping track of their intensive.1 The rapid development of biological tech- laboratory collections of biologically relevant materials. This open nology has similarly resulted in the production of inventory, source application uses relational Microsoft Access new laboratory reagents, including DNA constructs, relational database database technology as a back end and a Microsoft .NET antibodies, and cell lines, at an exponential rate. application as a front end. Preconstructed table templates Generating and maintaining reagent records have are provided that contain standardized and customizable always been vital aspects of successfully running data fields. As new samples are added to the inventory, a research laboratory, and this was traditionally each is provided with a unique laboratory identifier, which organized using paper records. However, the days is assigned automatically and sequentially, allowing rapid when academic scientists could efﬁciently keep track retrieval when a given reagent is required. The LINA of all the reagents in their laboratory using a note- contains a number of useful search tools including book and pen have come to an end. The use of computer databases to maintain and a general search, which allows database searches using up access laboratory reagent records was the obvious to four user-defined criteria. The LINA represents an next step in the evolution of modern laboratory prac- easily implemented and useful organizational tool for tices. Indeed, many programs have been developed in biological laboratories with large numbers of strains, industry that are very useful in cataloging, and ac- clones, or other reagents. (JALA 2011;16:82–9) cessing records related to experiments performed and reagent inventories. These industry-produced programs include software such as the Cryotrack inventory management system (by Cryotrack, Ltd., *Correspondence: J. S. Mymryk, Ph.D., Department of Oncology Los Altos, CA), Inventory Workgroup (by Cam- and Microbiology & Immunology, University of Western Ontario, 790 Commissioners Road East, London, Ontario N6C 4L6, bridgeSoft, Cambridge, MA), LABCOLLECTOR Canada; Phone: þ1.519.685.8600, ext. 53012; Fax: (by Chemistry Software Ltd., Houston, TX), and ez- þ1.519.685.8616; E-mail: [email protected] Freezer (by ATGC labs, Frederick, MD). All these 2211-0682/$36.00 systems are comprehensive and allow scientists to or- Copyright c 2011 by the Society for Laboratory Automation and ganize their inventories efﬁciently. However, one Screening drawback to these software programs is the high cost doi:10.1016/j.jala.2009.07.004

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Figure 1. Screenshot of all four tables in the Laboratory Inventory Network Application. The four separate tables can be opened simultaneously and manipulated in individual windows. They can be tiled vertically, horizontally, and cascaded using the ‘‘Windows’’ pull-down menu.

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Table 1. Summary of the entries in the four tables that make up the Laboratory Inventory Network Application database

‘‘Oligonucleotides’’ table Description of entry Lab name This is assigned a sequential numerical designation automatically. Former name This is the name of the oligo before it was entered into the database. Date This is easily entered using a pop-up calendar. Purpose Indicates the intended use of the oligonucleotide. Sequence The nucleic acid sequence of the oligonucleotide is entered here. Length This is automatically generated as the sequence is entered. Restriction sites Any restriction site present in the sequence can be entered here. Gene The name of the gene for which the sequence anneals to. Species The species from which the target gene was derived from. Donor The person who designed or donated the oligonucleotide is entered here. Strand Top/bottom strand to which the oligonucleotide anneals to can be designated here. Position The location of annealing (e.g., 59 or 39 end, base pair X) can be entered here. Stock concentration The concentration of the laboratory stock can be entered here. Supplier The company from which the oligonucleotide was acquired. Comments Any additional comments can be inserted here. ‘‘Yeast’’ table Description of entry Lab name This is assigned a sequential numerical designation automatically. Former name This is the name of the strain before it was entered into the database. Date This is easily entered using a pop-up calendar. Plasmid Plasmids harbored by the yeast strain can be indicated in this ﬁeld. Genotype The yeast strain’s genotype can be entered here. Mating type Mat a or Mat alpha can be entered here. Donor The source of the yeast strain. Comments Any additional comments can be inserted here.

‘‘Bacteria’’ table Description of entry Lab name This is assigned a sequential numerical designation automatically. Former name This is the name of the strain/plasmid before it was entered into the database. Date This is easily entered using a pop-up calendar. Host strain The strain of the bacteria (e.g., DH5alpha) is entered here. Markers The antibiotic marker of the plasmid (e.g., ampicillin) is entered here. Plasmid size The size of the plasmid in basepairs can be entered here. Donor The person who constructed or donated the plasmid can be entered here. Parent vector The name of the backbone vector can be entered here. Insert The name of the gene inserted into the plasmid can be entered here. Comments Any additional comments can be inserted here.

‘‘Cell Line’’ table Description of entry Lab name This is assigned a sequential numerical designation automatically. Cell line name The American Tissue Culture Collection name can be entered here. Date This is easily entered using a pop-up calendar. Former name This is the name of the cell line before it was entered into the database. Source The person who created the cell line or the source can be entered here. Storage location Refers to what freezer and what box the vials are in. Preferred medium Refers to the appropriate tissue-culture medium required for growth. Number of vials available Refers to the number of vials left in the freezer. Species The species the cell line was derived from. Tissue type The kind of cell type/tissue was the cell line derived from. Modiﬁcation Refers to any plasmids integrated or other genetic modiﬁcations. Passage number Refers to how many times the cell line was passaged in culture. Comments Any additional comments can be inserted here.

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the ‘‘Design’’ view of Microsoft Access. One useful fea- 3. Search and Retrieve Entries. When conducting an experi- ture available for all of the tables is that a sequential ment, the laboratory member can search LINA for specific number is automatically generated each time a new entry reagents that are required. Each database table is searched is added. This feature allows for all the members of separately. Up to four fields can be searched simulta- a given lab to share these reagents as they are given neously using the Boolean operators AND/OR/NOT, a lab number as an identifier. Furthermore, a ‘‘com- allowing efficient searches in large inventories (Fig. 3). ments’’ entry is available for all the tables. This allows 4. Specialized Oligonucleotide Search Tool. A useful DNA for miscellaneous information including cryoagents used sequence tool was developed where the DNA sequence to store the sample, and details pertaining to the con- for an entire gene or genomic cluster can be entered, struction of the reagent. More information regarding and the user’s oligonucleotide table is subsequently the LINA tool is available on the LINA web sites, which searched for matching sequences. The matches can be are listed under the ‘‘distribution and availability’’ sec- direct, complimentary, or reverse complimentary to the tion that follows. DNA sequence entered. The output of the search dis- 2. Create, Update, and Delete Entries. This function is avail- plays the regions of the gene that match the given oligo able for each of the four database tables. Each entry can and a color-coded designation corresponding to the type be edited by double-clicking the entry on the master list, of match (Fig. 4). or selecting edit from the pull-down menu, and modify- 5. Generate and Print Reports. The master list for each table ing data fields as necessary. Entries can be deleted via along with all search results can be printed to a text file a right-click pop-up menu. New entries can be added (TXT) and subsequently printed to hard copy. Further- by either a right-click pop-up menu or a pull-down menu more, each entry in a table can be selected individually that is available for each table. Another convenient fea- for printing in a similar manner. Lists can be printed ture added to every table is the availability of two addi- by selecting ‘‘print list’’ from the pull-down menu. This tional customizable fields. These can be configured in will also generate a text file. Individual entries can be the master settings menu of the software program for printed by a menu that appears when you right click each database table (Fig. 2). Although it is not possible the desired entry in the list. This option is particularly to list all the possibilities that these two extra fields might useful should a reagent be donated to another labora- represent, examples might include rack number for the tory, in that a ready-made ‘‘specification-sheet’’ contain- bacterial stocks, and expiry date if applicable. Neverthe- ing all pertinent data relevant to the reagent is readily less, these customizable fields should facilitate the adap- available to accompany the shipment. tation of this system to a wider range of laboratories than originally intended. HARDWARE AND SOFTWARE SPECIFICATIONS

The LINA system was intentionally designed to be straight- forward to rapidly facilitate its implementation and

Figure 2. Screenshot of the settings menu for Laboratory Inven- tory Network Application. Each individual table can be enabled, and up to two custom fields can be added to each table. Further- more, specific NaCl and formamide concentrations can be entered to calculate the melting temperatures of the oligonucleo- Figure 3. Screenshot of the search tool available for each table in tides in the ‘‘Oligo table.’’ Finally, the location of the database file Laboratory Inventory Network Application. Up to four indepen- (*.mdb) is also determined in this menu, which allows for different dent fields can be searched simultaneously using the AND/OR machines to point to the same file. Boolean operators.

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separate databases were used, thus four separate MDB files were necessary. The new software integrated all four MDB files into one and allowed for a user-friendly interface with vastly superior search functions. The program underwent 12 months of beta testing in the laboratory, and was used by 10 members. Through the beta testing, nine different ver- sions were created, with LINA version 0.9 finally satisfying the suggestions that the testers provided.

Usability and Assessment To date, there are 3359 entries in the ‘‘bacteria’’ table, 327 entries in the ‘‘yeast’’ table, 802 entries in the ‘‘oligo’’ table, and 222 entries in the ‘‘cell line’’ table in the LINA database maintained by the authors’ laboratory. Entries were successfully retrieved using the search tools available for each table. Furthermore, appropriate oligonucleotides were identified to sequence various DNA constructs using the PCR search tool available in the ‘‘Oligo’’ table. Finally, the testers also did not notice any issues with regard to any aspect of the software performance as the number of entries increased from several hundred to several thousand. The tool has become indispens- Figure 4. The oligonucleotide front end contains an additional able for the daily operations of the research laboratory where ‘‘DNA Bind Search,’’ which allows the user to search for identical, it was developed. The changes made to the tool as testing was complimentary, reverse, or reverse complimentary matches to done have resulted in a product that is found to be user a given sequence. (A) Screenshot of the search tool, which allows the user to enter a nucleotide sequence and specify the minimum length the match has to be. (B) The ‘‘DNA compare’’ function allows the user to see exactly where in the entered sequence an oligonucleotide binds. In this screenshot, the oligonucleotide JMO-0004 binds in a reverse complimentary way, denoted by the gray shading, to the entered sequence. distribution. The structure for all four database tables is organized in a single Microsoft Access (MDB) file. The file is accessed and modified by an executable (EXE) file that was developed using Visual Basic .NET. Therefore, the basic technology requirement for running LINA is a computer with an operating system that can run the .NET framework. The system can set up to be used in two ways (Fig. 5). In the first example, all the data are kept on one computer (Fig. 5A). This is ideal when there is only one laboratory computer, which is shared by different users. In the second case, a central file server hosts the MDB file. In this scenario, multiple computers that run the executable file (.exe) can use LINA simultaneously (Fig. 5B). In this case, each user on their unique computer would configure the master settings menu to point to the MDB file on the common file server using the settings menu (Fig. 2). This allows the whole laboratory’s inventory to be stored as one common database, making it easier for different Figure 5. Schematic representation of two ways to set up members of the lab to access reagents. Laboratory Inventory Network Application in the laboratory. (A) Different people in the laboratory could maintain their own records simply by running the program on their personal com- Testing puters (PCs) and pointing to a database file located on their PC. The software was introduced for testing in March 2007. (B) Alternatively, a single database can be used for all the members The previous system used was a Microsoft Access database in a laboratory by having different PCs running the executable pro- that could search single fields at a time. Furthermore four gram file and pointing to a database file on a network server.

86 JALA February 2011 'RZQORDGHGIURPMODVDJHSXEFRPDW81,92)1(:+$9(1/,%5$5Linux. Mono is also com- demonstrated that small samples (n ¼ 10e12 users) yield re- patible with the Macintosh operating system. Adaptation liable results.4 Taken together, the SUS is a reliable method of LINA to the Mono platform may allow the execution for conducting a usability test of new software. of LINA under different operating systems including The usability of the LINA program was assessed by admin- Mac OS and Linux. istering an SUS questionnaire to 10 participants (Table 2), all of whom worked in the same laboratory. These 10 partici- To test the portability of the LINA application to the pants did not include any of the authors. The average SUS Mono environment, the Mono Migration Analyzer score was 86.25 with a standard deviation of 3.95. This SUS (MoMA) tool was used. The LINA assembly was tested score is comparable or superior to another published access- to see how portable the application would be against based application, Microsoft Excel, and the commonly used Mono version 2.4. The results indicated that with modest operating system Windows XP.5e7 It is generally accepted that changes to the assembly, LINA could become easily por- the applications with an SUS score of 50 or above are consid- table, allowing it to be deployed on operating systems ered user friendly.7 The LINA program is therefore a system other than Microsoft Windows in conjunction with that does not require a lot of training, is easily implemented, Mono. The results from running MoMA on the current and is generally quite user friendly. version of LINA are displayed in Figure 6A, B. All the methods that were used while programming LINA do exist in Mono (Fig. 6A). However, the P/Invokes methods FUTURE RECOMMENDATIONS used when saving the application’s configuration files do The LINA project has successfully achieved all of its original not exist under the Mono environment. An additional objectives. The newest version is stable and has been background color change from the RichTextBox control also triggered a portability problem shown in the ‘‘Methods called marked with MonoTodo’’ (Fig. 6B). If Table 2. System Usability Scale was administered to 10 members the seven method calls were to be changed to methods of the laboratory who used the program that are supported by the Mono environment, then the LINA application should be portable to any operating Lab member Score system that can run the Mono platform. As LINA is an 1 87.5 open source application, users that are interested in using 2 92.5 LINA on other operating systems have the ability to port 390the application to their preferred operating system by 485addressing the issues highlighted in Figure 6. 590 6 87.5 2. Barcoding. As the number of reagents increase, manual 7 82.5 sorting becomes more cumbersome and approaches the 880impossible. The ability of LINA to assign and print 9 82.5 barcodes is a definite possible improvement if users sug- 10 85 gest it. Barcoding is already available in other industry- Average 86.25 developed laboratory management systems. Standard deviation 3.952847075 3. Expanding the Types of Tables Available. More tables can be added including animal, virus, antibody, and chemical

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LINA.html or http://linasoft.weebly.com. There are detailed instructions on these web sites regarding downloading and first time use of the application. Two files will be needed for the initial install: the application file and the empty database file. Subsequent installations only need the application file if LINA is to be used in a network (Fig. 5B). Further- more, the open source code for LINA is also available for download from both sites.

CONCLUSIONS

The LINA system is a free software that allows academic laboratories to efficiently manage their inventory of specialized molecular biology reagents. The software system can be set up to work on one computer or in a network with multiple users. The features provided by LINA are comparable to the features available in many commercially available database programs. These features include a versatile search function where entries in even large tables can be efficiently located by searching up to four data fields simultaneously. The automatic generation of stock numbers (or a lab number in LINA) is another example of these commercially available features. Furthermore, a useful DNA se- Figure 6. Results obtained from analyzing the Laboratory Inven- quence search tool was developed specifically for the tory Network Application (LINA) assembly using Mono Migration oligonucleotide table, which is not available on any of the Analyzer. (A) Screenshot of the analysis summary indicating that commercially available software. Evaluation of the system’s there are seven issues that need to be resolved to for LINA to usability was carried out using the SUS tool where it be compatible with Mono. (B) Screenshot of the detailed report yielded an average score of 86.25 with a standard deviation highlighting the issues that need to be resolved for LINA to be of 3.95 (n ¼ 10). compatible with Mono. The final application available for download is a stable product that has many advantages over Microsoft Excel, inventories. The four tables used in this implementation which is currently the most common method of keeping are ideal for laboratories that do molecular biology work track of laboratory reagents by computer. The search tool, in yeast and mammalian tissue culture, but may not be along with the specialized search tool available for the sufficient for the needs of laboratories that conduct ‘‘Oligonucleotide’’ database, is far more useful than the research that uses custom-made chemicals and molecules, basic search function in Excel. Furthermore, the ability to and laboratories that work with transgenic animals. print specific search results, as well as automatically gener- 4. Security. There were no technical security measures ate and assign identifier numbers are more examples of taken into account when designing LINA because the why LINA is superior to Excel for keeping track of labora- focus was to rapidly develop the software and test usabil- tory reagents. Finally, it is worth noting that the develop- ity. The data were not encrypted because the researchers ment of this system highlights the rewards that can be felt the need to be able to view the data in clear text in the achieved when trans-disciplinary collaboration is used to table fields when viewing the .mdb file. Nevertheless, solve problems. a feasible addition to the LINA software would be an authorization function in which LINA users would be asked to add a username and password. The details of ACKNOWLEDGMENTS the user session including what changes or additions were The authors would like to thank all the beta testers for their valuable input. made to each table could also be logged in this case. AFY was supported by an Ontario Graduate Scholarship, and a CIHR strategic training program in cancer research and technology transfer PhD student award. DISTRIBUTION AND AVAILABILITY Competing Interests Statement: The authors certify that they have no relevant The intent behind developing LINA was always to provide financial interests in this manuscript. a free database maintenance application for academic laboratories. It was determined that the most efficient way to dis- REFERENCES tribute the program is through a LINA homepage on the 1. Reichhardt, T. It’s sink or swim as a tidal wave of data approaches. World Wide Web at http://publish.uwo.ca/wjmymryk/ Nature 1999, 399, 517e520.

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