Journal:FluxCTTX: A LIMS-based tool for management and analysis of cytotoxicity assays data
| Full article title | FluxCTTX: A LIMS-based tool for management and analysis of cytotoxicity assays data |
|---|---|
| Journal | BMC Bioinformatics |
| Author(s) |
Faria-Campos, Alessandra C.; Balottin, Luciene B.; Zuin, Gianlucca; Garcia, Vinicius; Batista, Paulo H.S.; Granjeiro, José M.; Campos, Sérgio V.A. |
| Author affiliation(s) | Universidade Federal de Minas Gerais, INMETRO |
| Primary contact | Email: alessa at dcc dot ufmg dot br |
| Year published | 2015 |
| Volume and issue | 16(Suppl 19) |
| Page(s) | 58 |
| DOI | 10.1186/1471-2105-16-S19-S8 |
| ISSN | 1471-2105 |
| Distribution license | Creative Commons Attribution 4.0 International |
| Website | https://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-16-S19-S8 |
| Download | https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/1471-2105-16-S19-S8 (PDF) |
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Abstract
Background: Cytotoxicity assays have been used by researchers to screen for cytotoxicity in compound libraries. Researchers can either look for cytotoxic compounds or screen "hits" from initial high-throughput drug screens for unwanted cytotoxic effects before investing in their development as a pharmaceutical. These assays may be used as an alternative to animal experimentation and are becoming increasingly important in modern laboratories. However, the execution of these assays in large-scale and different laboratories requires, among other things, the management of protocols, reagents, and cell lines used, as well as the data produced, which can be a challenge. The management of all this information is greatly improved by the utilization of computational tools to save time and guarantee quality. However, a tool that performs this task designed specifically for cytotoxicity assays is not yet available.
Results: In this work, we have used a workflow based LIMS — the Flux system — and the Together Workflow Editor as a framework to develop FluxCTTX, a tool for management of data from cytotoxicity assays performed at different laboratories. The main work is the development of a workflow, which represents all stages of the assay and has been developed and uploaded in Flux. This workflow models the activities of cytotoxicity assays performed as described in the OECD 129 Guidance Document.
Conclusions: FluxCTTX presents a solution for the management of the data produced by cytotoxicity assays performed at interlaboratory comparisons. Its adoption will contribute to guarantee the quality of activities in the process of cytotoxicity tests and enforce the use of good laboratory practices (GLP). Furthermore, the workflow developed is complete and can be adapted to other contexts and different tests for management of other types of data.
Keywords: laboratory information management systems, workflow, cytotoxicity tests, OECD129, Good Laboratory Practices, interlaboratory comparison
Background
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are some types of venom (e.g., from the puff adder or brown recluse spider). Treating cells with the cytotoxic compound can result in a variety of cell fates: The cells may undergo necrosis, stop actively growing and dividing or activate a genetic program of controlled cell death (apoptosis). Cytotoxicity assays are the tests used by researchers to screen for cytotoxicity in compound libraries. Researchers can either look for cytotoxic compounds, if they are interested in developing a therapeutic that targets rapidly dividing cells, or they can screen "hits" from initial high-throughput drug screens for unwanted cytotoxic effects before investing in their development as a pharmaceutical.
Cytotoxicity tests may be used as a substitute to in vivo tests that use animals. The concept of using in vitro cytotoxicity data to determine the starting doses for rodent acute oral toxicity tests was discussed and evaluated at the International Workshop on In Vitro Methods for Assessing Acute Systemic Toxicity convened in 2000.[1] The approach involves using an IC50 value from an in vitro basal cytotoxicity test with the Registry of Cytotoxicity (RC) regression to predict an LD50 value for use as a starting dose for the Acute Toxic Class (ATC) method or the Up-and-Down Procedure (UDP) test method.[2] Simulations showed that using in vitro cytotoxicity assays to estimate an LD50 to use as a starting dose in the UDP could potentially reduce animal use by 25 to 40 percent. Additionally, several tests have currently demonstrated the efficiency and effectiveness of alternative methods testing to reduce, refine, and/or replace the use of animals in testing.[1][2][3][4][5]
References
- ↑ 1.0 1.1 Interagency Coordinating Committee on the Validation of Alternative Methods (August 2001). "Report of the International Workshop on In Vitro Methods for Assessing Acute Systemic Toxicity" (PDF). National Institute of Environmental Health Sciences. https://ntp.niehs.nih.gov/iccvam/docs/acutetox_docs/finalrpt/finalall0801.pdf.
- ↑ 2.0 2.1 Spielmann, H.; Genschow, E.; Liebsch, M.; Halle, W. (1999). "Determination of the Starting Dose for Acute Oral Toxicity (LD50) Testing in the Up and Down Procedure (UDP) From Cytotoxicity Data". Alternatives to Laboratory Animals 27 (6): 957-66. PMID 25490464.
- ↑ Stokes, W.S.; Casati, S.; Strickland, J.; Paris, M. (2008). "Neutral red uptake cytotoxicity tests for estimating starting doses for acute oral toxicity tests". Current Protocols in Toxicology 36 (20.4): 20.4.1–20.4.20. doi:10.1002/0471140856.tx2004s36. PMID 20967741.
- ↑ EURL ECVAM (December 2014). "EURL ECVAM strategy to replace, reduce and refine the use of animals in the assessment of acute mammalian systemic toxicity". European Commission. pp. 46. https://eurl-ecvam.jrc.ec.europa.eu/eurl-ecvam-strategy-papers/strategy-acute-mammalian-systemic-toxicity.
- ↑ National Institute of Environmental Health Sciences. "Alternatives to Animal Testing". National Institutes of Health. https://www.niehs.nih.gov/health/topics/science/sya-iccvam/.
Notes
This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added. Some grammar were corrected when necessary.
