A Novel Method for Analyzing [Ca2+] Flux Kinetics in High-Throughput Screening
Driven by multiparameter fluorescence readouts and the analysis of kinetic responses from biological assay systems, the amount and complexity of high-throughput screening data are constantly increasing. As a consequence, the reduction of data to a simple number, reflecting a percentage activity/inhi...
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| Veröffentlicht in: | Journal of biomolecular screening 2006-08, Vol.11 (5), p.511-518 |
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| container_title | Journal of biomolecular screening |
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| creator | Gribbon, Philip Chambers, Chris Palo, Kaupo Kupper, Juergen Mueller, Juergen Sewing, Andreas |
| description | Driven by multiparameter fluorescence readouts and the analysis of kinetic responses from biological assay systems, the amount and complexity of high-throughput screening data are constantly increasing. As a consequence, the reduction of data to a simple number, reflecting a percentage activity/inhibition, is no longer an adequate approach because valuable additional information, for example, about compound- or process-induced artifacts, is lost. Time series data such as the transient calcium flux observed after activation of Gq-coupled G protein-coupled receptors (GPCRs), are especially challenging with respect to quantity of data; typically, responses are followed for several minutes. Based on measurements taken on the fluorometric imaging plate reader, the authors have introduced a mathematical model to describe the time traces of cellular calcium fluxes mediated by the activation of GPCRs. The model describes the time series using 13 parameters, reducing the amount of data by 90% while guiding the detection of compound-induced artifacts as well as the selection of compounds for further characterization. |
| doi_str_mv | 10.1177/1087057106287929 |
| format | Article |
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The model describes the time series using 13 parameters, reducing the amount of data by 90% while guiding the detection of compound-induced artifacts as well as the selection of compounds for further characterization.</description><subject>Animals</subject><subject>Biological assay</subject><subject>Calcium</subject><subject>Calcium - metabolism</subject><subject>Cells, Cultured</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>FLIPR</subject><subject>Fluorometry - methods</subject><subject>GPCR</subject><subject>HTS</subject><subject>Image Processing, Computer-Assisted - methods</subject><subject>Ion Transport - drug effects</subject><subject>Medical screening</subject><subject>Models, Theoretical</subject><subject>Pharmacokinetics</subject><subject>Receptors, G-Protein-Coupled - agonists</subject><subject>Receptors, G-Protein-Coupled - antagonists & inhibitors</subject><subject>Time Factors</subject><issn>2472-5552</issn><issn>1087-0571</issn><issn>2472-5560</issn><issn>1552-454X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9rFTEQx4MotrS9e5KcvMjWSXazyXp7POwPWuvBehIJ2ezsvpR9yTPZLbZ_fSP7UBBU5jBD-HyGIV9CXjE4ZUzKdwyUBCEZ1FzJhjfPyCGvJC-EqOH5r1nwA3KS0h0AMFmXuV6SA1bLGkpZHZKbFb0J9zjSjzhtQkf7EOnKm_Hh0fmBfl0b_vYbPRvnH_TKeZycTdR5euGGTXG7iWEeNrt5op9tRPTZOCYvejMmPNn3I_Ll7MPt-qK4_nR-uV5dF7Zq1FQwidAJ00MNVQNNZaAFUL2SKA0YAUy1XJUNs1y1hhmpWiGgbY1i1vCslkfkzbJ3F8P3GdOkty5ZHEfjMcxJ10oqVoL6L8gZaypWlxk8XcDBjKid78MUjc3V4dbZ4LF3-X3FqkaIJh-dBVgEG0NKEXu9i25r4oNmoH8GpP8MKCuv98fM7Ra738I-jgwUC5DMgPouzDFHkf618P3CY_7re4dRJ-vQW-xcRDvpLri_y0_xpKdC</recordid><startdate>200608</startdate><enddate>200608</enddate><creator>Gribbon, Philip</creator><creator>Chambers, Chris</creator><creator>Palo, Kaupo</creator><creator>Kupper, Juergen</creator><creator>Mueller, Juergen</creator><creator>Sewing, Andreas</creator><general>Elsevier Inc</general><general>Sage Publications</general><general>Sage Publications, Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>200608</creationdate><title>A Novel Method for Analyzing [Ca2+] Flux Kinetics in High-Throughput Screening</title><author>Gribbon, Philip ; Chambers, Chris ; Palo, Kaupo ; Kupper, Juergen ; Mueller, Juergen ; Sewing, Andreas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c498t-17e0d5af06049094a0b008f87e7a0a5018b28391c28ba1a78b550bba81ca2e0d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Biological assay</topic><topic>Calcium</topic><topic>Calcium - metabolism</topic><topic>Cells, Cultured</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>FLIPR</topic><topic>Fluorometry - methods</topic><topic>GPCR</topic><topic>HTS</topic><topic>Image Processing, Computer-Assisted - methods</topic><topic>Ion Transport - drug effects</topic><topic>Medical screening</topic><topic>Models, Theoretical</topic><topic>Pharmacokinetics</topic><topic>Receptors, G-Protein-Coupled - agonists</topic><topic>Receptors, G-Protein-Coupled - antagonists & inhibitors</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gribbon, Philip</creatorcontrib><creatorcontrib>Chambers, Chris</creatorcontrib><creatorcontrib>Palo, Kaupo</creatorcontrib><creatorcontrib>Kupper, Juergen</creatorcontrib><creatorcontrib>Mueller, Juergen</creatorcontrib><creatorcontrib>Sewing, Andreas</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biomolecular screening</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gribbon, Philip</au><au>Chambers, Chris</au><au>Palo, Kaupo</au><au>Kupper, Juergen</au><au>Mueller, Juergen</au><au>Sewing, Andreas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Method for Analyzing [Ca2+] Flux Kinetics in High-Throughput Screening</atitle><jtitle>Journal of biomolecular screening</jtitle><addtitle>J Biomol Screen</addtitle><date>2006-08</date><risdate>2006</risdate><volume>11</volume><issue>5</issue><spage>511</spage><epage>518</epage><pages>511-518</pages><issn>2472-5552</issn><issn>1087-0571</issn><eissn>2472-5560</eissn><eissn>1552-454X</eissn><abstract>Driven by multiparameter fluorescence readouts and the analysis of kinetic responses from biological assay systems, the amount and complexity of high-throughput screening data are constantly increasing. 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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Animals Biological assay Calcium Calcium - metabolism Cells, Cultured Drug Evaluation, Preclinical - methods FLIPR Fluorometry - methods GPCR HTS Image Processing, Computer-Assisted - methods Ion Transport - drug effects Medical screening Models, Theoretical Pharmacokinetics Receptors, G-Protein-Coupled - agonists Receptors, G-Protein-Coupled - antagonists & inhibitors Time Factors |
| title | A Novel Method for Analyzing [Ca2+] Flux Kinetics in High-Throughput Screening |
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