WEBVTT 00:00:00.000 --> 00:00:04.410 Welcome to the Integrated Chemical Environment, also known as ICE. 00:00:04.480 --> 00:00:09.330 This video will show you how to interpret results of a query run in the in vitro 00:00:09.400 --> 00:00:12.810 to in vivo extrapolation (or IVIVE) tool. 00:00:12.880 --> 00:00:18.090 We will be viewing the results of an IVIVE query built in a previous video. 00:00:18.160 --> 00:00:20.960 If you have not yet viewed that video, you may want to do so 00:00:21.026 --> 00:00:22.850 before watching this one. 00:00:22.920 --> 00:00:27.170 Once the query is run, the window will switch to Results view. 00:00:27.240 --> 00:00:32.650 At the top of the Results view is a heading labeled "Download IVIVE files". 00:00:32.720 --> 00:00:37.760 Open the "Download IVIVE files" dropdown to access a link to a 00:00:37.826 --> 00:00:39.490 downloadable output file. 00:00:39.560 --> 00:00:44.440 This is an Excel file that includes input parameters and calculated equivalent 00:00:44.506 --> 00:00:47.210 administered doses, or EADs. 00:00:47.280 --> 00:00:50.440 We'll discuss some other options for exporting the results while we're 00:00:50.506 --> 00:00:53.080 looking at the results displays. 00:00:53.280 --> 00:00:57.130 The IVIVE results view shows an interactive table 00:00:57.200 --> 00:00:59.690 and two interactive graphs. 00:00:59.760 --> 00:01:04.280 The "text" or "Excel" thumbnails above the table provide download 00:01:04.346 --> 00:01:06.010 options for the table data. 00:01:06.080 --> 00:01:12.320 Two graphs below the table display the EAD values and the in vitro bioactivity 00:01:12.386 --> 00:01:16.490 concentration used to calculate the EADs. 00:01:16.560 --> 00:01:21.760 The bioactivity concentration is expressed as either the half-maximal activity 00:01:21.826 --> 00:01:27.400 concentration, or AC50, or the activity concentration at cutoff, or 00:01:27.466 --> 00:01:31.960 ACC, depending on what was specified in the input. 00:01:32.680 --> 00:01:37.600 Above the table, we can see the number of rows in the table and the number 00:01:37.666 --> 00:01:40.530 of substances with returned results. 00:01:40.600 --> 00:01:45.570 Each row of the table represents a chemical–assay combination. 00:01:45.640 --> 00:01:49.010 Above the table and to the right, the dropdown labeled 00:01:49.080 --> 00:01:52.450 "Chemical Identifiers, Not Returned By Query", 00:01:52.520 --> 00:01:57.120 provides a list of any identifiers in your query that have no relevant data, (i.e., 00:01:57.186 --> 00:02:03.840 positive in vitro assay data or OPERA predictions) in ICE for IVIVE. 00:02:04.440 --> 00:02:09.570 The first column of the table contains a concentration–response curve button. 00:02:09.640 --> 00:02:14.840 Click on this button to send data from that row to the ICE Curve Surfer tool. 00:02:14.960 --> 00:02:19.890 This will display the activity curves for that chemical–assay combination. 00:02:19.960 --> 00:02:24.410 Refer to the Curve Surfer User Guide for details on this tool. 00:02:24.480 --> 00:02:29.680 The next three columns contain Identifier information for each chemical. 00:02:29.760 --> 00:02:33.880 Clicking on the chemical's CASRN, directs you to the page about 00:02:33.946 --> 00:02:40.800 that chemical in the NTP Chemical Effects in Biological Systems, or CEBS, database. 00:02:41.467 --> 00:02:44.840 This resource provides access to NTP studies that were 00:02:44.906 --> 00:02:46.610 conducted on the chemical. 00:02:46.680 --> 00:02:50.600 Clicking on the chemical's DTXSID, directs you 00:02:50.666 --> 00:02:55.480 to the US Environmental Protection Agency, CompTox Chemicals Dashboard entry 00:02:55.546 --> 00:02:56.970 for that chemical. 00:02:57.040 --> 00:03:01.200 This resource provides the chemical's structure and other 00:03:01.266 --> 00:03:03.930 physicochemical and experimental properties. 00:03:04.000 --> 00:03:08.290 To filter results on a specific chemical, assay, 00:03:08.360 --> 00:03:13.410 mode of action, or mechanistic target, click the filter button 00:03:13.480 --> 00:03:16.200 below each column heading. 00:03:16.640 --> 00:03:21.520 This opens a dialog box where you can select items of interest. 00:03:25.280 --> 00:03:29.160 The "Number of rows" listed above the table will be updated to reflect 00:03:29.226 --> 00:03:31.240 the filtered results. 00:03:32.000 --> 00:03:37.610 The graphs below the table will also be updated based on the filtered results, 00:03:37.680 --> 00:03:42.160 and any filters you apply will be applied to data downloads. 00:03:42.800 --> 00:03:47.210 Clear filters by clicking the "Clear Filter" button above the table. 00:03:47.280 --> 00:03:50.760 Depending on the model parameters and the chemicals, warnings may 00:03:50.826 --> 00:03:53.370 be issued about the assay results. 00:03:53.440 --> 00:03:59.690 For example, a warning note appears when using the solve_gas PBTK model 00:03:59.760 --> 00:04:02.960 to model a chemical whose physicochemical parameters suggest 00:04:03.026 --> 00:04:05.330 that it is nonvolatile. 00:04:05.400 --> 00:04:08.610 Warnings will appear in the "Flag" column. 00:04:08.680 --> 00:04:14.050 The graphs below the results table display two interactive plots. 00:04:14.120 --> 00:04:18.330 The upper graph shows a box plot of EAD results. 00:04:18.400 --> 00:04:24.450 The lower graph shows a violin plot of the in vitro bioactivity input data 00:04:24.520 --> 00:04:27.920 that the EAD prediction is based on. 00:04:28.240 --> 00:04:32.200 Any filters applied to the interactive results table will also 00:04:32.266 --> 00:04:34.690 be applied to the graphs. 00:04:34.760 --> 00:04:39.450 The plots are aligned so that the EAD plot in the upper graph 00:04:39.520 --> 00:04:45.570 is directly above the bioactivity plot for the same chemical in the lower graph. 00:04:45.640 --> 00:04:50.890 The x axis of each plot is limited to displaying 20 chemicals. 00:04:50.960 --> 00:04:55.610 Use the "Select Page" dropdown and buttons above the EAD graph 00:04:55.680 --> 00:04:57.890 to select or browse pages. 00:04:57.960 --> 00:05:03.520 Tools above the plots allow to to select data visualization options and in vivo 00:05:03.586 --> 00:05:06.960 data overlays for the EAD results. 00:05:07.560 --> 00:05:11.760 If you use the one-compartment model for your query, the left-hand dropdown 00:05:11.826 --> 00:05:18.490 list allows you to select the population distribution to apply to your EAD results: 00:05:18.560 --> 00:05:23.290 either the 50th or the upper 95th percentile of the 00:05:23.360 --> 00:05:27.840 steady-state plasma concentration, or Css. 00:05:28.560 --> 00:05:33.730 If you used any of the three-compartment or multi-compartment models, the only option 00:05:33.800 --> 00:05:37.960 is to view results based on the 50th percentile of maximum plasma 00:05:38.026 --> 00:05:41.050 concentration or Cmax. 00:05:41.120 --> 00:05:46.480 Simulation of population variability of physiological parameter values is not 00:05:46.546 --> 00:05:48.370 currently available for these models. 00:05:48.440 --> 00:05:53.360 The right-hand dropdown list allows you to select in vivo data to compare 00:05:53.426 --> 00:05:56.210 to your returned EAD values. 00:05:56.280 --> 00:06:04.090 Options provided by ICE include one estrogen modulation, one acute lethality, 00:06:04.160 --> 00:06:10.170 human exposure predictions, and two androgen modulation data sets. 00:06:10.240 --> 00:06:14.160 If you uploaded your own in vivo data, you can select those to overlay 00:06:14.226 --> 00:06:16.320 on the graph as well. 00:06:16.800 --> 00:06:20.690 The labels for these data will be the ones you specified in the "Dataset" 00:06:20.760 --> 00:06:22.570 column of the upload file. 00:06:22.640 --> 00:06:26.320 Two checkboxes to the right of the dropdown lists allow you 00:06:26.386 --> 00:06:29.450 to select other plot display options. 00:06:29.520 --> 00:06:33.170 The "Log Axis" box is checked by default. 00:06:33.240 --> 00:06:37.880 Unchecking it will change the y axis on the EAD plot from the log 00:06:37.946 --> 00:06:40.360 to conventional scale. 00:06:41.960 --> 00:06:47.170 Checking "Show Name" will change the x-axis labels on both plots 00:06:47.240 --> 00:06:50.570 from CASRNs to chemical names. 00:06:50.640 --> 00:06:56.050 Hover over either plot area to display a menu of tools in the top right corner 00:06:56.120 --> 00:06:59.410 that can be used to adjust the graph display. 00:06:59.480 --> 00:07:04.720 The camera icon on the far left side of this menu will export the graph as 00:07:04.786 --> 00:07:08.840 a publication-quality image PNG file. 00:07:10.520 --> 00:07:14.570 You can send your IVIVE parameters to other ICE tools 00:07:14.640 --> 00:07:19.080 to run additional queries by using the "Send filtered results to" dropdown 00:07:19.146 --> 00:07:22.440 list next to the download buttons. 00:07:22.640 --> 00:07:26.010 For details on the use and outputs of the other ICE tools, 00:07:26.080 --> 00:07:29.050 refer to their respective user guides. 00:07:29.120 --> 00:07:33.800 You can also copy chemical IDs to the clipboard. 00:07:34.000 --> 00:07:38.650 A new feature on all ICE tool webpages streamlines the citation of ICE. 00:07:38.720 --> 00:07:43.033 The "Cite ICE" button leads to an Acknowledgement webpage where you 00:07:43.433 --> 00:07:49.400 will find ICE citation formats, examples of citations, and references. 00:07:50.167 --> 00:07:53.720 Thank you for watching our video on interpreting results of a query 00:07:53.800 --> 00:07:55.560 run in the ICE IVIVE tool.