WEBVTT 1 00:00:01.320 --> 00:00:05.530 Welcome to the Integrated Chemical Environment, also known as ICE. 2 00:00:05.560 --> 00:00:08.170 This video will show you how to interpret 3 00:00:08.200 --> 00:00:14.420 results of a query run in the In Vitro to In Vivo Extrapolation or IVIVE tool. 4 00:00:14.450 --> 00:00:20.420 We will be viewing the results of an IVIVE query built in a previous video. 5 00:00:20.450 --> 00:00:22.660 If you have not yet viewed that video, 6 00:00:22.690 --> 00:00:26.260 you may want to do so before watching this one. 7 00:00:26.290 --> 00:00:31.700 Once the query is run, the window will switch to Results view. 8 00:00:31.730 --> 00:00:37.700 At the top of the Results view is a heading labeled "Download IVIVE files". 9 00:00:37.730 --> 00:00:41.260 Open the "Download IVIVE files" drop down 10 00:00:41.290 --> 00:00:44.980 to access a link to a downloadable output file. 11 00:00:45.010 --> 00:00:47.960 This is an Excel file that includes input 12 00:00:47.990 --> 00:00:53.020 parameters and calculated equivalent administered doses, or EADs. 13 00:00:53.050 --> 00:00:54.700 We'll discuss some other options 14 00:00:54.730 --> 00:00:59.760 for exporting your results as we're looking at the results displays. 15 00:00:59.800 --> 00:01:02.940 The IVIVE results view shows 16 00:01:02.970 --> 00:01:06.050 an interactive table and two interactive graphs. 17 00:01:06.080 --> 00:01:08.770 The "text" or "Excel" thumbnails above 18 00:01:08.800 --> 00:01:12.490 the table provide download options for the table data. 19 00:01:12.520 --> 00:01:15.290 The two graphs below the table display 20 00:01:15.320 --> 00:01:22.140 the EAD values and the in vtro bioactivity concentration used to calculate the EADs. 21 00:01:22.170 --> 00:01:27.180 The bioactivity concentration is expressed as either the half-maximal activity 22 00:01:27.210 --> 00:01:32.260 concentration, or AC50, or the activity concentration at cutoff, 23 00:01:32.290 --> 00:01:37.290 or ACC, depending on what was specified in the input. 24 00:01:37.320 --> 00:01:39.490 Above the table, we can see the number 25 00:01:39.520 --> 00:01:44.180 of rows in the table and the number of chemicals with returned results. 26 00:01:44.210 --> 00:01:49.180 Each row of the table represents a chemical-assay combination. 27 00:01:49.210 --> 00:01:51.210 Above the table and to the right, 28 00:01:51.240 --> 00:01:55.820 the dropdown labeled "Chemical Identifiers Not Returned By Query" 29 00:01:55.850 --> 00:02:01.160 provides a list of any identifiers in your query that have no relevant data in ICE 30 00:02:01.190 --> 00:02:03.480 for IVIVE. 31 00:02:04.080 --> 00:02:09.340 The first column of the table contains a concentration response curve button. 32 00:02:09.370 --> 00:02:15.220 Click on this button to send data from that row to the ICE Curve Surfer tool. 33 00:02:15.250 --> 00:02:20.890 This will display the activity curves for that chemical-assay combination. 34 00:02:20.920 --> 00:02:26.280 Refer to the Curve Surfer User Guide for details on this tool. 35 00:02:26.440 --> 00:02:32.280 The next three columns contain identifier information for each chemical. 36 00:02:32.680 --> 00:02:37.300 Clicking on the chemicals CASRN directs you to the page about that chemical 37 00:02:37.330 --> 00:02:42.420 in the NTP Chemical Effects in Biological Systems, or CEBS, database. 38 00:02:42.450 --> 00:02:45.220 This resource provides access to NTP 39 00:02:45.250 --> 00:02:48.500 studies that were conducted on the chemical. 40 00:02:48.530 --> 00:02:53.820 Clicking on the chemical's DtXSID directs you to the U.S. Environmental Protection 41 00:02:53.850 --> 00:02:58.180 Agency's CompTox Chemicals Dashboard entry for that chemical. 42 00:02:58.210 --> 00:03:00.180 This resource provides the chemical's 43 00:03:00.210 --> 00:03:05.610 structure and other physicochemical, and experimental properties. 44 00:03:05.640 --> 00:03:12.060 To filter results on a specific chemical, assay, mode of action, or mechanistic 45 00:03:12.090 --> 00:03:16.100 target, click the filter button below the column heading. 46 00:03:16.130 --> 00:03:21.880 This opens a dialog box where you can select items of interest. 47 00:03:25.040 --> 00:03:27.460 The "Number of rows" listed above the table 48 00:03:27.490 --> 00:03:30.740 will be updated to reflect the filtered results. 49 00:03:30.770 --> 00:03:35.580 The graphs below the table will also be updated based on the filtered results, 50 00:03:35.610 --> 00:03:39.820 and any filters you apply will be applied to data downloads. 51 00:03:39.850 --> 00:03:45.380 Clear filters by clicking the Clear Filter button above the table. 52 00:03:45.410 --> 00:03:47.300 Depending on the model parameters 53 00:03:47.330 --> 00:03:51.780 and the chemicals, warnings may be issued about the assay results. 54 00:03:51.810 --> 00:03:54.500 For example, a warning note appears when 55 00:03:54.530 --> 00:04:01.180 using the solve_gas_PBTK model to model a chemical whose physicochemical 56 00:04:01.210 --> 00:04:08.300 parameters suggest that it's nonvolatile. Warnings will appear in the "Flag" column. 57 00:04:08.330 --> 00:04:10.820 You can send your IVIVE parameters 58 00:04:10.850 --> 00:04:15.340 to other ICE tools to run additional queries by using the "Send filtered results 59 00:04:15.370 --> 00:04:19.220 to" dropdown list next to the download buttons. 60 00:04:19.250 --> 00:04:21.540 For details on the use and outputs 61 00:04:21.570 --> 00:04:26.180 of the other ICE tools, refer to their respective user guides. 62 00:04:26.210 --> 00:04:31.240 You can also copy chemical IDs to the clipboard. 63 00:04:31.520 --> 00:04:36.540 The graphs below the results table display two interactive plots. 64 00:04:36.570 --> 00:04:42.260 The upper graph shows a box-and-whisker plots of EAD results. 65 00:04:42.280 --> 00:04:44.860 The lower graph shows a violin plot 66 00:04:44.890 --> 00:04:51.020 of the in vitro bioactivity input data that the EAD prediction is based on. 67 00:04:51.040 --> 00:04:53.260 Any filters applied to the interactive 68 00:04:53.280 --> 00:04:57.180 results table will also be applied to the graphs. 69 00:04:57.210 --> 00:05:02.220 The plots are lined so that the EAD plot in the upper graph 70 00:05:02.250 --> 00:05:07.820 is directly above the bioactivity plot for the same chemical in the lower graph. 71 00:05:07.840 --> 00:05:13.220 The x axis of each plot is limited to displaying 20 chemicals. 72 00:05:13.250 --> 00:05:16.860 Use the "Select Page" dropdown and buttons 73 00:05:16.890 --> 00:05:22.620 above the EAD graph to select or browse pages. 74 00:05:22.650 --> 00:05:27.660 Tools above the plots allow you to select data visualization options and 75 00:05:27.690 --> 00:05:32.340 in vivo data overlays for the EAD results. 76 00:05:32.360 --> 00:05:34.660 If you use the one-compartment model 77 00:05:34.690 --> 00:05:40.500 for your query, the left-hand drop down list allows you to select the population 78 00:05:40.530 --> 00:05:47.900 distribution to apply to your EAD results: either the 50th or upper 95th percentile 79 00:05:47.920 --> 00:05:52.940 of the steady-state plasma concentration or Css. 80 00:05:52.970 --> 00:05:55.620 If you use the three-compartment or 81 00:05:55.650 --> 00:05:59.820 multi-compartment model, the only option is to view results based 82 00:05:59.850 --> 00:06:05.900 on the 50th percentile of maximum plasma concentration, or Cmax. 83 00:06:05.920 --> 00:06:08.380 Simulation of population variability 84 00:06:08.410 --> 00:06:14.420 of physiological parameter values is not currently available for these models. 85 00:06:14.450 --> 00:06:17.180 The right-hand drop down list allows you 86 00:06:17.210 --> 00:06:22.940 to select in vivo data to compare to your returned EAD values. 87 00:06:22.970 --> 00:06:25.700 Options provided by ICE include one 88 00:06:25.730 --> 00:06:34.480 estrogen modulation, one acute lethality, and two androgen modulation data set. 89 00:06:41.240 --> 00:06:44.180 If you uploaded your own in vivo data, 90 00:06:44.210 --> 00:06:47.660 you can select those to overlay on the graph as well. 91 00:06:47.690 --> 00:06:50.380 The labels for these data will be the ones 92 00:06:50.410 --> 00:06:55.540 you specified in the "Dataset" column of the upload file. 93 00:06:55.570 --> 00:06:57.997 Two check boxes to the right of the 94 00:06:58.197 --> 00:07:02.020 dropdown lists allow you to select other plot display options. 95 00:07:02.040 --> 00:07:06.900 The "Log Axis" box is checked by default. 96 00:07:06.920 --> 00:07:14.220 Unchecking it will change the y-axis on the EAD plot from log to conventional scale. 97 00:07:14.250 --> 00:07:17.700 Checking "Show Name" will change the x-axis 98 00:07:17.730 --> 00:07:23.840 label on both plots from the CASRNs to chemical names. 99 00:07:24.760 --> 00:07:27.780 Hover over either plot area to display 100 00:07:27.800 --> 00:07:31.421 a menu of tools in the top right corner to that can be used 101 00:07:31.621 --> 00:07:33.140 to adjust the graph display. 102 00:07:33.170 --> 00:07:35.580 The camera icon on the far left side 103 00:07:35.600 --> 00:07:42.500 of this menu will export the graph to a publication-quality image in a PNG file. 104 00:07:42.530 --> 00:07:44.340 Thank you for watching our video 105 00:07:44.360 --> 00:07:50.360 on interpreting results of a query run in the ICE IVIVE tool. For more detailed 106 00:07:50.390 --> 00:07:54.720 information on the IVIVE tool, go to "Help" and select "User Guides".