Validation of the Predictive Toxicogenomics Space with cell culture data

<b>Cell culture for <i>in vitro</i> cytotoxicity predictions</b>. To validate the predictive performance of the PTGS, a set of CMap instances for 38 compounds that were not included in the NCI-60 data set were assessed. MCF7 (ATCC® HTB22™), PC­3 (ATCC® CRL­1435™) and HL­60 (ATCC® CCL­240™) cell lines were obtained directly from American Type Culture Collection (LGC Promochem AB) and maintained at 37 °C with 5 % CO2 in a humidified incubator according to provider’s instructions. Cell number was titrated to ensure that cell proliferation remained in a linear-exponential phase throughout the experiment (1000-2000 cells per well were plated). Each experiment was performed from unique assay ready cells (same passage). Data quality and assay comparability were first verified by replicating the measurements for 36 instances for 16 different compounds already measured in NCI-60. Measurements were carried out at the Institute for Molecular Medicine Finland, FIMM. The authors want to thank Ida Lindenschmidt and the High Throughput Biomedicine unit at FIMM for technical support to cellular high-throughput screening assays.<br>Table 1. Raw data as % of cell viability after compound treatment. Molar concentrations from -8 to -4 on the log10 scale (5 doses) were employed. Columns: Compound, Cell Line, Cell.viability(%) (-8 to -4, log10.conc.).<br>Table 2. Calculated GI50 values for control treatments, 16 compounds which have corresponding cytotoxicity data in the NCI-60 DTP database. Columns: Chemical, CellLine, CMapDose (concentration at which CMap profile was measured), GI50.NCI60 (GI50 in the NCI60 DTP database), Batch.NCI60 (batch in the NCI60 database), Batch.FIMM (batch in FIMM dataset), GI50.FIMM (GI50 value in the FIMM dataset).<br>Table 3. Calculated GI50 values for test treatments, 38 compounds which have gene expression data in the Connectivity Map database (used to calculate PTGS cytotoxicity virtual GI50 scores). Columns: Chemical, CellLine, CMapDose (concentration at which CMap profile was measured), Batch.FIMM (batch in FIMM dataset), GI50.FIMM (GI50 value in the FIMM dataset).<br>