Table 1.
Examples of SCLC-CellMiner Capabilities
SCLC-CellMiner Explores and Validates | Method | Examples | Examples of Findings | |
---|---|---|---|---|
1 | cell line reproducibility and consistency | “Univariate Analyses: Plot Data:” expression of the same gene “across different datasets” (X and Y) | Figure 2 | cell lines are highly reproducible across datasets |
2 | omic data robustness and reproducibility | “Univariate Analyses: Plot Data:” expression, copy number variation, promoter methylation, mutations for the same gene “across datasets” (X and Y) | Figures 1B, 1C, and 2 | transcripts, promoter methylation, and gene copy number are highly reproducible across datasets |
3 | drug data robustness and reproducibility | “Univariate Analyses: Plot Data:” activity of the same drug “across datasets” (X and Y) | Figures 2E and 2F | warning: not all drugs are consistent across dataset |
4 | integrates all the SCLC cell line genomic datasets under SCLC-Global (NCI, GDSC, CCLE, CTRP, UTSW) | use the pull-down tabs for “Cell Line Sets” and choose “SCLC-Global” | Figures 4D, 6H, S2G, S2H, and S3C | the 119 SCLC cell lines can be classified in the four groups of NAPY; development of NAPY genomic signatures |
5 | integration with CellMinerCDB | open in parallel: https://discover.nci.nih.gov/cellminercdb | Figures 2, 4, and 5 | POU2F3 is selective for SCLC; YAP1 is expressed widely beyond SCLC; ASCL1 is co-expressed with NEUROD1 |
6 | select and compare subsets of cell lines based on tissue of origin or metadata: NAPY, TNBC, NSCLC | “Univariate Analyses:” select y axis: “Select Tissue/s of Origin” or “Select Tissues to Color” (NEUROD1, ASCL1, POU2F3, YAP1, NE) | Figures 2H, 5F, S3, and S6 | NEUROD1 and ASCL1 are also selectively expressed in CNS cancer cell lines |
7 | test phenotypic data (mda): NE, APM, EMT | “Univariate Analyses:” select “Data Type mda: NE, APM, EMT;” additional selection can be done for subset (see #6) | Figures 4H and 6 | NE cell lines have low antigen-presenting machinery (APM) score |
8 | tissue- or subset type-specific analyses (NAPY; NE) | “Select Tissue/s of Origin” or “Select Tissues to Color” | Figures 5, 6, and S4–S6 | YAP1 cell lines have lower replication and highest APM score |
9 | epigenetics: promoter methylation for any given gene | “Univariate Analyses: Plot Data:” expression of a given gene versus its methylation (X and Y “Data Type”) within a given “Cell Line Set” or across datasets (independent datasets can be tested for missing “Data Type” and confirmation) | Figure S1 | promoter methylation is a driver for gene expression (NAPY genes; SLFN11; MGMT; SMARCA1; CGAS) |
10 | gene amplification and deletions for any given gene | “Univariate Analyses: Plot Data:” expression of a given gene versus copy number (X and Y “Data Type”) within a given “Cell Line Set” or across datasets (independent datasets can be tested for validation and missing “Data Type”) | Figures 1, 3, and S1 | MYC genes and other oncogenes are often driven by copy number variation (CNV) |
11 | integrate and complement different datasets for common cell lines | “Univariate Analyses: Plot Data:” plot different parameters (“Data Type for” genomic or drug response) across “Cell Line Sets” (X and Y) to counter missing data in one dataset | Figures 1, 2, and 6 | drug response data in one dataset can be correlated with genomics of another dataset |
12 | genomic pathway discovery (coregulated genes and microRNAs) | “Univariate Analyses: Plot Data:” expression of a given gene (X or Y “Data Type”) within a given dataset or across datasets; also use the “Compare Patterns” tab | Figures 5, 6, S2, and S3 | ASCL1 and YAP1 are integrated in tight genomic networks connected with the NOTCH pathway |
13 | discover determinants of drug response and targeted drug delivery | “Univariate Analyses: Plot Data: Compare Patterns:” coregulated genes for a given gene (X or Y) within a given “dataset” (independent datasets can be tested for confirmation) | Figures 6 and S6 | resistance of YAP1 cell lines to chemotherapy and potential response to mTOR and immune checkpoint inhibitors; NAPY-specific antigen cell surface biomarkers |
14 | validate genomic determinant of drug response | “Univariate Analyses: Plot Data: Compare Patterns:” plot genomic parameter versus drug (X or Y “Data Type”) | Figure 6 | validation of SLFN11 for DNA damaging chemotherapy |
15 | examine drug correlations: COMPARE analyses | “Univariate Analyses: Plot Data: Data Type:” drug versus drug (X or Y); also select “Compare Patterns” to identify drug-drug correlations | Figure S1 | cell lines sensitive to etoposide are cross-sensitive to topotecan |
16 | multivariate models of drug response and genomic features | “Multivariate Analyses: Cell Line Set; Response Data Type; Predictor Data Type/s; Predictor Identifier:” enter drug and genomic parameters to be tested as identifier or use “LASSO” to discover additional non-redundant determinants of response | Figures 5B and 5D; Figure S3E | discover independent omic or drug parameters to build a molecular signature for drug response or gene expression |
17 | data download | “Univariate Analyses: View Data: Download” tabs or “Multivariate Analyses: Download” tab | Figure 6 | allow further in-depth analyses and data download in Excel |
18 | drug identifier conversion | not applicable | Figures 2E and 2F | allow drug identification across different sources |
Set off in quotation marks are the option tabs of SCLC-CellMiner (https://discover.nci.nih.gov/SclcCellMinerCDB/).