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Acknowledgements
The results published here are in large part based on data generated by the TCGA, CCLE and GTEx consortia. We sincerely thank the BioMart and cBioportal development teams for making source code publicly available and ICGC data portal development team for help with the implementation of the BioMart solution.
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Competing interests
This work was funded by Pfizer, Inc. and all authors were employees thereof at the time the work was performed. The authors declare no other competing financial interests.
Integrated supplementary information
Supplementary Figure 1 The OASIS web portal.
The menu bar, accessible from all web pages in OASIS, groups different functionalities into submenus such as "Analysis", "Plots" and "Database Search". The "About" section provides links to the user guide, a brief description of OASIS and other information. "Data Summary" contains two treemaps representing primary tumor and cancer cell line data in OASIS.
Supplementary Figure 2 Tumor vs. normal expression analyses of CDK4 using RNA-Seq data.
(A) Box plot showing over-expression of CDK4 in Glioblastomas but not in normal brain tissues by integrating RNA-Seq derived expression data from both TCGA and GTEx. The bottom, middle and top of each box represent the first, second and third quartiles respectively. The lower and upper plot whiskers represent the 1.5 IQR (inter-quartile range) of the first and third quartiles. (B) Volcano plot analysis identifying CDK4 as over-expressed in tumor vs. normal tissues in TCGA Lung squamous cell carcinoma. Up-regulated genes are shown in red while down-regulated genes are shown in blue. CDK4 was highlighted by the Gene Search function.
Supplementary Figure 3 OASIS-print visualization of alterations affecting CDK4, CDK6, CCND1 and RB1 in all CCLE cell lines.
Cell lines are sorted by CDK4 copy number in descending order.
Supplementary Figure 4 Gene report.
(A) The "Gene info" section provides a description of the gene as well as pathway associations. Gene-level frequencies of somatic mutation (green), copy number gain (red) and copy number loss (blue) are shown for primary tumors (B), cancer cell lines grouped by cancer types (C), and tumors and cell lines based on COSMIC (D). See Supplementary Table 3 for detailed descriptions of data fields in the Gene report.
Supplementary Figure 5 Query interface and Alteration report.
(A) Query interfaces for the Database Search and Plots share a common design. On the top left corner, the "View" drop-down menu allows users to choose a plot or database query analysis. "Select Datasets" lists all the datasets applicable for a particular analysis. Multiple datasets can be selected (dark orange) and analyzed in the same plot. "Restrict Search" provides filtering parameters applicable to the selected datasets. (B) Rows represent samples and columns represent key information about MET copy number changes at the sample level. For CNV alteration report, columns include cancer gene status, copy number value, CNV mutation type ("Amplification", "Neutral", "Deletion") and CNV segment type ("Focal" or "Broad"). See Supplementary Table 4 for detailed descriptions of data fields in Alteration reports.
Supplementary Figure 6 Plot layout.
(A) The top left menu provides the export function to print or save an image in PNG format; the "Mode" switch allows toggling between the zoom and select functions in the plot area; the "Search" function allows the user to find and highlight a specific sample or gene within the plot. (B) There are also links to data download, bookmark and programmatic access to the underlying data. (C) The plot resides in the main window with the legend box providing additional functionalities such as to show or hide data elements in the plot.
Supplementary Figure 7 Pan-cancer report.
Alteration types are represented by different color codes – mutations (green), copy number gains (red), copy number losses (blue) and expression outliers (orange). Rows can be sorted based on gene symbol ("Gene"), druggability score ("Dr"), cancer gene status ("Ts": Tumor Suppressor, "On": Oncogene) and alteration frequency values. Mouse over a heatmap cell to display the alteration frequency and click on the cell to fetch the Alteration report.
Supplementary Figure 8 Bar plot.
The y-axis represents the log2 copy number ratio (LRR) while the x-axis represents samples grouped by cancer type. The horizontal red line represent the cutoff values for amplification (LRR = 0.88) and the blue line represent the cutoff for deletion (LRR = -0.74). Bars are color coded to represent different CNV calls - amplification (dark red, LRR = 0.88), copy gain (light red, 0.88 > LRR = 0.32), neutral (gray, 0.32 > LRR > -0.42) copy loss (light blue, -0.42 ≥ LRR > -0.74) and deletion (dark blue, LRR ≤ -0.74).
Supplementary Figure 9 Scatter plot analysis of MET copy number changes vs. gene expression.
(A) User can choose multiple datasets by "ctrl+click", type in the gene symbol MET, and select the expression data type "RNA Seq (RSEM)" in the query interface. (B) The x-axis of the Scatter plot represents the log2 copy number ratio values while the y-axis represents the gene expression values (TPM). For each cancer, sample count and correlation coefficient value are shown in the legend. (C) Users can control what to display in the plot by selecting or de-selecting the cancer types in the legend. Shown in (D) is a Scatter plot of CNV and gene expression of MET in CCLE gastric tumor cell lines. Users can mouse over one cell line to open a pop-up window containing links to the Sample report and other analyses. Users can also click on "Mode: Zoom" to switch to "Mode: Select", which allows multi-selecting a list of samples with high expression and copy number gains. The "Selected samples" window would pop up to display sample names, alteration details and prevalence statistics for the selected samples.
Supplementary Figure 10 Box plot analysis of MET over-expression in tumors.
(A) The y-axis represents expression in TPM while the x-axis represents samples grouped by cancer type. Normal samples are shown in green and tumor samples are shown in red. Tumors with MET over-expression can be multi-selected to obtain additional information. (B) A Box plot combining MET expression from CCLE (red) and GTEx (green). (C) Zoomed-in view of MET expression in gastric cancer cell lines compared side-by-side with that of normal stomach tissues.
Supplementary Figure 11 OASIS-print of MET, KRAS and EGFR alteration patterns in CCLE cell lines.
The graphic view at the top represents genes as rows with each column representing an individual sample. The percentage of altered samples within the selected cohort is calculated for each gene and shown next to the gene name. Mutations are represented by green circles. Colors in the filled circles represent copy gain (red) and copy loss (blue), with the color gradient corresponding to different levels of copy gain/loss. Triangles represent gene expression up-regulation (red, point-up) and down-regulation (blue, point-down). Detailed information on the alteration values is available by selecting the sample cell in the visualization. In the tabular view below, each row represents a sample and each column represents a gene and alteration type. Users can sort and filter rows based on alteration values such as gene expression or mutant alleles. Sorting of the table view also controls the order of samples in the graphic view.
Supplementary Figure 12 Volcano plot.
MET and ERBB2 are among differentially expressed genes in TCGA Thyroid carcinoma (A) and Breast invasive carcinoma (B). The xaxis represents log2 expression fold-change (FC) in tumor vs. normal samples and the y-axis represents FDR (-log10). Up-regulated genes (FDR < 0.1 & log2-FC > 1.6) are shown in red while down-regulated genes are shown in blue (FDR < 0.1 & log2-FC < -1.6). The "Gene Search" function allows users to search and highlight MET and ERBB2 inside the plots. Genes can also be selected to retrieve links to Gene report or additional plot-based analyses of gene expression at individual sample level.
Supplementary Figure 13 ADC target analysis.
Expression analysis of ERBB2, a known ADC target, using Box plot (A), Box plot through integration of TCGA and GTEx data (B), Scatter plot (C) and OASIS-print (D).
Supplementary information
Integrated Supplementary Figures
Supplementary Figures 1–13 (PDF 14785 kb)
Supplementary Information
Supplementary Methods, Supplementary Note, Supplementary Table 1 and Supplementary Protocol (PDF 6739 kb)
Supplementary Table 2
Mapping between original and unified disease categories. (XLSX 16 kb)
Supplementary Table 3
Descriptions of data fields in the project, sample and gene reports. (XLSX 15 kb)
Supplementary Table 4
Descriptions of data fields in the project, sample and gene reports. (XLSX 14 kb)
Supplementary Table 5
Comparison of datasets and data types between OASIS and five cancer genomics web portals: cBioportal (http://cbioportal.org), UCSC (http://genome-cancer.ucsc.edu), ICGC (http://dcc.icgc.org/), IntOGen (HTTP://www.intogen.org), and MAGI (http://magi.brown.edu). (XLSX 11 kb)
Supplementary Table 6
Comparison of analytical functionalities between OASIS and existing cancer genomics web portals. (XLSX 12 kb)
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Fernandez-Banet, J., Esposito, A., Coffin, S. et al. OASIS: web-based platform for exploring cancer multi-omics data. Nat Methods 13, 9–10 (2016). https://doi.org/10.1038/nmeth.3692
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DOI: https://doi.org/10.1038/nmeth.3692
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