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 - User guide
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- MACE tools
- The MACE tools are divided into four parts.
 - Query flowchart
- Click each box to see the details.
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Query starts from A.Search chemical response/gene expression profile.
- ● For the chemical search, the result page shows B. Show structure & information and profile selection. On the other hand, for the gene search, the search result directs to C. Bar graph for profiles and two profile selection buttons.
- ● The query results are visualized in the order of bar graphs, a heatmap, and waterfall plots. The waterfall plots are the end of the query flow for mutation- or lineage-based profiles
- ● From the cell line-based profiles, the profile-based similarity search is available. The results of F. Search similar chemicals/genes direct to C. Bar graph for profiles (cell line-based).
- A. Search chemical response/gene expression profile
- A.1 Search chemical type
- Chemical response profile can be reached by various chemical search types.
There are several tabs and each of the tabs performs a particular search type. Click one of the tabs to perform the desired search type.
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- ● Chemical Name: Search chemical structures using chemical name.
It allows one to search part of the chemical name.
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- ● NSC ID: The NSC ID is a numeric identifier for chemicals in the Developmental Therapeutics Program (DTP) repository.
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- ● CAS Number Search: The CAS number is an identifier for chemical substances registered in Chemical Abstracts Service.
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- ● Structure Search: The structure search locates similar chemical structures based on 2D or 3D structure. Click Open Structure Editor to launch the chemical editor.
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- ● Structure editor: The structure editor allows you to draw or load a chemical structure. Clicking 2D-based search locates similarity/substructure/superstructure chemicals based on 2D fingerprints. Clicking 3D shape search compares the 3D conformers of the query structure against those in the pre-build 3D conformer database. The 2D structure database contains over 48,000 structures and the 3D conformer database consists of 2.1 million conformers.
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- A.2 Search gene type
- Gene expression profile can be searched by two options: gene symbol and Affymetrix ID. Click one of the tabs to perform the desired search type.
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- ● Gene Symbol: Search gene profiles using gene symbol.
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- ● Affymetrix ID: Search gene profiles using gene probe ID.
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- A.3 Find category-specific chemical response or gene expression
- Mutation- or lineage-specific chemicals or genes can be searched by using filters.
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- ● Find category-specific chemical response: Chemicals satisfying user specified conditions can be retrieved by using the following options. Refer the table below for information about the image.
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| Category selector | Users may select one of the mutation and the lineage categories. |
| Mutation/lineage selector | This selector will be changed based on the selection of a category. For each of the mutation and the lineage categories, 15 mutations and 9 lineages in NCI60 cell lines are listed, respectively. Select a particular mutation or lineage. |
| Quantity changes | Response differences can be specified, which indicate how much a quantity changes between cell lines with a specific category and all cell lines. |
| Ranges | Quantity changes can be combined with ranges. Higher than the specified fold change, lower than that, or either (higher or lower than that) can be searched. |
| Significance level | Three types of a significance level are provided. |
- ● Combined search options: Users can specify multiple conditions to search chemicals to exhibit high sensitivity to multiple mutation types.
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| Add condition | to add more conditions
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| Remove condition | to remove the specified condition
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| Toggle key | to combine specified conditions by ¡°And¡± or ¡°Or¡±.
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- ● Find category-specific gene expression:
Gene probes satisfying user specified conditions can be retrieved. The filtering options are the same with those of chemicals.
- B. Show structure & information
- B.1 Search by chemical identifier
- Select any tabs (Chemical Name/NSC ID/CAS Number), enter the given example identifier in the text box, and click the Search button.
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- B.2 Search by chemical structure
- Draw a structure by using the Structure Editor and select 2D-based Search or 3D shape Search.
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- ● 2D-based Search result: Chemicals with the similarity measure more than 0.5 will be returned.
Click the Substance column in each range for the structure information.
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- ● 3D-based Search result: At most 100 similar conformers are returned.
Click the Substance column in each range for the structure information.
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- B.3 Chemical structure information and profile selection
- Information about query chemical(s) is provided. Depending on the query, multiple chemicals can be returned. Further investigation of the chemicals is available by selecting one from three types of profiles.
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| Profile selector | Three types of profiles can be selected.
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| Chemical structure |
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| Chemical information | NSC ID, CAS number, molecular formula, molecular weight, and any chemical names
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- C. Bar graph for profiles
- C.1 Bar graph: mutation-based profiles
- In the image below, left shows the bar graphs for chemicals and right shows those for genes.
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| Bar graph | Multiple bar graphs for a chemical/a gene symbol may be shown if there are repeated experiments for the chemical/multiple gene probes matched.
▪ y-axis: fold change for chemicals and log2(fold change) for genes
▪ x-axis: 15 mutations
▪ red bar: significant level < 0.01
▪ hovering on each bar shows the corresponding value and its significant level together.
▪ clicking a bar graph will direct to the corresponding waterfall graphs.
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| Go to heatmap | A hierarchically clustered heatmap for all bar graphs in the page will be shown.
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- C.2 Bar graph: lineage-based profiles
- In the image below, left shows the bar graphs for chemicals and right shows those for genes.
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| Bar graph | Multiple bar graphs for a chemical/a gene symbol may be shown if there are repeated experiments for the chemical/multiple gene probes matched.
▪ y-axis: fold change for chemicals and log2(fold change) for genes
▪ x-axis: 9 lineages
▪ red bar: significant level < 0.01
▪ hovering on each bar shows the corresponding value and its significant level together.
▪ clicking a bar graph will direct to the corresponding waterfall graphs.
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| Go to heatmap | A hierarchically clustered heatmap for all bar graphs in the page will be shown.
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- C.3 Bar graph: cell line-based profiles
- ● Cell line-based profiles for chemicals
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| Bar graph | Multiple bar graphs for a chemical may be shown if there are repeated experiments for the chemical.
▪ y-axis: z-score based on -logGI50
▪ x-axis: NCI60 cell lines grouped by lineages
▪ hovering on each bar shows the corresponding value.
▪ hovering on each cell line name shows the corresponding lineage.
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| Go to heatmap | A hierarchically clustered heatmap for all bar graphs in the page will be shown.
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- ● Cell line-based profiles for genes
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| Profile selector | For genes, search gene expression profile directs to this page with cell line-based profiles. Mutation- or lineage-based profiles can be selected. |
| Bar graph | Multiple bar graphs for a gene may be shown if there are multiple gene probes matched.
▪ y-axis: log2(gene expression)
▪ x-axis: NCI60 cell lines grouped by lineages
▪ hovering on each bar shows the corresponding value.
▪ hovering on each cell line name shows the corresponding lineage.
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| Go to heatmap | A hierarchically clustered heatmap for all bar graphs in the page will be shown.
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- D. Heatmap for profiles
- D.1 Heatmap: mutation- and lineage-based profiles
- In the image below, left shows the bar graphs for chemicals and right shows those for genes. The first row displays mutation-based profiles and the second one displays lineage-based profiles.
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| Heatmap | All profiles displayed in the format of bar graphs are biclustered.
▪ color bar: it ranges various depending on the clustered bar graphs.
▪ y-axis: chemicals or genes
▪ x-axis: 15 mutations or 9 lineages
▪ hovering on each lattice shows the corresponding value and its significant level together.
▪ clicking any row on the heatmap will direct to the corresponding waterfall graphs.
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- D.2 Heatmap: cell line-based profiles
- In the image below, the first row displays a heatmap for chemicals and the second one displays a heatmap for genes.
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| Heatmap | All profiles displayed in the format of bar graphs are biclustered.
▪ color bar: it ranges various depending on the clustered bar graphs.
▪ y-axis: chemicals or genes
▪ x-axis: NCI60 cell lines
▪ hovering on each lattice shows the corresponding value.
▪ hovering on each cell line name shows the corresponding lineage.
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| Similarity selector | First select one chemical or gene on the heatmap, then click one of the Search buttons. For the selected chemical or gene, chemicals/genes with similar profile will be retrieved.
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- E. Waterfall plot for profiles
- For mutation- and lineage-based profiles, waterfall plots are available.
- E.1 Waterfall plot: mutation-based profiles
- In the image below, the first row displays a part of 15 waterfall plots for chemicals and the second one displays that for genes.
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| Waterfall plot | Totally 15 waterfall plots for 15 mutations are displayed.
▪ title for chemicals: lineage name, fold change for chemicals and enrichment score with the significant levels for the lineage
▪ title for genes: lineage name, log2(fold change) for genes and enrichment score with the significant levels for the lineage
▪ y-axis: z-score for chemicals and log2(gene expression) for genes
▪ x-axis: NCI60 cell lines sorted by the value of y-axis
▪ red dot: cell lines with the corresponding lineage
▪ hovering on each dot shows the name of the corresponding cell line.
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- E.2 Waterfall plot: lineage-based profiles
- In the image below, the first row displays a part of 9 waterfall plots for chemicals and the second one displays that for genes.
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| Waterfall plot | Totally 9 waterfall plots for 9 mutations are displayed.
▪ title for chemicals: mutation name, fold change for chemicals and enrichment score with the significant levels for the mutation
▪ title for genes: mutation name, log2(fold change) for genes and enrichment score with the significant levels for the mutation
▪ x-axis: NCI60 cell lines sorted by the value of y-axis
▪ red dot: cell lines with the corresponding mutation
▪ hovering on each dot shows the name of the corresponding cell line.
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- F. Search similar chemicals/genes
- The profile-based similarity search starts from D2. Heatmap: cell line-based profiles. The following step explains an example of the profile-based similarity search between chemicals. The search between genes or between a chemical and a gene also also has similar steps.
- Step 1> Select one row on the heatmap and click the Search button for Chemicals with similar profile, for example.
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- The profile-based similarity measure is Pearson Correlation Coefficient (PCC) between two cell line-based profiles of chemicals. The chemicals with the absolute PCC value more than 0.6 will be displayed. If the Search button for Genes with similar profile is clicked, the genes with similar profile will be retrieved.
- Step 2> The search results are represented as bar graphs of the cell line-based profiles. For each retrieved chemical, the PCC value is added next to the chemical name. Click the Show heatmap button.
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- Step 3> For the retrieved chemicals, a heatmap is generated. Click one on the heatmap for the details.
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- Step 4> For the selected chemical, its structure and primary information are displayed.
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- Cell line information
- This search provides cell line information of NCI60.
Searches can be done by search cell line or search mutation/lineage
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- ● Type a name of a specific cell line.
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- ● The result shows the lineage and the mutation information of the query cell line.
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- ● Type a specific mutation or lineage.
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- ● Depending on the query (mutation/lineage), the result shows all related cell line information.
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- Last update: November 2014
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