TAM 2.0 Tutorial

May 11, 2018

How to use and interpret the Analysis function?
How to use and interpret the Comparison function?
How to use the Query function?

Analysis Wizard

  1. Input your miRNA list through left panel.

    2. Note that this page accepts human miRNA genes (pre-miRNAs) as its input. If the mature miRNA names (e.g. hsa-miR-140-5p) are provided, it will be collapsed into the corresponding miRNA gene (hsa-mir-140). If the exact name of the duplicated miRNA gene is not specified (e.g. hsa-mir-24), it will be mapped to all of the duplicated miRNA genes (hsa-mir-24-1 and hsa-mir-24-2).

  2. Input your background miRNA (format same as step 1).
  3. Choose overrepresentation or underrepresentation.
  4. Limit the size of miRNA set (the number of miRNAs in each curated miRNA set) to be analyzed.
  5. Choose additional tag options.
    • Up and down: We also curated up-regulated (or disease-promoting) miRNAs and down-regulated (or disease-suppressing) miRNAs. By choosing this option, such up-/down-regulated miRNA (sub-) miRNA sets will be specifically analyzed.
    • Mask cancer-related terms: Because many experiments investigate cancer-related miRNAs, the cancer-related miRNA sets constitute a major part of our curated data. If you are not interested in cancer, select this option, and the cancer-related miRNA sets will be excluded from the analysis.
    • Mask non-standard terms: Some of our miRNA set terms cannot be mapped to the standard terminology databases (e.g. ICD-10-CM and Gene Ontology). It this option is chosen, these miRNA sets will be excluded from the analysis.
  6. Submit the request by clicking Run button.

Tabular Result of Analysis Function

Before the tabular result, a brief summary of the user’s input is provided (as indicated by the yellow arrows in the figure below).

In this tabular result page, users can:

  1. Click “Text file of the results” button to download the tab-delimited text file of the results.
  2. Click “Result Visualization” to generate plots illustrating the significant results. See the next section for details.
  3. View the detailed list of the associated terms. User can also move mouse over one miRNA set term to view and save the related miRNAs.
  4. Click the [details] link behind each term to see the detail information box about the miRNA-term association.

The Term Details table lists the cross-refence of the term to the standard terminology database including ICD-10-CM (ICD10CM), disease ontology (DO), NCBI MeSH term (MESH), NCBI OMIM (OMIM), human phenotype ontology (HPO) and gene ontology (GO). User can view the detail records in these databases by clicking the corresponding links.

While the Association Details table lists the PubMed ID (PMID) for each miRNA-set association. The miRNAs in input list are highlighted. User can view the detail PubMed reference records by clicking the corresponding links.

Graphical Result of Analysis Function

By clicking the “Result Visualization” in the tabular view of the analysis result, users are redirected to this page. User can generate plots illustrating the significant results, using the custom parameters:

  1. Choose the miRNA set category.
  2. Choose the method for evaluating the statistical significance (P-value/Bonferroni/FDR)
  3. Limit the range of top terms to be displayed.
  4. Generate the plots by clicking the Plot button.
  5. Download high quality PNG images of the plots by clicking the corresponding links.

In all, three types of plots are generated.

  1. Barplot

    2. The number after the miRNA set term is the count of input miRNAs which are presented in each miRNA set.

  2. Bubble plot

    3. This plot is similar to bar plot, whereas the size of bubble correlates with the count of input miRNAs which are presented in each miRNA set.

  3. Heatmap

    4. This heatmap depicts the holistic view of miRNA-miRNA set association. The color of each line in the heatmap correlated with the significance (P-value/Bonferroni/FDR, depends on the plot parameter selected above) of the association with each term.

Comparison Wizard

  1. Input your list of up-regulated miRNAs into the first box in the left panel.

    2. Note that this page accepts human miRNA genes (pre-miRNAs) as its input. If the mature miRNA names (e.g. hsa-miR-140-5p) are provided, it will be collapsed into the corresponding miRNA gene (hsa-mir-140). If the exact name of the duplicated miRNA gene is not specified (e.g. hsa-mir-24), it will be mapped to all of the duplicated miRNA genes (hsa-mir-24-1 and hsa-mir-24-2).

  2. Input your list of down-regulated miRNAs into the second box in the left panel (format same as step 1).
  3. Choose additional tag options.
    • Mask cancer-related terms: Because many experiments investigate cancer-related miRNAs, the cancer-related miRNA sets constitute a major part of our curated data. If you are not interested in cancer, select this option, and the cancer-related miRNA sets will be excluded from the analysis.
    • Mask non-standard terms: Some of our miRNA set terms cannot be mapped to the standard terminology databases (e.g. ICD-10-CM and Gene Ontology). It this option is chosen, these miRNA sets will be excluded from the analysis.
  4. Submit the request by clicking Run button.

Results of Comparison

User can generate plots illustrating the significant results, by simply 1) set the range of top terms to be displayed and 2) Generate the plots by clicking the Plot button.

In all, two types of plots are generated.

  1. Bar plot

    2. This bar plot illustrates the correlations (similarities) between user-provided de-regulated miRNAs and the de-regulated miRNAs in other disease conditions

  2. Bar plot

    3. This heatmap depicts the holistic view of miRNA de-regulation in the CUARATED DISEASE CONDITIONS. The palette correlates with the association score (de-regulation score, corrected for the specificity of miRNA de-regulation). The down-miRNAs are indicated by green boxes while the up-miRNAs are indicated by red boxes.

Query Wizard

  1. Users can browse the tree structure of the TAM 2.0 miRNA sets in the left panel. The miRNA set is organized in “miRNA set category -> miRNA set term -> member miRNAs” hierarchy. The tree structure can be expanded by clicking the “+” button, while be collapsed by clicking the “-” button. If the user clicks one “miRNA set term” or one “member miRNA”, the corresponding miRNA set will be shown in the right panel. Note that NO OPERATION IS NEEDED IF you actually intend to SEARCH the miRNA set BY KEYWORDS.
  2. Alternatively, users can SEARCH the miRNA sets by using the KEYWORDS. First, select the type of keyword (Term or miRNA) you are inputting.
  3. Then, input the keywords in the input box.
  4. Finally, click the Search button to perform the searching.
  5. Click the “How to Use” link to this tutorial if you want to view this help again.
  6. When the Query results are ready, user can select one or miRNAs to be saved by clicking the toggles before the miRNA names. User can also click Select All button to select all miRNAs in the Query results.
  7. User can save the selected miRNAs by clicking the Save button.

Filter, View and Save the Query Results

  1. As shown above, user can browse the tree structure of the TAM 2.0 miRNA sets in the left panel. If the user clicks one “miRNA set term” or one “member miRNA”, the corresponding miRNA set will be shown in the right panel.
  2. Alternatively, users can search the miRNA sets by using the keywords. In either way (browsing or searching), the keyword (if applicable) will be shown in the red shade on the top of the query result. Users can remove this keyword and undo the query by clicking the Clear button.
  3. User can limit the query results in one or more miRNA set categories, by clicking the toggles before the category name. Please WAIT until the filtration is done, as this process requires 5-20 seconds (depend on the performance of user’s computer).
  4. User can also filter the query results by input additional keywords in the input box.
  5. Click “Search in results” button to perform secondary searching within the previous query results, according to the additional keywords inputted.
  6. Click the “How to Use” link to this tutorial if you want to view this help again.
  7. When the Query results are ready, user can select one or miRNAs to be saved by clicking the toggles before the miRNA names. User can also click Select All button to select all miRNAs in the Query results.
  8. User can save the selected miRNAs by clicking the Save button.
  9. The miRNAs matches the keywords will be highlighted in red.
  10. User can view the detail information box about the miRNA-term association by clicking the [details] link behind each miRNA. This table lists the cross-refence of the term to the standard terminology database including ICD-10-CM (ICD10CM), disease ontology (DO), NCBI MeSH term (MESH), NCBI OMIM (OMIM), human phenotype ontology (HPO) and gene ontology (GO). User can view the detail records in these databases by clicking the corresponding links.

Download

  1. the hyperlink of source code of TAM_1.0.
  2. the hyperlink of source code of TAM_2.0.
  3. the hyperlink of all sets of miRNAs of TAM_2.0.

Help

    How to use?

    Query Results

    Welcome to TAM 2.0

    TAM 2.0 is the updated web server of our previously published miRNA set enrichment analysis tool, TAM (http://www.cuilab.cn/tam/) in 2010. Through manual curation of over 9,000 papers, a more than two-fold growth of reference miRNA sets has been achieved in comparison with previous TAM. We grouped miRNAs into six categories of miRNA sets: miRNA-family sets, miRNA cluster sets, miRNA-disease, miRNA-function sets, miRNA-TF sets and tissue specificity sets. Compared with the previous version of TAM, new functions for miRNA set query and result visualization are also enabled in the TAM 2.0. In all, TAM 2.0 provides a tool to mine the functional and disease implication behind miRNAs of interests.

    This website has been tested by using Chrome, Microsoft Edge and Firefox browsers. Microsoft IE may not work well.

    Here is a quick start tutorial:

    • For users who have a keyword of miRNA or set, and wish to browse the related miRNA sets, they would "Query" the miRNA sets in TAM 2.0 by using the keyword.
    • For users who have one list of interested miRNAs, and wish to investigate their functional or disease associations, TAM 2.0 can “Analyze” enrichment of these miRNAs in the curated miRNA sets, by using the statistical overrepresentation analysis.
    • For users who have paired lists of up-regulated and down-regulated miRNAs (perhaps obtained from transcriptome profiling), TAM 2.0 can “Compare” the submitted up-regulated and down-regulated miRNAs with our manually curated disease-promoting (or disease-activated) miRNAs and disease-suppressing (or disease-inhibited miRNAs). By doing so, correlation with the user-provided de-regulated miRNAs and those in other disease conditions will be calculated.
    • For more detailed tutorial, please click here.

    Step1: Enter miRNA list

    Step2: Enter background miRNA

    Step3: Choose

    Overrepresentation
    Underrepresentation

    Step4:Size of miRNA category.

    -

    Step5: Choose

    Up and down
    Mask cancer-related terms
    Mask non-standard terms

    Step6: Submit List

    (The analysis usually takes 30~60 seconds, please be patient while the analysis is running)

    Analysis Wizard

    Before you start: Please note, this page works for one list of interested miRNAs. If you simply wish to query the miRNA sets by a keyword (e.g. miRNA name), click here. If you have some up- and down-regulated miRNAs and are interested in the positive/negative correlations between your miRNAs with the de-regulated miRNA in other disease, you could also try the “comparison” tool.

    Step 1: Input your miRNA list through left panel.

    Note: This page accepts human miRNA genes (pre-miRNAs) as its input, so the hsa-mir- prefix is assumed and the duplicated miRNA genes (e.g. with -1 or -2 suffix) would be specified.

    An example:

    hsa-mir-140
    hsa-mir-18a
    hsa-mir-19a
    hsa-mir-22
    hsa-mir-24-1
    hsa-mir-324
    hsa-mir-339
    hsa-mir-361
    hsa-mir-423
    hsa-mir-574
    hsa-mir-604
    hsa-mir-93

    If the mature miRNA names (e.g. hsa-miR-140-5p) are provided, it will be collapsed into the corresponding miRNA gene (hsa-mir-140). If the exact name of the duplicated miRNA gene is not specified (e.g. hsa-mir-24), it will be mapped to all of the duplicated miRNA genes (hsa-mir-24-1 and hsa-mir-24-2).

    Step 2: Input your background miRNA (format same as step 1).

    Note: It is NOT a necessary choice. By default, TAM will use all miRNAs included in the curated miRNA sets as the background if the user KEEPS IT BLANK.

    Step 3: Choose overrepresentation or underrepresentation.

    By default, for miRNA set enrichment analysis, the overrepresentation is chosen.

    Step 4: Limit the size of miRNA set.

    This option limits the size of miRNA sets (the number of miRNAs in each curated miRNA set) to be analyzed.

    Step 5: Choose additional tag options.

    Up and down: We also curated up-regulated (or disease-promoting) miRNAs and down-regulated (or disease-suppressing) miRNAs. By choosing this option, such up-/down-regulated miRNA (sub-) miRNA sets will be specifically analyzed.

    Mask cancer-related terms: Because many experiments investigate cancer-related miRNAs, the cancer-related miRNA sets constitute a major part of our curated data. If you are not interested in cancer, select this option, and the cancer-related miRNA sets will be excluded from the analysis.

    Mask non-standard terms: Some of our miRNA set terms cannot be mapped to the standard terminology databases (e.g. ICD-10-CM and Gene Ontology). If this option is chosen, these miRNA sets will be excluded from the analysis.

    Step 6: Submit the request by clicking Run button.

    Source code of TAM_1.0: tam_1.0.zip.

    Source code of TAM_2.0: tam_2.0.rar. (standalone beta version, may not be up-to-date)

    All sets of miRNAs of TAM_2.0: mirna_sets.

    • News
      • May. 11, 2018: The help tutorial was enhanced. The known bugs were fixed.
      • May. 9, 2018 The information box showing PMIDs and term cross-reference was added. The known bugs were fixed and mis-assigned miRNAs were corrected.
      • Apr. 29, 2018 The heatmap visualization for Analysis and Comparison results became available. The secondary searching function in the Query page was enabled.
      • Apr. 10, 2018 The known bugs were fixed and mis-assigned miRNAs were corrected.
      • Dec. 4, 2017: The result visualization function was added.
      • Oct. 30, 2017: TAM 2.0 was made available.

    • Statistics
      • Currently, TAM 2.0 includes 1238 miRNA sets, where 1209 distinct miRNA genes are covered.

    • Contact

      • TAM 2.0 results from collaboration between groups from Hebei University of Technology and Peking University Health Science Center. We try to understand life science using computing.

      TAM 2.0 tool is free only for academic usage. For commercial useage, please contact the following PIs.

      Group PIs:

      Dr. Jianwei Li
      Institute of Computational Medicine, School of Computer Science & Engineering, Hebei University of Technology, Tianjin, China
      Email: lijianwei@hebut.edu.cn

      Dr. Yuan Zhou
      Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing, China
      Email: soontide6825@163.com

      Dr. Qinghua Cui (professor of bioinformatics, founder of previous version of TAM)
      Professor of bioinformatics, the founder of the first version of TAM
      Email: cuiqinghua@hsc.pku.edu.cn

    Step1: Enter up-regulated miRNA list

    Step2: Enter down-regulated miRNA list

    Step3: Choose the masking rules

    Mask cancer-related terms
    Mask non-standard terms

    Step4: Submit List

    Comparison Wizard

    Before you start: Please note, this page works for two list of miRNAs (one list of up-miRNAs and one list of down-miRNAs). If you simply wish to query the miRNA sets by a keyword (e.g. miRNA name), click here. If you have only one list of interested miRNAs to be analyzed, please use the “analysis” tool instead.

    Step 1: Input your list of up-regulated miRNAs into the first box in the left panel.

    Note: This page accepts human miRNA genes (pre-miRNAs) as its input, so the hsa-mir- prefix is assumed and the duplicated miRNA genes (e.g. with -1 or -2 suffix) would be specified.

    An example:

    hsa-mir-155
    hsa-mir-15a
    hsa-mir-205
    hsa-mir-30c-1

    If the mature miRNA names (e.g. hsa-miR-155-3p) are provided, it will be collapsed into the corresponding miRNA gene (hsa-mir-155). If the exact name of the duplicated miRNA gene is not specified (e.g. hsa-mir-30c), it will be mapped to all of the duplicated miRNA genes (hsa-mir-30c-1 and hsa-mir-30c-2).

    Step 2: Input your list of down-regulated miRNAs into the second box in the left panel.

    An example:

    hsa-mir-1-1
    hsa-mir-1266
    hsa-mir-150
    hsa-mir-23a
    hsa-mir-26a-2
    hsa-mir-427

    Step 3: Choose additional tag options.

    Mask cancer-related terms: Because many experiments investigate cancer-related miRNAs, the cancer-related miRNA sets constitute a major part of our curated data. If you are not interested in cancer, select this option, and the cancer-related miRNA sets will be excluded from the analysis.

    Mask non-standard terms: Some of our miRNA set terms cannot be mapped to the standard terminology databases (e.g. ICD-10-CM and Gene Ontology). It this option is chosen, these miRNA sets will be excluded from the analysis.

    Step 4: Submit the request by clicking Run button.


    Citation: Jianwei Li, Xiaofen Han, Yanping Wan, Shan Zhang, Yingshu Zhao, Rui Fan, Qinghua Cui, and Yuan Zhou. TAM 2.0: tool for microRNA set analysis. Nucleic Acids Research, Volume 46, Issue W1, 2 July 2018, Pages:W180–W185.
    Ming Lu, Bing Shi, Juan Wang, Qun Cao and Qinghua Cui. TAM: A method for enrichment and depletion analysis of a microRNA category in a list of microRNAs. BMC Bioinformatics 2010, 11:41