The DiseaseLinc tool performs disease enrichment analysis on lincRNAs using biomedical literature data. Kindly note that the resulting associations are only predictions and not the curated data.
Licence
The tool is free for non-commercial and academic use. Kindly contact us for commercial and non-academic use.
The tool uses the data from PubMed and MeSH. The list of lincRNAs and their parental protein-coding genes are obtained from Talyan et al. (2018) Nucleic Acids Research. Diseases are identified by MeSH terms from the C branch. Citations associated with diseases are identified using the MeSH annotations in PubMed and citations associated with lincRNAs are identified using gene2pubmed (obtained from NCBI FTP site) by using parental genes as a proxy.
Using the tool
Selection panel
The selection panel can be found on the left side of the webpage. This is used to sumbit the user input data for specfic analysis.
Analysis type
User can perform following four types of analysis:
LincRNA-set association
This associates a set of lincRNAs, considered altogether, to diseases. User can define the minimum number of lincRNAs considered for the association using the “Additional options (minimum number of lincRNAs)” settings. There is no limit to the number of lincRNAs the user can enter.
LincRNA to Diseases
This associates individual lincRNAs, considered independently, to diseases. There is no limit to the number of lincRNAs the user can enter. Each lincRNA will by independently associated with the diseases.
Dieases to LincRNA
This associates individual diseases, considered independently, to lincRNAs. There is no limit to the number of diseases the user can enter. Each disease will by independently associated with the lincRNAs.
LincRNA-set enrichment
This option performs disease enrichment analysis for a set of lincRNAs, considered altogether, based on the enrichment score (ES). The ES is calculated from the provided gene-level statistics (e.g. expression level or fold changes) using the Fast Gene Set Enrichment Analysis algorithm. Please enter, one per each line, ENTREZ gene IDs or ENSEMBL gene IDs for the lincRNAs (or the parental genes) and corresponding fold changes seperated by comma. The user can define the minimum number of lincRNAs considered for the enrichment using the “Additional options (minimum number of lincRNAs)” settings. There is no limit to the number of lincRNAs the user can enter.
Entering the data
User can enter the data in following two ways:
Paste a list of lincRNAs or diseases
Here user can paste the list of ENTREZ gene IDs or ENSEMBL gene IDs for the lincRNAs or MeSH Unique IDs for the diseases.
Or select lincRNAs or diseases from the list
Alternatively, user can select multiple lincRNAs or diseases by selecting their names from the drop down list. The user can start typing the name of desired lincRNA or disease to filter out the list.
Hint
For LincRNA-set association and LincRNA-set enrichment, at least two lincRNAs are required to perform the analysis
Click on example from the selection panel to load the predefined data
Additional options
Minimum number of disease-related citations for a lincRNA or lincRNA-related citations for a disease
Use this option to set minimum number of PubMed articles to be used for defining a reliable lincRNA-disease association.
For a LincRNA-set association, minimum number of lincRNAs significantly associated with a disease
Use this option to define minimum number of lincRNAs required to define the disease enrichment.
False Discovery Rate (FDR) cutoff
Use this option to change the stringency of results.
Click on Submit to perform the analysis!
Output panel
The output panel can be found on the right side of the selection panel. This consists of following four tabs:
Enrichment table
This shows the main analysis result in the form of a table. There will be a message above the table stating if all input terms are matched with the database. If not, missing terms will be displayed and excluded from the analysis.
The table may be divided in several pages, depending on the length, accessible from a navigation bar at the bottom of the table. By default, the table displays 10 rows per page. This can be configured using the Show NN entries option at the top left corner of the table. The table rows can be filtered for any term from any column using the Search option at the top right corner of the table.
By default, the table is sorted according to FDR values. The table can be freely sorted by clicking on the column header (Shift+Click for multi-column sorting).
Diseases, NCBI gene ID (parental gene), LincRNA, and citations are linked to MeSH, ENTREZ, ENSEMBL, and PubMed respectively. Click on them to open respective links in a new browser tab.
Output table definition
LincRNA-set association
- Disease: disease associated with specific lincRNAs (links to respective MeSH database entry)
- Gene Count: number of lincRNAs associated with specific disease
- NCBI gene ID (parental gene): ENTREZ gene IDs for the associated protein-coding parental genes of the lincRNAs (links to respective ENSEMBL entry)
- LincRNA: ENSEMBL IDs for the associated lincRNAs (links to respective ENSEMBL entry)
- Citations: number of citations used for computing lincRNA-disease association (links to respective PubMed entry)
- Fold change: (number of input lincRNAs significantly associated with the disease in the literature / number of input lincRNAs) / (total number of lincRNAs significantly associated with the disease in the literature / total number of lincRNAs)
- p-value: calculated by a Fisher’s exact test
- FDR: False Discovery Rate calculateed by Benjamini Hochberg method
LincRNA to Diseases
- Disease: disease associated with specific lincRNAs (links to related MeSH database entry)
- LincRNA: ENSEMBL IDs for the associated lincRNAs (links to respective ENSEMBL entry)
- NCBI gene ID (parental gene): ENTREZ gene IDs for the associated protein-coding parental genes of the lincRNAs (links to respective ENSEMBL entry)
- Citations: number of citations used for computing lincRNA-disease association (links to respective PubMed entry)
- p-value: calculated by a Fisher’s exact test
- FDR: False Discovery Rate calculateed by Benjamini Hochberg method
Diseases to LincRNA
- LincRNA: ENSEMBL IDs for the lincRNA associated with the disease (links to respective ENSEMBL entry)
- NCBI gene ID (parental gene): ENTREZ gene IDs for the protein-coding parental gene of the lincRNA associated with the disease (links to respective ENSEMBL entry)
- Disease: disease associated with specific lincRNA (links to related MeSH database entry)
- Citations: PubChem CID for the associated lincRNA (links to respective PubChem entry)
- p-value: calculated by a Fisher’s exact test
- FDR: False Discovery Rate calculateed by Benjamini Hochberg method
LincRNA-set enrichment
- All columns from the LincRNA-set association output
- ES: Enrichment Score reflecting the overrepresented at the top or bottom of a ranked list (same as Broad GSEA implementation)
- NES: Enrichment Score normalized to mean enrichment of random samples of the same size
- nMoreExtreme: a number of times a random gene set had a more extreme enrichment score value
- leadingEdge: lincRNAs that drive the enrichment
Enrichment plot
A plot, summarizing the output, will be generated in case of LincRNA-set association and LincRNA-set enrichment. This plot can be locally saved by clicking on the Download the plot as a PDF file button below the plot figure.
Download
The output table can be locally saved by clicking the Download button. This will generate a tab-seperated *.tsv file.
Documentation
This page can be accessed here.
Hint
For quick help, click on the small help icon to the right of Select analysis type option on the selection panel.
Responsible for the content
Dr. Piyush More
Email: piyusmor@uni-mainz.de
Telephone: +49-6131-39-23892
Institute of Organismic and Molecular Evolution (iOME),
Johannes Gutenberg-University Mainz,
Hanns-Dieter-Hüsch-Weg 15, 55128 Mainz
Germany
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