User guide

 

In case of any problems or questions regarding the PD map content or associated tools please, contact Marek Ostaszewski or Stephan Gebel, or use “Send feedback” functionality available within the map browser.

Download the new User Guide as pdf

How to start

Introduction

The Parkinson’s disease (PD) map (http://pdmap.uni.lu)

  • displays disease-related molecular and biochemical pathways within a neuronal cell system, focused on a dopaminergic neuron, adjacent cells (i.e., astrocytes, microglia) and cellular structures (i.e., blood-brain-barrier, synaptic terminals).
  • integrates more than 1300 manually curated publications and over 250 entries from public databases such as Reactome or KEGG (as of Sept, 2017).
  • has an intuitive “Google Maps” display enabling easy navigation.
  • is composed of
    • species (here: elements, entities) such as genes, proteins, molecules, complexes, annotated with relevant database entries.
    • reactions (or interactions) describing relations between species, annotated with relevant literature and/or database entries.
  • “LEGEND” button (right upper side, blue panel) provides details on the format of elements and interactions.

Pathways and Compartments view

 “Pathways and compartments” is the default view providing an overview on the content.

 

Fig. 1: Pathways (grey) and compartments (coloured) view of the PD map
  • provides hierarchical information on the cellular structures, processes and complexes.
  • clicking in a compartment provides additional information in the left side panel.
  • zooming out / in provides higher level compartment view or more detailed view on molecular species and interaction, respectively (see also chapter 2).

Biological overview

To get a view of the biological systems that are modelled in the PD map click on the button “SHOW OVERVIEW” (Fig.2; red rectangle)

Fig. 2: Biological overview of the PD map
  • Each figure contains three standard buttons in the left upper corner (“home”, “back”, ”to map”) to navigate through the pictures or to go to the respective area in the PD map.
  • Clicking on the marked areas leads you to more detailed pictures of the surrounded area or, if no further downstream picture is available, it links to the respective areas in the PD map.

Important for tablet and smart phone use:

Do not tip to the links in the case you have enlarged the biological view. The links to the PD map only work proper when the biological view has its original size.

Submaps

  • To maintain overall structure of the PD map, some parts of the main network where displayed in separate, more detailed submaps.
  • The submaps are fully operational; i.e., search functions and data display works simultaneously on the whole PD map and on the submaps.
  • Enter submaps by clicking the "SUBMAPS" tab . Click on magnifier to enter the receptive submap.
  • Alternatively, you may click on dedicated elements in the map and open it from the left side information panel.

How to browse and search

Browse

  • An intuitive “Google Maps" display enables easy navigation through the PD map.
  • Clicking any element in the PD map (e.g., proteins, molecules or phenotypes) provides detailed annotations and links to external databases, which are displayed in the left panel (Fig. 3)presumably SERCH GENERIC is active. Otherwise, the information is visible on the bottom of the left panel (see Fig. 11: CREPPB protein).

Fig. 3: Screenshot showing annotations of the protein: MARK2 (microtubule affinity-regulating kinase 2)

  • By clicking on the bubble pinned to the element (Fig. 4A red arrow) additional information is displayed in a pop up box.
  • For genes, miRNAs and proteins a special pop up box enables the search for interacting drugs, chemicals and miRNAs. First click on the element, then on the coloured number above and then the related checkbox (“Show all”) (Fig. 4).
  • For more information on the different tools on drugs, chemicals and miRNAs interaction see related chapters 2.3, 2.4, and 2.5.

Fig. 4: Additional information and functions in relation to MARK2 displayed as pop up.

  • Clicking on a connection line between elements (Fig. 5) provides detailed information on the underlying reaction (coloured in blue), displayed in the left panel. This includes information on reactants and links to the underlying sources (i.e., PubMed, Reactome or KEGG).

Fig. 5: Screenshot showing annotations of reaction re4026: MUL1 mediates ubiquitination of MFN2. Activated reaction is coloured in blue.

Search: GENERIC

  • The "GENERIC SEARCH" function is located in the upper part of the left panel
  • All elements (e.g., genes, proteins, small molecules, complexes) are searchable
  • Search function also works with synonyms
  • Search for multiple elements: separate names by semicolon (see Fig.6)
  • Clicking on “PERFECT MATCH” reduces the search to those elements that exactly correspond to the input
  • The location of the searched species is displayed on the PD map by coloured circles.
  • Results from searches for multiple elements are displayed with different colours.
  • The left panel provides annotations on the elements and the reaction types including links to external databases.
  • Search for reactions: type in:reaction: reXXXX (XXXX = reaction number)
  • Search for publications and related interaction: type pubmed:XXXXXXX (where XXXXXXX = PubMed ID).
  • Search for publications also works with the specific publication list. Under “INFO” you findthe link to the list of the current publications curated into the PD map. This list is fully searchable and contains links back to the PD map.
  • Clicking on “CLEAR” (right upper corner) will remove all search results from the PD map

Fig. 6: Search for Mitofusin2 (MFN2) and Mulan1 (MUL1): All locations of MFN2 (red circle) and MUL1 (blue circle) are displayed in the PD map. Left panel shows annotations.

Search: How to use drug interface

  • The “DRUG” interface allows to search for potential drug targets within the PD map.
  • Activate the “DRUG” tab under “SEARCH”.
  • Type drug names (synonyms or brand names also work) in the search field.
  • Separate multiple search by semicolon
  • Potential targets are fetched from the drug databases DrugBank and ChEMBL, displayed and marked in the PD map by numbers within a coloured rectangle.
  • Additional information concerning the drugs and the potential targets, including links to drug databases and PubMed is provided in the left panel.

Fig. 7: Search for the drug “Mirapex”. (A) Information panel displays information on Pramipexole as Mirapex is a brand name for the drug Pramipexole. Drug targets are displayed in the map. (B) Pramipexole targets dopamine receptors (DRD2 and DRD1). (C) The bubble pinned to the target (e.g., DRD1) provides information on drug interaction and offers additional functionalities to search for other drugs, chemical or miRNA that interacts with the DRD1 protein (see also Fig. 4B, Fig. 8, Fig. 9).

Please note:

  • If within a multiple search several drugs hit the same element, the bubbles will overlap and only the one from the second search is visible on that element (see Fig. 8)
  • The same happens when search queries from different tools targeting the same element in the PD map. Only the bubble from the first search is visible on the element that is targeted by the two or more search queries.
  • All results are always displayed in the left panel.
  • All results are displayed simultaneously in a pop up information field when clicking on the bubble pinned to the target (see Fig. 4; Fig. 7C, Fig. 8 and Fig 11).
  • At the end of the list, the left panel shows also targets that are not in the PD map (see Fig.9).

Search: How to use chemical interaction interface

  • The “CHEMICAL” interface allows to search for potential interactions of chemicals with the PD map elements based on the Comparative Toxicogenomics Database.
  • Only interactions that are annotated to the disease term Parkinson’s disease (MeSH ID: D010300) in the CTD database are considered.
  • Activate “CHEMICAL” tab under “SEARCH”.
  • Type in the full name of a chemical according to the ctdbase/chem database; abbreviations or synonyms do not work (e.g., MTPT does not work but 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine).
  • If the chemical name includes comma(s), place a semicolon behind the name to avoid a segmentation of the name during processing.
  • Always separate multiple search by semicolon.
  • Potential targets are fetched from the Comparative Toxicogenomics Database, displayed and marked in the PD map by a number within a coloured circle.
  • Additional information concerning the chemical and the potential targets, including links to CTD databases and PubMed are provided in the left panel.

Fig. 8: Search for the interaction targets of “rotenone” and “hydrazine”. Information panel displays information on “hydrazine”. Interacting species are labelled in the map (green bubbles for hydrazine; blue bubbles for rotenone). Clicking on framed number above the target (e.g., green framed “3”) provides information on the target (i.e., HSPA9) and chemical interactions and offers additional functionalities to search for other drugs, chemical or miRNA that interacts with the target (see also Fig. 4; Fig. 7C, and Fig 11). Please note: If within a multiple search several drugs hit the same element, the bubbles will overlap and only the one from the second search is visible on that element.

Search: How to use miRNA interface

  • The “MiRNA" interface allows to search for potential targets of miRNA within the PD map elements based on the miRNA database: miRTarBase.
  • Only target interactions that have strong evidence according to miRTarBase criteria (i.e., reporter assays, western blot or qPCR analysis) are considered.
  • Activate “MiRNA” tab under “SEARCH”.
  • Type in the miRNA ID, use only mature sequence IDs e.g., hsa-miR-125a-3p (see:www.mirbase.org).
  • Separate multiple search by semicolon.
  • Matching targets from the miRTarBase are displayed in the PD map by pinned bubbles (here: coloured triangles).
  • Additional information concerning the miRNAs and the potential targets, including links to miRTarBase and PubMed is provided in the left panel.

Fig. 9: Search for targets of hsa-miR-125a-3p. Left panel displays information on hsa-miR-125a-3p and its targets. Targets are marked by pinned bubbles (green triangles) in the PD map. Clicking on the pinned bubble provides information on miRNA interactions and offers additional functionalities to search for other miRNA, drugs, chemical that interacts with the target. Left panel shows also targets that are not in the PD map (here: GPC4).

How to display implemented data sets

  • The visualization of specific data sets on differential gene regulation is accessible via the “OVERLAYS” tab (left panel). Different data sets are indicated under “GENERAL OVERLAYS”
  •  Ageing brain: Differentially expressed genes in healthy aging brain. Enrico Glaab (LCSB) contributed this data derived from Allen Brain Atlas database. red: stronger expression in aged brain; blue: lower expression in aged brain. See: Glaab and Schneider, 2015.
  • PD substantia nigra: Differential gene expression (FDR <= 0.05) from the analysis of eight transcriptome data sets, comparing human post mortem brain samples from PD vs. healthy controls. red: stronger expression in PD; blue: lower expression in PD. See: Fujita et al., 2013.
  • PD UK GO Project genes: Genes annotated by the Parkinson's disease GO Annotation Project. dark green: high priority gene list, light green: Parkinson’s-relevant protein. See: Foulger e al., 2016.
  • The expression data could be downloaded under “Data” (note: the value column in the downloaded list shows normalized expression values)
  • Click boxes to display the respective data set on the PD map.
  • Pathways and compartment view provides an overview on cellular processes affected by the visualized data (Fig. 10A)
  • Detailed differential expression (red rectangle: up regulated, blue rectangle: down regulated) is best visible using the colourless overlay “Empty” (Fig. 10B)

Fig. 10: Overlay of the PD substantia nigra data set to the PD map. (A) Pathways and compartment view. (B) Empty view

  • Displaying multiple data set is possible by ticking several checkboxes in the “View” column. Results from different data sets are simultaneously displayed by subdivided coloured rectangles (Fig. 11)
  • Additional information is provided when clicking on the species (Fig. 11)

Fig. 11: Overlay of PD substantia nigra data set and ageing brain data set to the PD map. Clicking on CREBBP provided detailed information in a pop up box and on the bottom of the information panel. In addition, information on Interacting drugs, chemical or microRNA can be displayed (see Chapters: 4, 5, and 6)

How to display custom data sets on the PD map

  • A personal account is needed to upload data.
  • The account is for free.
  • Click on the “INFO” tab. Click on “Request an account” under USER DATA.
  • User name and password will be provided by e-mail.
  • The account enables the upload of 100 separate data sets.
  • After login, user personal data are displayed in the INFO tab.
  • To upload own data sets, click on the “OVERLAYS” tab. This opens the menu for data set upload and management (“USER-PROVIDED OVERLAYS”)
  • Under “Add overlays” you find two possibilities to upload data sets and highlight elements on the PD map (see Fig. 12)
    • Upload and highlight a list of elements
    • Upload a list of element names and related expression values (as txt.file)

Fig. 12: Screenshot: “Add overlays” form.

Upload and highlight a list of elements

  • Click on “Add overlays” and fill in the form.
    • Name (default)
    • Description (free text)
    • Provide list of elements (one per line)
  • This list must contain the name of elements as it appears in the PD map (e.g., HGNC name for proteins and genes; CHEBI name for simple molecules)
  • The list may contain names for different element types at the same time (see Fig. 13A)
  • Click UPLOAD starts the process
  • The new file will appear in USER-PROVIDED OVERLAYS.
  • A short report will be send by mail (“MapViewer notification”).
  • Data are visualized by green colour on the PD map after clicking the view box (Fig. 13B).

Fig. 13: Upload (A) a list of elements to the PD map and visualisation (B)

Upload of a data file: Data preparation

  • Data file needs to be uploaded as a txt. file that consists of two columns
    • first column (headline = name) contains HGNC gene symbols
    • second column (headline = value) contains values between -1 and 1
  • As both proteins and genes are defined in the PD map by the uniform HGNC identifier and HGNC gene symbol, data derived from protein or gene expression will be displayed on gene and protein species in the PD map.
  • To upload data from other species than human, the species-specific identifiers need to be translated to HGNC identifiers.
  • The differential expression values (fold changes) needs to be normalized into a range between -1 to 1 (see Fig. 14).

Fig. 14: Differential gene expression data (excel file) were edited and transformed into a txt. file before upload.Normalization applied here: fold change (f.c.) >5 is set 1; f.c. <-5 set -1; f.c. between -1.5 and 1.5 is set 0; f.c.between -5 and -1.5 as well as 1.5 and 5 are normalized by dividing the value by 5.

Upload of a data file: Data upload

  • Click on the “OVERLAYS” tab. This opens the menu for data set upload and management (“USER-PROVIDED OVERLAYS”)
  • Click on “Add overlays”
    • Fill in form
    • Name (default)
    • Description (free text)
    • Click on “Browse” an select the file to be uploaded
    • Click “UPLOAD” to start the process
  • The new file will appear in USER-PROVIDED OVERLAYS.
  • A short report will be send by mail (“MapViewer notification”).
  • Data could be visualized on the PD map by clicking on view. Color code: Blue for down regulation and Red for up regulation
  • Elements are automatically coloured by the following colour codes in accordance to their dedicated values

Please note:

  • Combining display of multiple data sets from “GENERAL OVERLAYS” and “USER-PROVIDED OVERLAYS” is possible by clicking different data sets under “View”. Results are displayed by subdivided coloured rectangles (see Fig. 11)
  • In general, all PD map elements can be individually coloured on the PD map. If you like to colour elements individually contact us directly
  • To upload data from other species (e.g., mouse), gene and protein names has to be translated to human HGNC identifier.
  • All uploaded data are accessible by the system administrators due to technical reasons but they are not visible by any other user.

How to provide comments and feedback

  • Right click with the mouse in the PD map at the position where the comment is related to (note: this feature does not work on tablets and smart phones).
  • Click on: “Add comment”, fill in the form (use the dropdown list for “Type”) and press send button (Fig. 15).
  • The curation team will be notified on new comments and respond to them immediately.
  • The comment (without personal information) will be visible on the PD map if “Pinned” is checked (set by default)

Fig. 15: Screenshot shows the comment field

  • To see all pinned comments, click on the button “COMMENTS” (red circle, left upper corner, Fig. 16).
  • Clicking on the comment icon “ ” in the PD map displays the content (see Fig. 16)

Fig. 16: Screenshot after activating the “COMMENTS” button (red circle), displaying position of all pinned comments. Details of the specific comment on re4026 is visible after clicking on the related icon.

How to extract information from the PD map

Export function

  • Go to INFO tap and click on “EXPORT”button (red arrow).

Fig. 17: Export function

  • Use the tab “ELEMENT EXPORT” to select specific elements for download.
  • Use the tab “NETWORK EXPORT” to select specific networks for download (only SIF files).
  • Use the tab “GRAPHICS” to download whole PD map and the single sub maps as SVG file
  • Note: The whole PD map could be downloaded under “source file”.

Fig. 18: Export function: Screenshot shows example for ELEMENTS EXPORT. Here proteins related to Cell Death pathway were extracted. HGNC symbol and Uniport identifier were used for annotation. Note: only green coloured annotations are feasible.

Select mode

  • Enables the export of certain areas of PD map area into as model (CellDesigner xml. file) or as image (PNG, PDF)
  • Right click with the mouse in the PD map in the area you like to export.
  • Click on “Select mode” (Fig. 19).
  • Clicking around the area of interest will generate a frame (Fig. 20).
  • As soon as the frame is closed the content can be exported.
  • Clicking right mouse button within the frame (Fig. 20).

Fig. 19: Generation of a frame to define region for export

Fig. 20: Export of the selected area (grey coloured) as SBML file

  • Click on “Export as model” to download the corresponding xml file (CellDesigner SBML) or SBGN-ML file.
  • Click on “Export as image” to download an image file (png or pdf). Please note “Export to image” always generates rectangles.

Help

In case of any problems or questions regarding the PD map functionalities please contact marek.ostaszewski@uni.lu or stephan.gebel@uni.lu.

Introduction


 
PD map tutorial - Introduction and Overview - Pathways and Compartments (Part 1)

PD Map Tutorials


 
PD map tutorial - How to browse and search (Part 2)</p> <p>&nbsp;</p> <p>&nbsp;</p> <p>&nbsp;</p> <p>&nbsp;

 
Pd map tutorial - How to provide comments and feedback (Part 3)

 
Pd map tutorial - How to use drug targeting interface (Part 4)

 
PD map tutorial - How to display implemented experimental data sets (Part 5)

 
PD map tutorial - How to display custom data sets on the PD map (Part 6)

 
PD Map Tutorial - How to explore new interactions (Part 7)</p> <p>&nbsp;</p> <p>&nbsp;</p> <p>&nbsp;</p> <p>&nbsp;</p> <p>&nbsp;