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 Oct, 2016).
  • 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
  • It provides hierarchical information on the cellular structures, processes and complexes.
  • Click in a compartment provides additional information in the left side information panel (“SEARCH” tab need to be active).
  • 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” (left upper side, blue panel)..

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 his original size.

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). Note: "SEARCH" tab needs to be active.

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 (Fig. 4A). First click on the element, then on the coloured number above and then the related checkbox (“Show all”) (Fig. 4B).
  • For more information on the different tools on drugs, chemicals and miRNAs interaction see related chapters 4, 5, and 6.

Fig. 4: Additional information on MARK2 displayed as pop up.

  • Clicking on a connection line (see red arrow) between species (Fig.5) provides detailed information on the underlying reaction, displayed in the left panel. This includes information on reactants and links to the underlying sources (i.e., PubMed IDs or database such as Reactome or KEGG).
  • note:"SEARCH" tab needs to be active

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

Click on “LEGEND” button (right upper side, blue panel; see blue arrow) provides details on the format of elements and interactions.

Search

  • The "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 (e.g., DJ-1 for PARK7).
  • Search for multiple elements: separate names by semicolon
  • Click 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)

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

  • Clicking on the coloured circle in the panel will direct you to the specific position of element in the PD map.
  • Clicking on the bubble pinned to the element will provide basic information on the species and additional search functionalities for proteins, genes and miRNA (see Fig. 4).
  • Clicking on “CLEAR” (right upper corner; red arrow) removes all search results.

Note: To search for specific publications and see how they are integrated in the PD map, please use the reference list at the PD map homepage reference list at the PD map homepage

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. 7) (note: if you are logged in, name and e-mail are already enterred)
  • The curation team will be notified on new comments and respond to them immediately.
  • Comment (without personal information) is visible on the PD map if “Pinned” is on “Yes”

Fig. 7: Screenshot shows the activated comment field

  • To see all pinned comments, click on the button “COMMENTS” (right upper side, blue panel).
  • Clicking on the comment icon “ ” in the PD map displays the content on top of the icon (see Fig. 8).

For tablets and smart phones:use comment button (Fig. 8) in the information panel

Fig. 8: Screenshot after activating the “COMMENTS” button (red circle), displaying position of all pinned comments. Details of comment on PGAM5 is visible after clicking on the related icon in the PD map.

How to use the drug interface

  • The “DRUG” interface allows to search for potential drug targets within the PD map (see also related blog entry: drug-target-interface)
  • Go to the “DRUG” tab
  • Type drug names, synonyms or brand names in the search field and click on the magnifier
  • 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. 9: 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) of striatal neurons. (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. 4, Fig. 11, Fig. 12).

Please note:

  • If within a multiple search several drugs hit the same element, the bubbles will overlap and only the one from the first search is visible on that element.
  • 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.
  • Note: All results are displayed simultaneously in left panel and all results are displayed simultenaeously in a pop up informaiton field when clicking on the bubble pinned to the target (see Fig. 4; Fig. 9C, Fig. 10 and Fig 11)
  • Left panel shows also targets that are not in the PD map at the end of the list (see Fig. 11)

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 (ctdbase.org).
  • Only interactions that are annotated to the disease term Parkinson’s disease (MeSH ID: D010300) in the CTD database are considered

 

  • Go to the “CHEMICAL” tab (left panel)
  • 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)
  • 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. 10: Search for the interaction targets of “hydrazine” and “rotenone”. Information panel displays information on “hydrazine”. Interacting species are labelled in the map (blue bubbles for hydrazine; green bubbles for rotenone). Clicking on framed number above the target (e.g., blue 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. 9C, and Fig 11)

Please note:

  • If within a multiple search several chemicals hit the same element, the bubbles will overlap and only the one from the first search is visible on that element.
  • 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.
  • Note: All results are always displayed in a left panel and all results are displayed simultaneously in a pop up information field when clicking on the bubble pinned to the target (see Fig. 4; Fig. 9C, Fig. 10 and Fig 11)
  • Left panel shows also targets that are not in the PD map at the end of the list (see Fig. 11)

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.

 

  • Go to the “MiRNA” tab (left panel)
  • Type in the miRNA ID; you need to use 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 chemical and the potential targets, including links to miRTarBase and PubMed is provided in the left panel.

Fig. 11: Search for targets of hsa-miR-125a-3p. Left panel displays information on hsa-miR-125a-3p and its targets. Targeted species are marked by pinned bubbles (green triangles). 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 a target that is not in the PD map (here GPC4).

Please note:

  • If within a multiple search several chemicals hit the same element, the bubbles will overlap and only the one from the first search is visible on that element.
  • 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.
  • Note: All results are always displayed in the left panel and all results are displayed simultaneously in a pop up information field when clicking on the bubble pinned to the target (see Fig. 4; Fig. 9C, Fig. 10 and Fig 11)
  • Left panel shows also targets that are not in the PD map at the end of the list (e.g. GPC4 in Fig. 11)

How to display implemented experimental 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. green:stronger expression in aged brain; red:lower expression in aged brain. See also: 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. green:stronger expression in PD; red: lower expression in PD. See also: Fujita et al., 2013.
    • PD UK GO Project genes: Genes annotated by the Parkinson's disease GO Annotation Project. Yellow (beige): high priority gene list, blue (turqouise): Parkinson's - relevant protein. See also: 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 on the magnifier under “View” to display the respective data set on the PD map.
  • Pathway and compartment view provides an overview on cellular processes relevant to visualized data (Fig. 12)
  • Detailed differential expression (green rectangle: up = red rectangle = down) is best visible using the colourless overlay “Empty” (Fig. 13).

Fig. 12: Overlay of the PD substantia nigra data set to the PD map.

  • Displaying multiple data set is possible by ticking checkboxes in the “View” column. Results from different data sets are simultaneously displayed by subdivided coloured rectangles (Fig. 13)
  • Additional information is provided when clicking on the species (Fig. 13: NR4A2)

Fig. 13: Overlay of PD substantia nigra data set, ageing brain data set and PD UK GO genes to the PD map. Clicking on NR4A2 provided detailed information in a pop up box. In addition information on interacting drugs, chemical or microRNA can be requested here (see Chapters: 4, 5, and 6).

How to display custom data sets on the PD map

  • Request for a free account is mandatory
  • Click on the “LOGIN” tab (next button right from "OVERLAYS", click n the arrowhead in the "OVERLAYS" tab to go there) and then on “Request an account”.
  • User name and password will be provided by e-mail.
  • After login, a new tab “PROFILE” displaying user specific data
  • To upload own data sets, click on the “OVERLAYS” tab. This opens the menu for data set upload and management (“USER-PROVIDED OVERLAYS”)
  • The account enables the upload of 100 separate data sets
  • All uploaded data are accessible by the system administrators due to technical reasons, but they are not visible by any other user

Data preparation

  • For upload to PD map, data needs to be transformed in 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 genes 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 transformed into a range between -1 to 1 (see Fig. 14).
  • To just display a list of genes or proteins without differential expression, assign the value 1 to all HGNC gene names. Related genes/proteins will be finally coloured in green.

 Fig. 14: txt.file for upload, containing two columns with HGNC name and normalized value (between -1 and 1).

Data upload

  • Click on "OVERLAYS" tab (left panel)
  • Click on “Choose” and select a data set (.txt file)
  • Enter a name for the data set in the “ADDING” field.
  • Click on “GENERATE” starts the data processing.
  • Blue information box shows correct process (Fig. 15A)
  • Red information box displays potential failures in the process (Fig. 15B)

Fig. 16: Data upload process information. Left side: File processed successfully. Right side: Data upload failure notification: Error! At least two rows try to set colour to element: SLC1A1.

After successful processing a report will be sent by e-mail to the user. It contains the uploaded data including values and matches on the PD map (Fig. 16).

Fig. 16: Process report, includes a list of uploaded data with information on the particular elements (i.e., name, value and matches in the PD map, see enlargement).

Data visualisation

  • Under “USER-PROVIDED OVERLAYS” check the box under “VIEW” for those data sets that should be displayed on the PD map..

Fig. 17: Custom data set display (section view of the PD map).

  • Elements are automatically coloured by the following colour codes in accordance to their dedicated values

 

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. 18).

Fig. 18: Custom test data set displayed on the PD map together with PD substantia nigra dataset from general layout. Clicking on element provides additional information and search functionalities.

In general, all PD map elements can be individually coloured on the PD map. If you like to colour elements individually please contact us directly.

Submaps

  • To maintain overall structure of the PD map, some parts of the main network were displayed in separate, more detailed submaps (see also blog entry from Oct 2016: mapupdate-october-16-edition).
  • The submaps are fully operational; i.e., search functions and data display work simultaneously on the whole PD map and on the submaps.
  • Enter submaps by clicking the "SUBMAPS" tab which is right from “OVERLAYS” (click onarrowhead in the “OVERLAYS” tab to go there) (see Fig.19).
  • Click on magnifier to enter a receptive submap.
  • Alternatively you may click on dedicated elements in the map while having "SEARCH" tab active.
  • Search directly for submap term such as “Gene Ontology genes” or “Iron metabolism” inthe “SEARCH” function.

Fig. 19: Display of the Iron metabolism submap

How to export parts of the PD map

Export function

  • “EXPORT”button (left lower corner) opens a new window.

Fig. 20: Export function: red arrow shows the location of the “EXPORT” button.

  • Use the tab “ELEMENT EXPORT” to select specific elements for download.
  • Note: you can download the whole PD map on the homepage under “downloads

 Fig. 21: Export function: Screenshot shows example for ELEMENTS EXPORT. Here proteins related to Apoptosis 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 (xml or sbgn 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” (red arrow Fig. 22).
  • Clicking around the area of interest will generate a frame.

Fig. 22: Generation of a frame to define region for export

  • As soon as the frame is closed the content can be exported.
  • Clicking again right mouse button.

Fig. 23: Export of the selected area (grey coloured) as image.

  • Click on “Export as model” to download the corresponding xml or sbgn file (Fig. 22).
  • 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;