Tutorial

Contents 1 Introduction 2 Preliminary steps 3 Browsing by Gene 3.1 Searching for an interest gene 3.2 Description of the different parts of a gene page 3.2.1 Pie charts 3.2.2 Synopsis 3.2.3 External references 3.2.4 Known phenotypes 3.2.5 Protein interaction network 3.2.6 Patients reports 3.2.7 Mutations and translocations 3.3 Different ways to edit the gene informations 3.3.1 Edit the basic informations (Synopsis) of the gene 3.3.2 Editing the phenotypes associated to a gene 3.3.2.1 Add a new CHD phenotype 3.3.2.2 Remove or edit a phenotype 3.3.2.3 Defining a new reference 3.3.2.4 Add a study reference 3.3.2.5 Remove or edit a study 3.3.3 Add, remove and modify a translocation 3.3.4 Add a mutation 3.3.5 Remove or modify a mutation 3.4 Addition a new CHD related gene in the repository 4 Browsing by Congenital Heart Defect (CHD) 4.1 Searching for a CHD of interest 4.2 Description of the different parts of a CHD page 4.2.1 Chromosome map 4.2.2 Pie chart 4.2.3 Summary 4.2.4 List of genes 4.2.5 Regions and translocations associated to a pathology 4.2.6 Patients reports 4.3 Edit and modify CHD informations 4.3.1 Modifying the synopsis information 4.3.2 Adding / removing / modifying a gene-phenotype association 4.3.3 Adding / removing / modifying a study 4.4 Modify / remove / add a linkage region

[edit] Introduction

This tutorial will guide you through the CHDWiki describing some of its most popular and useful applications and how to achieve the main tasks in the Wiki.

[edit] Preliminary steps

This tutorial assumes you have been registered to CHDWiki according to the procedure described here.

[edit] Browsing by Gene

The CHDWiki repository contains manually curated data that were added after an extensive literature search and by expert of the fields.

[edit] Searching for an interest gene

There are two ways to look if a given gene is included in our database.

1. Typing the name of the gene in the Search field on top of the window. You can both use the EnsemblId or the Hugo usual name.
2. Running through the list of CHD related gene encoded in our database by clicking on the Browse by gene link on the left menu in the CHD section.

[edit] Description of the different parts of a gene page

In this section, we will describe the different types of information that are designed for a gene recorded in the CHDWiki.

[edit] Pie charts

The pie charts display the proportion of (syndromic or non syndromic) CHD associated to the gene of interest. For example, in the following chart, in our data, a alteration of the interest gene accounts for 52.57% in a ASD (Atrial septal defect).

[edit] Synopsis

This part contain a short description of the gene.

[edit] External references

This part contain links to the given gene in other well known databases.

[edit] Known phenotypes

This section is divided into two parts depending if the described phenotypes are syndromic or not. For each phenotype that is specified (each phenotype corresponding to a CHD in the AEPC nomenclature), the list of references where this gene - phenotype association has been described is available. Moreover, the incidence and the individual syndroms are reported. When two or more independent reports describe the same phenotype for a given gene gene, this association is considered as confirmed. You can visualize the list of publications by clicking on the show link at the bottom of the phenotype frame (circled in red).

[edit] Protein interaction network

This part represents in a graphical way the interactions between the proteins that interact with the interest protein according to various reference databases (BioGRID, MINT, etc). Proteins are represented by nodes in this network and a pairwise interaction between to proteins is represented by an edge. Green nodes represent proteins that are encoded by a gene known to be implied in CHD. The selected node is yellow.
This frame is interactive. By clicking and moving a node will change the layout of all the nodes linked to this node.

[edit] Patients reports

CHDWiki is linked to bench a repository of medical cases. In this section, you get the list of patients of the bench database presenting an alteration in the gene of interest as well as its symptoms.

[edit] Mutations and translocations

Finally, we display each individual mutation or translocation of the gene of interest that lead to a given CHD, detail it and add the references.

[edit] Different ways to edit the gene informations

[edit] Edit the basic informations (Synopsis) of the gene

Click on Edit on the top of the page or on the right of the Synopsis field. You will be automatically redirected to an edition page where you can enter your modifications.
Once your modifications are completed, you may describe the modification you entered in the Summary field (bottom of the page) and click on Save page to save the changes. Note that it is always better to re-read carefully your modifications by clicking on the Show Preview button. You will be then redirected to a page allowing you to visualize the page with your modifications. Once you visualized that your results are OK, click Save page at the bottom of the pre-visualization page.

[edit] Editing the phenotypes associated to a gene

There are four things that you can do.

1. Add a new CHD phenotype (either syndromic or non syndromic) that is observed when the gene is affected.
   
2. Modify / delete an existing phenotype
3. Add the reference of a study in order to confirm a phenotype that is already annotated in the database. This study must report the number of patients in which the mutation in the gene and the phenotype association is observed.
4. Modify / delete a study reference.

[edit] Add a new CHD phenotype

At the end of the list of described phenotypes, click on Add another phenotype. You are then redirected to the following form.

In this form, complete you have to complete the fields that way.

• Support : unconfirmed (only a single case report) / likely (two or more cases) / confirmed (two or more independant reports presenting > 1% of incidence)
• Phenotype : must be a phenotype name of the phenotypes list described here (in letters, not the category).
• Gene : Already completed as you went to this form starting from a page record. If you wish to add a new phenotype for a new gene, please follow the steps described here.
• References : all the pubmed identificators (id) related to the gene-phenotype associations. Each pubmedid must be separated by a pipe (|) character. Note that it is then interesting to enter this reference in the list of reference stored on the Wiki (tutorial TBW).
• Inheritance/Syndrome : brief description of the syndrome
• Incidence : description of the incidence
• Comments: any comments you might have

Once the changes have been made, click on the Save button at the end of the form.

[edit] Remove or edit a phenotype

Click on the pencil icon just next a phenotype window. You are then redirected to a window similar to the one described in the previous section. However, in this case, it is prefilled with the values already present in the database.

• To remove this gene-phenotype association, simply click on the Delete button at the end of the form.
• To edit the phenotype association, modify the fields and click on the Save button.

[edit] Defining a new reference

If you entered a new reference in the previous step (either by creating or editing a gene-phenotype association) and if this reference had not been previously entered in the wiki, you should see the pubmedid followed by (unspecified or mispecified) in the list of references. By clicking on the pencil icon just next to this reference, you can add this reference in the CHDWiki. In this case, you are redirected to this form.

In this form, you can fill the following fields:

• PubmedID
• Type of article
• Title of the article
• Authors
• Journal
• Year
• Abstract
• Link to abstract
• Link to full text
• Any comments

[edit] Add a study reference

First check whether the study you would like to add is not already in the database by clicking on the +show link (as described above). To add a new study, click on the Add another study link at the bottom of the gene-phenotype frame. You will be redirected to this form.

In this form, you have to specify

• the type of study (case or family report)
• the number of patient tested
• the number of mutations observed that gave the associated phenotype
• the pubmed id of the reference
• any comments

Once it is done, click on the Save button at the end of the form.

[edit] Remove or edit a study

Click on the pencil icon just next to a study. You are then redirected to a window similar to the one described in the previous section. However, in this case, it is pre-filled with the values already present in the database and there is a link at the bottom to Add the mutations details described in the study (circled in red).

• To remove this study, simply click on the Delete button at the end of the form.
• To edit this study, modify the fields and click on the Save button.

[edit] Add, remove and modify a translocation

Click on the pencil icon next to the translocation you want to modify or click Add another translocation. You obtain the following form.

On this form, you are requested to fill the following fields.

• The phenotype (respectcing the AEPC nomenclature)
• The region that is translocated
• The references
• The OMIM corresponding identificator
• Any comments

Click on the Save button once you have entered the translocation. To delete the translocation, click on the Delete button.

Note that if you added a new mutation whose Pubmed ID is not defined in the CHDWiki, you can edit the reference field as shown above (#Defining a new reference).

[edit] Add a mutation

Adding a mutation is somewhat more tricky as in our database, mutation are linked to gene-phenotype associations via studies. For this reason, to add a mutation in the mutation table, you need to edit a mutation study (as shown above) or add it and edit it. When redirected to the form shown here, click on the Add mutations details link at the bottom of the form. You will be redirected to the following form.

In this form, you can specify the following fields.

• Mutation in term of nucleotides according to the nomenclature defined at the Genome Variation Society.
• Mutation in amino acids
• Features (remarks)
• Is the mutation dominant, recessive or X-linked?
• Is the mutation familial or sporadic?
• Genetic evidences
• Study result
• Functional studies result of the mutation
• In silico predictions of the mutation
• Any comments

Click on the Save button once you have entered the mutation details.

[edit] Remove or modify a mutation

Click on the pencil icon next to the mutation you want to modify. You obtain the following form.

In this form, you can modify the fields described above. Click on the Save button once you have modified the mutation details. To delete the mutation, click on the Delete button. 

[edit] Addition a new CHD related gene in the repository

To this, click on the link Add gene in the left menu in the section Contribute. You will be redirected to a gene-phenotype association form (as described here). You can then follow the instructions described in that section.

[edit] Browsing by Congenital Heart Defect (CHD)

In this section, we will describe the kind of data contained in the CHDWiki for each CHD.

[edit] Searching for a CHD of interest

There are two ways to look if a given gene is included in our database.

1. Typing the name of the CHD in the Search field on top of the window.
2. Running through the list of CHD encoded in our database by clicking on the Browse by CHD link on the left menu in the CHD section. Note that there are CHD for which no information is available in the database (red links).

[edit] Description of the different parts of a CHD page

[edit] Chromosome map

The first feature of the CHD report page is a minimized chromosome map (red frame on the above figure) describing where on the chromosome is located each type of genetic alteration that causes the CHD. Clicking on the map will maximize it. Colored bars at each side of the chromosomes correspond to the genetic alterations. Running with your mouse on the bars will display a pop-up window with supplementary information on this particular alteration.

• On the left of the chromosomes, in pale orange, the genes whose mutation induce the CHD are represented. Running with the mouse pointer on it will give you the other CHD a mutation in this gene has been reported to induce as well as the degree of reliability of this gene - CHD association (color code from blue (no good correlation) to green (confirmed)).
• On the right of the chromosome (from left to right)
  • Pale orange arrows indicate translocations.
  • Blue lines indicate chromosomal regions implicated in a CHD.
  • First red lines indicate chromosomal gain implicated in the CHD according to the CHDWiki annotators.
  • First green lines indicate chromosomal loss implicated in the CHD according to the CHDWiki annotators.
  • Pale red lines indicate chromosomal gain implicated in the CHD according to Van Karnebeek and Hennekam (1999)
  • Pale green lines indicate chromosomal gain implicated in the CHD according to Van Karnebeek and Hennekam (1999)

You can completely customize the chromosome map by adding or removing chromosomes on the map (basically, only chromosomes where a CHD related alteration has been annotated are displayed) or adding or removing chromosomal features by clicking on the Show map controls link above the map.

[edit] Pie chart

This pie chart (blue frame) shows on all patients having the CHD of interest, the proportions of cases for which a given gene is affected (blue frame).

[edit] Summary

After the chromosome map and the pie chart, a small text may follow describing the major features of the CHD (orange frame).

[edit] List of genes

The list of gene implied in the syndromic and non syndromic CHD then follows. For each gene annotated in the Wiki, there is a short description of the paper describing the association between the CHD and the gene. This part is in fact the counter-part at the gene point of view of the known phenotypes list when looking at one given gene in the Wiki.

[edit] Regions and translocations associated to a pathology

The two next sections contain the list of chromosomal regions and translocations annotated in the database and that are associated to the CHD.

[edit] Patients reports

The CHDWiki is linked to Bench, a repository of medical cases. In this section, you get the list of patients of the Bench database presenting the CHD of interest.

[edit] Edit and modify CHD informations

[edit] Modifying the synopsis information

To modify or add the synopsis information, simply click on the Edit link on the top or at the right of the page.

[edit] Adding / removing / modifying a gene-phenotype association

At the end of the list of described genes (either after syndromic or non syndromic), click on Add another gene. You will be redirected to the form already described here. Follow the instruction of that section, the only difference lying in the fact that you will have to fill in the field with the name of the gene (and not the id of the phenotype anymore).

To edit or remove a gene phenotype association, click on the pencil icon just next to the name of the gene. You are then directed to a preform fill that can then modify freely and save by clicking on the Save button or delete by clicking on the Delete button.

[edit] Adding / removing / modifying a study

This is pretty similar to what we described before. To edit or remove a study, click on the Show link in the gene frame and then on the pencil next to the description of the study you want to edit.

To add a study, click on Add another study at the end of the gene frame.

[edit] Modify / remove / add a linkage region

As usual, to modify or remove a linkage region, click on the pencil icon next to the linkage region you want to modify (first column of the table, the pencil of the second reference is there to edit the reference properties).

To add a new region, click on the Add another region link at the end of the table.

You will be redirected to this form, pre-filled or not depending on the fact you are editing or adding a new region. You are invited to fill or modify the following fields in this form.

• Phenotype (the name of the CHD as defined here )
• Region (the coordinates of the identified region).
• References
• Number of patients presenting the CHD
• the OMIM id
• any comments