...find genes/diseases identifiers?

Select the identifiers to execute a query in PhenUMA. Severals resources are available to find the gene or disease of interest: NCBI , Ensembl, OMIM , HGNC and Orphanet.

..manage the interface?

The visualizer allow to interact with the network. Some controls are located in the left-hand panel: filters, check phenotypic information of the selected nodes, enrichment analyses...

...download the output data?

Resulting networks can be downloaded in text file format. This makes it possible to work with the results using other platforms as Cytoscape.

...visualize resulting networks using Cytoscape?

Text files returned by PhenUMA can be used in Cytoscape. This video tutorial shows how to visualize PhenUMA networks using this tool.

1 Select "Network" option

2 Select the input type: genes, OMIM diseases, Orphan diseases or Phenotypes

3 Write your query

Introduce a list of genes, diseases or phenotype separate by commas:

• For queries of OMIM genes/diseases use the OMIM id (i.e. 271980), the Orphan id (i.e. 95) for Orphan Diseases and the HPO id for phenotypes (i.e. HP:0001691, HP:0003116, HP:0001953). As long as you want to introduce a set of genes you can use the EntrezGene (Recommended), Symbol or Ensembl. The MIM, HGNC and Orpha ids are allowed too but, it must be indicated in the same way: MIM:300461, HGNC:8512 or ORPHA:124033.

4 Select the output network

Select the network that you want to visualize.

5 Choice the confidence level

Three leves of confidence are availiable. Select a high to get a network with the more significative relationships. If you want to lower the threshold select a medium or low confidence.

6 Press "Execute" button and wait some seconds while the query is performed.

Once the network has been generated the table/visualizer view will be shown.

1 Select "Enrichment Analysis" option

2 Select the input type: genes, OMIM diseases, Orphan diseases

3 Write your query

Introduce a list of genes, diseases separated by commas:

• For queries of OMIM genes/diseases use the OMIM id (i.e. 271980), the Orphan id (i.e. 95) for Orphan Diseases and the HPO id for phenotypes (i.e. HP:0001691, HP:0003116, HP:0001953). As long as you want to introduce a set of genes you can use the EntrezGene (Recommended), Symbol or Ensembl. The MIM, HGNC and Orpha ids are allowed too but, it must be indicated in the same way: MIM:300461, HGNC:8512 or ORPHA:124033.

4 Select type of analysis

Select the network that you want to execute.

The avaliable enrichment analyses are:

• Phenotypic (HPO)
• Functional (GO Biological Process)
• Functional (GO Cellular Component)
• Functional (GO Molecular Function)

5 Press "Execute" button and wait some seconds while the query is performed.

Once the network has been generated the enrichment table will be shown.

Genes

EntrezGene/GeneID is the indentifier recommend for queries of genes in PhenUMA. 1411, 2629, 3845, 208

However, others identifiers are supported: Gene Symbol speciffically the official symbol provided by HGNC, Ensembl, HGNC id, MIM and Orpahnum. Visit http://www.ncbi.nlm.nih.gov/ , www.genenames.org , http://www.ensembl.org/index.html or http://www.orpha.net/ to find the identifiers of your genes.

Gene Symbols

Important! If you choose HGNC, MIM or Orphanum identifiers you must indicate the database of reference (i.e MIM:123610, HGNC:2394 or ORPHA:120836) to avoid confusion.

Different identifiers:

OMIM Genes/Diseases

For queries of OMIM genes or diseases a list of MIM id must be provided:

Visit www.omim.org to find the identifier of your disease(s) of interest.

Orphanet Diseases

Use orphanum identifier:

Visit www.orpha.net to find the identifier of your orphan disease(s) of interest.

Phenotypes

Use HPO id identifier:

Visit http://compbio.charite.de/phenexplorer/ to find the identifier of your phenotype of interest.

Read more about identifers in Inputs.pdf

Gene-Gene

Genes networks can be built from a list of genes or diseases (OMIM diseases or Orphan diseaes). If a list of diseases (yellow circles) is provided the relationships between genes and diseases, obtained from OMIM and Orphanet, are used to create a list of input genes (red triangles). Seed network includes relationships between the input genes and the rest of genes of the knowledge base. The type of relationship of seed network is the selected by the user: Gene-Gene Semantic Similarity from HPO, Gene-Gene Semantic Similarity from GO, etc. Finally, the network is extended with the rest of relationships among genes included in PhenUMA: phenotypic (HPO), functional (GO), protein-protein interactions (STRING), metabolic (Veeramani et al.) and inferred relationships.

OMIM Disease - OMIM Disease / Orphan Disease - Orphan Disease

The procedure used to generate diseases networks is similar to genes network workflow. The following figure represents OMIM diseases (yellow circles in PhenUMA) networks but could be extrapolated to Orphan diseases (blue octogons in PhenUMA) networks. Extended network includes phenotypic and inferred relationships among diseases.

Phenotypic Query Network

In this type of networks the input list of phenotypes is considered a phenotypic profile and is compared with the rest of genes or diseaes (OMIM or Orphanet). The rest of the steps are similar to the rest of networks.