PolyDoms: Case Studies


CASE STUDY 1:

Using the gene ontology to create a coding-SNP set.
Query: To obtain a list of human genes that are associated with gene ontology term "protein ubiquitination"

  1. From the homepage, click on the "Ontology Selector" (under section "Search by disease, gene ontology, pathway, or gene family").
  2. A new window ("Search for Gene Ontology") opens up. Enter the search term "ubiquitination" and hit "Search".
  3. Highlight the term "protein ubiquitination" from the search results window and hit "Use these ontologies for search" button to populate the "Gene ontologies already selected" window. click "Done" to return to the PolyDoms query page.
  4. Hitting the "Search" button without selecting any of the "Filter Options" will return the human genes (81 proteins, 39 unique in the current version) associated with the gene ontology "protein ubiquitination". At this stage, users can either download the results as a spreadsheet by clicking on the link "Download the results" or proceed to view the nonsynonymous or synonymous model of each of the protein
  5. Alternately, use the "Filter options" to refine the query. For e.g., from the "Filter options" select "Occurring in domain", "Deleterious nsSNP", "Damaging nsSNP", and Interaction and hit "Search". This will return 19 proteins (7 unique), each of which has at least one nsSNP that occurs in a conserved domain and has been predicted as "Deleterious/Damaging" by SIFT/PolyPhen, and is known to interact with other proteins.

 

CASE STUDY 2:

Using the gene family to create a coding-SNP set.
Query: To obtain a list of human genes that belong to the gene family "Annexins".
  1. From the homepage, click the gene family and select "Annexins". Then click "Search" button.
  2. A query without any filters returns 19 sequences (12 unique; 5 have isoforms).
  3. If the filters "occurring in domain", "deleterious" and "damaging" are selected and searched again, it returns 5 sequences (4 unique ANXA2, ANXA3, ANXA7 and ANXA9), each of which has at least one nsSNP predicted as intolerant by both SIFT and PolyPhen analysis and the variant residue is part of the annexin repeat domain.

 

CASE STUDY 3:

Using pathways to investigate the SNP-pathway relationships.
Query: To obtain a list of human genes involved in the "apoptosis" pathway
  1. From the homepage, click on the "Pathway Selector".
  2. A new window ("Search for Pathways") opens up. Enter the search term "apoptosis" and hit "Search". Highlight the term "Apoptosis (Kegg)" from the search results window and hit "Use these pathways for search" button to populate the "Pathways already selected" window. Click "Done" to return to the PolyDoms query page.
  3. Hitting the "Search" button without selecting any of the "Filter Options" will return the human genes (175 proteins, 97 unique in the current version) associated with the pathway "apoptosis". At this stage, users can either download the results as a spreadsheet by clicking on the link "Download the results" or proceed to view the nonsynonymous or synonymous model of each of the protein
  4. Alternatively, use the "Filter options" to refine the query. For e.g., from the "Filter options" select "Occurring in domain", "Deleterious nsSNP" and "Damaging nsSNP" and hit "Search". This will return 45 proteins (35 unique), each of which has at least one nsSNP that occurs in a conserved domain and has been predicted as "Deleterious/Damaging" by SIFT/PolyPhen.