This is a supplement to: "COTRASIF: conservation-aided transcription factor binding site finder"

To verify the usability of COTRASIF's tools, and to illustrate possible uses, we performed a sample investigation of the genes of the primary response to Type I interferons.

For Type I interferons the dominating signal transduction pathway is well-studied - namely the Jak-STAT pathway, which results in the activation of ISGF3 transcription factor (interferon-stimulated gene factor), which binds specifically to ISRE (interferon-stimulated response element). Thus, searching for ISRE will yield the most probable genes of the primary response to interferon treatment.

We did the search for genes using HMM finder tool. Matrix and sequences used for search are present as examples on COTRASIF HMM task submission page: 

1 12 0 0 0 0 0 7 1 1 0 0 0 2 1
8 0 0 0 0 0 13 1 7 0 0 3 8 7 8
2 1 13 0 0 0 0 1 2 0 0 0 0 2 3
2 0 0 13 13 13 0 4 3 12 13 10 5 2 1


TAGTTTCACTTTCCC
CAGTTTCGGTTTCCC
GAGTTTCATTTTCCC
CAGTTTCATTTTCCC
TGGTTTCGTTTCCTC
AAGTTTCTATTTCCT
TAGTTTCAGTTTCAT
CAGTTTCTGTTTTGC

Search was conducted in the Rattus norvegicus promoters extracted from Ensembl release 49.

We found 338 ISREs in 323 rat genes. Literature suggests that there are up to 100-300 genes of interferon response in mammalian cells; based on this estimate, these search results were not further processed using conservation filter.

Gene lists:

  1. HMM result, as generated by COTRASIF
  2. same result in Excel format, sorted by similarity score (best-worst)
  3. same list - gene IDs only; it was used as "4. file of interesting gene list" in GOTM
  4. all rat protein-coding genes (for GOTM input field 5b)
  5. trimmed-down [3MiB] (or original [7.5MiB]) GO tree output ("export GOTree" in GOTM)
  6. 24 enriched categories: tree view
  7. 24 enriched categories: DAG view (as an image)
  8. list of genes for each GO category found to be enriched
  9. 34 genes from enriched categories, best-scoring model-similarity first

We performed enrichment analysis of 323 rat genes using GOTM. The following 24 categories were found to be enriched (13 known interferon-related underlined):

In biological process

positive regulation of signal transduction
myeloid leukocyte differentiation
positive regulation of protein biosynthesis
immune system process
immune effector process
leukocyte mediated immunity
lymphocyte mediated immunity
B cell mediated immunity
immune response
adaptive immune response
adaptive immune response (sensu Gnathostomata)
innate immune response
negative regulation of transferase activity
negative regulation of protein kinase activity
response to biotic stimulus
response to other organism
response to virus

In molecular function

monosaccharide binding
serine-type endopeptidase activity
chymotrypsin activity
enzyme activator activity
phospholipid transporter activity

In cellular component

MHC protein complex
MHC class I protein complex

© 2007 - 2008
Bogdan Tokovenko, Rostyslav Golda, Protas Oleksiy.