PsychENCODE GRN questions

Q1:
I had a few questions about the Gene Regulatory Networks published as part of the Comprehensive functional genomic resource and integrative model for the human brain at http://resource.psychencode.org/. Could you pass these along to whomever is best suited to address them?

First question: Which reference genome is used?

The GRN has the following format:

Transcription_Factor,Target_Gene,Enhancer_Region,Edge_Weight

And most rows look like:

BARHL2,SHC1,chr1:154869072-154870071,0.284806116416629

however, some rows just have "Promoter" in the Enhancer_Region column, like this one:

NR2F2,SHC1,Promoter,0.120934147846037

But since NR2F2 (and most other genes) have a couple different reference haplotypes in both refseq and gencode (e.g. see NR2F2 in UCSC genome browser), it’s ambiguous to me where "Promoter" designates.

Does there exist a version of the GRN with Promoter substituted for chromosomal coordinates, or would you mind sending a reference to the haplotype you used as reference when building this GRN?

To summarize above: what reference genome did you use in constructing the GRN? What region does "Promoter" evaluate to?

A1:
We defined the promoter regions by a window of ±1.25 kb (=2.5 kb in
total) relative to the transcription start site (TSS) on hg19.

Q2:
Could you send the hg19 reference genome you’re referring to?

If I go to the UCSC browser and look at refseq hg19, for some arbitrary gene: [[see image]]

The gene has multiple reference isoforms. Where does your GRN situate the promoter for this gene? i.e. which chromosomal location does the ChIP track you integrated in your GRN identify the TF at? Chromosomal coordinates would be less ambiguous than stating the TF binds the promoter. Would the production of such a network be possible, or would you be able to send us a reference genome you used with a single location for each promoter (i.e. a single tss)? How did you choose the ‘canonical’ isoform for each gene? What about the promoters upstream of the other tss’s — is there evidence of regulation at those alternate promoters?

Any chance you might be able to resolve this for us? It seems to limit the utility of this network to have this ambiguity about the chromosomal location of these transcriptional regulatory events. It would be a shame not to resolve it, I think.

A2:
I have added the promoter TSS file to our website at: http://resource.psychencode.org/Datasets/Integrative/tss.sites.codingOnly.gencode.v19.annotation.bed

It can be found at resource.psychencode.org by navigating to the section on "Integrative Analysis", and scrolling to item 3.

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