Package: pegs
PEGS(Peak-setEnrichment ofGene-Sets) is
a Python bioinformatics utility for calculating enrichments of gene
clusters at different genomic distances from peaks.Free software: 3-Clause BSD LicenseDocumentation:https://pegs.readthedocs.io/en/latest/Code:https://github.com/fls-bioinformatics-core/pegsQuick StartIt is recommended to installPEGSviapipin a virtualenv,
for example:% virtualenv venv.pegs
% source venv.pegs/bin/activate
% pip install pegsThis will provide thepegsandmk_pegs_intervalsprograms.Alternatively you can installPEGSinto a Conda environment,
for example:% conda create -c bioconda -c conda-forge -n pegs pegsThe simplest use ofPEGSis:pegs GENE_INTERVALS --peaks PEAKS1 [PEAKS2 ...] --genes CLUSTERS1 [CLUSTERS2 ...]whereGENE_INTERVALSis a set of reference transcription
start sites (TSSs) for all genes,PEAKS1...Nare one or more
BED files with peak-sets, andCLUSTERS1...Nare one or more
files defining gene clusters.This will output a PNG heatmap and an XLXS file with the
p-values and gene counts from the enrichment calculations.Full documentation can be found at:https://pegs.readthedocs.io/en/latest/LicensingPEGS is licensed under the 3-Clause BSD License.Example: Mouse glucocorticoidal datasetThanks to Louise Hunter for providing this example.An example application ofPEGSis the analysis of up- and
down-regulated glucocorticoidal targets from an RNA-seq study
of liver samples from mice treated acutely with dexamethasone
or vehicle (Carattiet al.2018), combined with corresponding
GR ChIP-seq and chromatin accessibility data (DNase I
hypersensitive (DHS) regions) (Grontvedet al.2013 and
Sobelet al.2017 respectively), and mouse liver TAD
boundary data (Kimet al.2018).The files for these datasets are available here:RNA-seq data:1_zt6up.txtand2_zt6down.txtChIP-seq and chromatin accessibility data:Grontved_GR_ChIP.bedandZT6_DNase.bedTAD boundary data:mESC-TADs_mm10.txtThePEGSanalysis was performed on these data using the
command:pegs mm10 \
  --peaks data/peaks/*.bed --genes data/clusters/*.txt \
  -t data/mESC-TADs_mm10.txt \
  -d 1000 5000 10000 50000 100000 200000 500000 1000000 5000000The resulting output files (XLSX and heatmap) can be found here:glucocorticoid_heatmap.pngglucocorticoid_results.xlsxThe analyses indicate a strong association of dexamethasone
up-regulated genes with dexamethasone-induced GR peaks at
distances up to 500kbp from these peaks, but no evidence of
down-regulated genes - indicating distinct mechanisms of gene
activation and repression by glucocorticoids. At the same time,
there is promoter proximal enrichment for both up-andReferencesCaratti, G.et al.(2018) REVERBa couples the clock to hepatic
glucocorticoid action.J Clin Invest128(10):4454-4471Grontved, L.et al.(2013) C/EBP maintains chromatin accessibility
in liver and facilitates glucocorticoid receptor recruitment to
steroid response elements.EMBO J32(11), 1568-83Kim, Y.H.et al.(2018) Rev-erbα dynamically modulates chromatin
looping to control circadian gene transcription.Science359(6381):1274-1277Sobel, J.A.et al.(2017) Transcriptional regulatory logic of the
diurnal cycle in the mouse liver.PLoS Biol15(4): e2001069AcknowledgementsThanks to Louise Hunter for providing the mouse glucocorticoidal
example, and to Kyle Pollina for allowing us to use thepegsname on the Python Package Index.