KnowYourCG: Facilitating Base-Level Sparse Methylome Interpretation

KnowYourCG (KYCG) is a data interpretation framework for functional DNA methylation analysis. Unlike existing tools that target genes or genomic intervals, KYCG features direct base-level screenings of diverse biological and technical influences, including sequence motifs, transcription factor binding, histone modifications, replication timing, cell-type–specific methylation, and trait associations. Through efficient infrastructure that rapidly screens thousands of knowledgebases, KYCG addresses data sparsity in low-pass or single-cell DNA methylomes, 5-hydroxymethylation (5hmC) profiles, spatial DNA methylation maps, and array-based datasets for EWAS.

KnowYourCG v2

This Bioconductor package is KnowYourCG v1, and stays on the 1.x series. KnowYourCG v2 is kycg: the same framework rewritten in C directly on YAME's bit-packed CpG formats, run from the command line rather than from R.

conda install -c zhou-lab -c conda-forge kycg yame

Documentation: https://zhou-lab.github.io/kycg/

Try it online, no install: https://zhouserver.research.chop.edu/knowyourcg/

v2 fetches and verifies its own knowledgebases and screens genome-wide sets without R; its statistics are validated against this package. Use whichever fits your pipeline — v1 if your analysis lives in R and Bioconductor, v2 for command-line and large sequencing work.

Citation

Goldberg DC, Fu H, Atkins D, Moyer E, Lee CN, Deng Y, Zhou W. KnowYourCG: Facilitating base-level sparse methylome interpretation. Science Advances 11(43): eadw3027 (2025). https://doi.org/10.1126/sciadv.adw3027

Install knowYourCG

Release version can be installed from Bioconductor

BiocManager::install("knowYourCG")

Development version can be installed from github.

BiocManager::install('zhou-lab/knowYourCG')

The vignettes also load SummarizedExperiment, sesame and gprofiler2, which BiocManager::install("knowYourCG") does not fetch. To run every example:

BiocManager::install(c("knowYourCG", "SummarizedExperiment", "sesame",
                       "gprofiler2"))

Main Functions

Enrichment Testing

testEnrichment - Test for enrichment of query in knowledgebase sets
testEnrichment2 - Test enrichment from YAME-compressed CG sets
testEnrichmentSEA - GSEA-like test for association of categorical variable against continuous variable
testProbeProximity - Test if query probes share closer genomic proximity than random
aggregateTestEnrichments - Aggregate test enrichment results

Database Management

getDBs - Get databases by full or partial names
listDBGroups - List database group names
loadDBs - Load knowledgebase databases from TSV files
buildGeneDBs - Build gene-probe association database
dbStats - Aggregate methylation over database set features
annoProbes - Annotate Probe IDs using KYCG databases

Visualization

KYCG_plotBar - Bar plot of most enriched CG groups
KYCG_plotDot - Dot plot of most enriched CG groups
KYCG_plotEnrichAll - Plot enrichment test results
KYCG_plotLollipop - Lollipop plot of log(estimate)
KYCG_plotManhattan - Manhattan plot for EWAS results
KYCG_plotMeta - Plot meta gene or other meta genomic features
KYCG_plotMetaEnrichment - Plot meta gene enrichment
KYCG_plotPointRange - Point range plot for enrichment results
KYCG_plotSetEnrichment - Plot set enrichment
KYCG_plotVolcano - Volcano plot of -log2(p.value) vs log(estimate)
KYCG_plotWaterfall - Waterfall plot of log(estimate)

Data Access

kycgDataCache - Cache KnowYourCG data
kycgDataGet - Get KnowYourCG data

Utilities

linkProbesToProximalGenes - Find genes in genomic proximity to Infinium probes
bedToCg - Convert BED CpG set to YAME .cg format