Sensitive and reproducible cell-free methylome quantification with synthetic spike-in controls

Wilson, Samantha L.; Shen, Shu Yi; Harmon, Lauren; Burgener, Justin M.; Triche, Tim; Bratman, Scott V.; Carvalho, Daniel D. De; Hoffman, Michael M.

doi:10.1016/j.crmeth.2022.100294

Cited by 2 publications

(1 citation statement)

References 43 publications

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“…Transposition and amplification reactions were performed using the Nextera DNA Library preparation kit (Illumina) and sequenced 50 bp, paired-end on an Illumina NovaSeq6000 sequencer. Reads were trimmed using TrimGalore v0.6.0 with default parameters and aligned to the mm10 genome and decoy sequences, including viral sequences and cfMeDIP-seq spike-in sequences, (71,72)using bwa mem v0.7.17 (61). PCR duplicates were marked using SAMBLASTER v0.1.24 (62).…”

Section: Cutandrunmentioning

confidence: 99%

The histone lysine demethylase KDM5C fine-tunes gene expression to regulate dendritic cell heterogeneity and function

Guak,

Weiland,

VanderArk

et al. 2023

Preprint

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The functional and phenotypic heterogeneity of dendritic cells (DCs) plays a crucial role in facilitating the development of diverse immune responses that are essential for providing host protection. We found that KDM5C, a histone lysine demethylase of the KDM5 family regulates several aspects of conventional DC (cDC) and plasmacytoid DC (pDC) population heterogeneity and function. Using mice conditionally deficient in KDM5C in DCs, we found that loss of KDM5C results in an increase in Ly6C- pDCs compared to Ly6C+ pDCs. We found that Ly6C- pDCs, compared to Ly6C+ pDCs, have increased expression of cell cycle genes, decreased expression of activation markers and limited ability to produce type I interferon (IFN). Both KDM5C-deficient Ly6C- and Ly6C+ pDCs have increased expression of activation markers, however, are dysfunctional and have limited ability to produce type I IFN. For conventional cDCs, KDM5C deficiency resulted in increased proportions of cDC2Bs (CLEC12A+, ESAM-) and cDC1s, which was partly dependent on type I IFN and pDCs. Using ATAC-seq, RNA-seq, and CUT&RUN for histone marks, we found that KDM5C regulates epigenetic programming of cDC1. In the absence of KDM5C, we found an increased expression of inflammatory markers, consistent with our previous results in bone marrow-derived DCs. However, we also found a decrease in mitochondrial metabolism genes and altered expression of cDC lineage-specific genes. In response to Listeria infection, KDM5C-conditionally deficient mice mounted reduced CD8+ T cell responses, indicating that KDM5C expression in DCs is necessary for their function. Thus, KDM5C is a key regulator of DC heterogeneity by modulating the balance of DC subsets and serves as a critical driver of the epigenetic programming and functional properties of DCs.

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Section: Cutandrunmentioning

confidence: 99%

The histone lysine demethylase KDM5C fine-tunes gene expression to regulate dendritic cell heterogeneity and function

Guak,

Weiland,

VanderArk

et al. 2023

Preprint

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MEDIPIPE: an automated and comprehensive pipeline for cfMeDIP-seq data quality control and analysis

et al. 2023

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Summary Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) has emerged as a promising liquid biopsy technology to detect cancers and monitor treatments. While several bioinformatics tools for DNA methylation analysis have been adapted for cfMeDIP-seq data, an end-to-end pipeline and quality control framework specifically for this data type is still lacking. Here we present the MEDIPIPE, which provides a one-stop solution for cfMeDIP-seq data quality control, methylation quantification and sample aggregation. The major advantages of MEDIPIPE are: 1) ease of implementation and reproducibility with Snakemake containerized execution environments that will be automatically deployed via Conda; 2) flexibility to handle different experimental settings with a single configuration file; 3) computationally efficiency for large-scale cfMeDIP-seq profiling data analysis and aggregation. Availability and implementation This pipeline is an open-source software under the MIT license and it is freely available at https://github.com/pughlab/MEDIPIPE.

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Sensitive and reproducible cell-free methylome quantification with synthetic spike-in controls

Cited by 2 publications

References 43 publications

The histone lysine demethylase KDM5C fine-tunes gene expression to regulate dendritic cell heterogeneity and function

The histone lysine demethylase KDM5C fine-tunes gene expression to regulate dendritic cell heterogeneity and function

MEDIPIPE: an automated and comprehensive pipeline for cfMeDIP-seq data quality control and analysis

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