The nf-core framework for community-curated bioinformatics pipelines

Ewels, Philip; Peltzer, Alexander; Fillinger, Sven; Patel, Harshil; Alneberg, Johannes; Wilm, Andreas; Garcia, Manon; Tommaso, Paolo Di; Nahnsen, Sven

doi:10.1038/s41587-020-0439-x

Cited by 1,717 publications

(1,133 citation statements)

References 20 publications

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“…Transcription factor DAP-seq and ChIP-seq DAP-seq profiles for 32 maize TFs (12, 47) (Dataset S6) were downloaded from the SRA as were ChIP-seq for 5 TFs: KNOTTED1 (KN1) (48) , RAMOSA1 (RA1) (49) , fasciated ear4 (FEA4) (50) , Opaque2 (O2) (52) , PERICARP COLOR 1 (p1) (51) . Sequencing data were downloaded from NCBI using the SRA Toolkit and processed using the nf-core ChIP-seq pipeline (91) . Briefly, reads were trimmed by Trim Galore!…”

Section: Expression Datamentioning

confidence: 99%

Stable unmethylated DNA demarcates expressed genes and their cis-regulatory space in plant genomes

Crisp

Marand

Noshay

et al. 2020

Preprint

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The genomic sequences of crops continue to be produced at a frenetic pace. However, it remains challenging to develop complete annotations of functional genes and regulatory elements in these genomes. Here, we explore the potential to use DNA methylation profiles to develop more complete annotations. Using leaf tissue in maize, we define ∼100,000 unmethylated regions (UMRs) that account for 5.8% of the genome; 33,375 UMRs are found greater than 2 kilobase pairs from genes. UMRs are highly stable in multiple vegetative tissues and they capture the vast majority of accessible chromatin regions from leaf tissue. However, many UMRs are not accessible in leaf (leaf-iUMRs) and these represent a set of genomic regions with potential to become accessible in specific cell types or developmental stages. Leaf-iUMRs often occur near genes that are expressed in other tissues and are enriched for transcription factor (TF) binding sites of TFs that are also not expressed in leaf tissue. The leaf-iUMRs exhibit unique chromatin modification patterns and are enriched for chromatin interactions with nearby genes. The total UMRs space in four additional monocots ranges from 80-120 megabases, which is remarkably similar considering the range in genome size of 271 megabases to 4.8 gigabases. In summary, based on the profile from a single tissue, DNA methylation signatures pinpoint both accessible regions and regions poised to become accessible or expressed in other tissues. UMRs provide powerful filters to distill large genomes down to the small fraction of putative functional genes and regulatory elements.Significance StatementCrop genomes can be very large with many repetitive elements and pseudogenes. Distilling a genome down to the relatively small fraction of regions that are functionally valuable for trait variation can be like looking for needles in a haystack. The unmethylated regions in a genome are highly stable during vegetative development and can reveal the locations of potentially expressed genes or cis-regulatory elements. This approach provides a framework towards complete annotation of genes and discovery of cis-regulatory elements using methylation profiles from only a single tissue.

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Section: Expression Datamentioning

confidence: 99%

Stable unmethylated DNA demarcates expressed genes and their cis-regulatory space in plant genomes

Crisp

Marand

Noshay

et al. 2020

Preprint

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“…Reads from ATAC-Seq fastq files were aligned to the mm10 genome, peaks mapped and quantified using the crickbabs/BABS-ATACSeqPE nextflow pipeline (https://github.com/ crickbabs/BABS-ATACSeqPE; git commit id: 22edccf72855d42e6692a27385cf50666c8f391c; now superseded; a newer version is available as part of the nf-core project: nf-core/atacseq pipeline (https://doi.org/10.5281/zenodo.2634132 (Ewels et al, 2020) ). The pipeline was run using nextflow version 0.30.2 (Di Tommaso et al, 2017) with the command "nextflow run main.nf --design ../design.csv --genome mm10 -profile conda --outdir ../results/".…”

Section: Atac Sequencing Analysismentioning

confidence: 99%

Extensive transcriptional and chromatin changes underlie astrocyte maturationin vivoand in culture

Lattke

Goldstone

Guillemot

2020

Preprint

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Astrocytes have diverse functions in brain homeostasis. Many of these functions are acquired during late stages of differentiation when astrocytes become fully mature. The mechanisms underlying astrocyte maturation are not well understood. Here we identified extensive transcriptional changes that occur during astrocyte maturation and are accompanied by chromatin remodelling at enhancer elements. Investigating astrocyte maturation in a cell culture model revealed that in vitro-differentiated astrocytes lacked expression of many mature astrocyte-specific genes, including genes for the transcription factors Rorb, Dbx2, Lhx2 and Fezf2. Forced expression of these factors in vitro induced distinct sets of mature astrocytesspecific transcripts. Culturing astrocytes with FGF2 in a three-dimensional gel induced expression of Rorb, Dbx2 and Lhx2 and improved their maturity based on transcriptional and chromatin profiles. Therefore extrinsic signals orchestrate the expression of multiple intrinsic regulators, which in turn induce in a modular manner the transcriptional and chromatin changes underlying astrocyte maturation.

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“…CUT&RUN data analysis. CUT&RUN data was analyzed utilizing the nf-core 46 ChIPSeq pipeline 47 using the human genome hg38 and calling peaks in broad-peak mode. Aligned reads of the individual replicates were merged using samtools v1.9 48 and RPGC-normalized tracks were calculated and plotted as composite density plots using deeptools v3.1.2 49 .…”

Section: Motif Analysismentioning

confidence: 99%

LSD1 inhibitors induce neuronal differentiation of Merkel cell carcinoma by disrupting the LSD1-CoREST complex and activating TGFβ signaling

Leiendecker

Jung

Neumann

et al. 2020

Preprint

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Merkel cell carcinoma (MCC) is a highly aggressive, neuroendocrine skin cancer that is either associated with the clonal integration of the Merkel cell polyomavirus or with chronic sun exposure 1,2 . Immunotherapy is initially effective in many patients with metastatic MCC, but the response is rarely durable 3,4 . MCC lacks actionable mutations that could be utilized for targeted therapies, but epigenetic regulators, which govern cell fate, provide unexplored therapeutic entry points. Here, we performed a pharmacological screen in MCC cells, targeting epigenetic regulators. We discovered that the lysine-specific histone demethylase 1A (LSD1/KDM1A) is required for MCC growth in vitro and in vivo. HMG20B (BRAF35), a poorly characterized subunit of the LSD1-CoREST complex, is also essential for MCC proliferation. LSD1 inhibition in MCC disrupts the LSD1-CoREST complex, directly induces the expression of key regulators of the neuronal lineage and of members of the TGFβ pathway, and activates a gene expression signature corresponding to normal Merkel cells. Our results provide a rationale for evaluating LSD1 inhibitors, which are currently being tested in patients with leukemia and solid tumors, in MCC.

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The nf-core framework for community-curated bioinformatics pipelines

Cited by 1,717 publications

References 20 publications

Stable unmethylated DNA demarcates expressed genes and their cis-regulatory space in plant genomes

Stable unmethylated DNA demarcates expressed genes and their cis-regulatory space in plant genomes

Extensive transcriptional and chromatin changes underlie astrocyte maturationin vivoand in culture

LSD1 inhibitors induce neuronal differentiation of Merkel cell carcinoma by disrupting the LSD1-CoREST complex and activating TGFβ signaling

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