pyGenomeTracks: reproducible plots for multivariate genomic datasets

Lopez-Delisle, Lucille; Rabbani, Leily; Wolff, Joachim; Bhardwaj, Vivek; Backofen, Rolf; Grüning, Björn; Ramírez, Fidel; Manke, Thomas

doi:10.1093/bioinformatics/btaa692

Cited by 281 publications

(223 citation statements)

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“…The profiles were smoothened using a window size of 11 fragments. The track profiles were obtained using pygenometracks ( 52 ). To quantify the contacts with enhancers, a region of interactions around each of them was defined based on the peak calling (wSize = 11, qWd = 1.5, qWr = 0.6) obtained by peakC ( 53 ) on the wild-type 4C-seq tracks of Hoxd11 (CS39, chr2:75128401–75162753; CS93, chr2:75194928–75211234, and CS65, chr2:75420048–75444960), Hoxd9 (ELCR2, chr2:74925621–74939634), and Hoxd4 (ELCR3, chr2:75081283–75094718).…”

Section: Methodsmentioning

confidence: 99%

“…In order to display the linear distances of the matrices, the virtual Hi-C output text file was converted to a cool file using a custom python script ( https://github.com/lldelisle/scriptsForRodriguezCarballoEtAl2020 ). The track profiles were obtained using pygenometracks ( 52 ). The replicates and viewpoints used for each set of 4Cin are listed in SI Appendix , Table S4 .…”

Section: Methodsmentioning

confidence: 99%

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Chromatin topology and the timing of enhancer function at the HoxD locus

Rodríguez-Carballo

Lopez-Delisle

Willemin

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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The HoxD gene cluster is critical for proper limb formation in tetrapods. In the emerging limb buds, different subgroups of Hoxd genes respond first to a proximal regulatory signal, then to a distal signal that organizes digits. These two regulations are exclusive from one another and emanate from two distinct topologically associating domains (TADs) flanking HoxD, both containing a range of appropriate enhancer sequences. The telomeric TAD (T-DOM) contains several enhancers active in presumptive forearm cells and is divided into two sub-TADs separated by a CTCF-rich boundary, which defines two regulatory submodules. To understand the importance of this particular regulatory topology to control Hoxd gene transcription in time and space, we either deleted or inverted this sub-TAD boundary, eliminated the CTCF binding sites, or inverted the entire T-DOM to exchange the respective positions of the two sub-TADs. The effects of such perturbations on the transcriptional regulation of Hoxd genes illustrate the requirement of this regulatory topology for the precise timing of gene activation. However, the spatial distribution of transcripts was eventually resumed, showing that the presence of enhancer sequences, rather than either their exact topology or a particular chromatin architecture, is the key factor. We also show that the affinity of enhancers to find their natural target genes can overcome the presence of both a strong TAD border and an unfavorable orientation of CTCF sites.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Chromatin topology and the timing of enhancer function at the HoxD locus

Rodríguez-Carballo

Lopez-Delisle

Willemin

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…We retained only results for which the gene closest to the disruption/creation of a TF is a CH driver. Visualization of the genomic context of the mutations represented in Figure S6 was performed using pyGenomeTracks 79 .…”

Section: Methodsmentioning

confidence: 99%

Discovering the drivers of clonal hematopoiesis

Pich

Reyes-Salazar

González-Pérez

et al. 2020

Preprint

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Mutations in genes that confer a selective advantage to hematopoietic stem cells (HSCs) in certain conditions drive clonal hematopoiesis (CH). While some CH drivers have been identified experimentally or through epidemiological studies, the compendium of all genes able to drive CH upon mutations in HSCs is far from complete. We propose that identifying signals of positive selection in blood somatic mutations may be an effective way to identify CH driver genes, similarly as done to identify cancer genes. Using a reverse somatic variant calling approach, we repurposed whole-genome and whole-exome blood/tumor paired samples of more than 12,000 donors from two large cancer genomics cohorts to identify blood somatic mutations. The application of IntOGen, a robust driver discovery pipeline, to blood somatic mutations across both cohorts, and more than 24,000 targeted sequenced samples yielded a list of close to 70 genes with signals of positive selection in CH, available at http://www.intogen.org/ch. This approach recovers all known CH genes, and discovers novel candidates. Generating this compendium is an essential step to understand the molecular mechanisms of CH and to accurately detect individuals with CH to ascertain their risk to develop related diseases.

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“…The TAD-separation score and the domains were obtained using hicFindTADs version 3.5.2 [78][79][80] with --minBoundaryDistance 100000 and either default parameters for the choice of window size or a fixed window size of 120Kb. Plots were obtained using pyGenomeTracks version 3.6 78,81 .…”

Section: Hi-c/ Chip Seq/ Scrna-seq Data Analysis 4c-seq Interaction Pmentioning

confidence: 99%

“…The coverage was then normalized by the number of million tags used in macs2 coverage. Plots were obtained using pyGenomeTracks version 3.6 78,81 . For DFL_E12_H3K27ac, the two replicates were averaged.…”

Section: Gatcggaagagcacacgtctgaactccagtcac -Amentioning

confidence: 99%

HOX13-MEDIATEDDBX2REGULATION IN LIMBS SUGGESTS INTER-TAD SHARING OF ENHANCERS

Beccari

Jaquier

Lopez-Delisle

et al. 2020

Preprint

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BackgroundDuring tetrapod limb development, the HOXA13 and HOXD13 transcription factors are critical for the emergence and organization of the autopod, the most distal aspect where digits will develop. Since previous work had suggested that the Dbx2 gene is a target of these factors, we set up to analyze in detail this potential regulatory interaction.ResultsWe show that HOX13 proteins bind to eutherian-specific sequences at the vicinity of the Dbx2 locus that have enhancer activity in developing digits. However, the functional inactivation of the DBX2 protein did not elicit any particular phenotype related to Hox genes inactivation in digits, suggesting either redundant or compensatory mechanisms. We report that the neighboring Nell2 and Ano6 genes are also expressed in distal limb buds and are, in part, controlled by the same Dbx2 enhancers despite being localized into two different topologically associating domains (TADs) flanking the Dbx2 locus.ConclusionsWe conclude that Hoxa13 and Hoxd genes cooperatively activate Dbx2 expression in developing digits through binding to eutherian specific regulators elements in the Dbx2 neighborhood. Furthermore, these enhancers can overcome TAD boundaries in either direction to co-regulate a set of genes located in distinct chromatin domains.Bullet pointsHoxa13 and Hoxd genes cooperatively regulate Dbx2 expression in developing digits via eutherian specific enhancers.Dbx2 is expressed in different digit joint precursors but its function there is not essential.Dbx2 enhancers also control the expression of the Nell2 and Ano6 genes, which are located in different TADs, thus overcoming the boundary effect.Dbx2 chromatin architecture and enhancers evolved in the mammalian lineage.Grant Sponsor and NumberSwiss National Research Foundation #310030B_138662.European Research Council grants RegulHox #588029

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pyGenomeTracks: reproducible plots for multivariate genomic datasets

Cited by 281 publications

References 10 publications

Chromatin topology and the timing of enhancer function at the HoxD locus

Chromatin topology and the timing of enhancer function at the HoxD locus

Discovering the drivers of clonal hematopoiesis

HOX13-MEDIATEDDBX2REGULATION IN LIMBS SUGGESTS INTER-TAD SHARING OF ENHANCERS

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