<i>TreeAndLeaf</i>: an R/Bioconductor package for graphs and trees with focus on the leaves

Cardoso, Milena A.; Rizzardi, Luis E A; Kume, Leonardo W; Groeneveld, Clarice S.; Trefflich, Sheyla; Morais, Diego Arthur de Azevedo; Dalmolin, Rodrigo Juliani Siqueira; Ponder, Bruce A.J.; Meyer, Kerstin B.; Castro, Mauro A. A.

doi:10.1093/bioinformatics/btab819

Cited by 6 publications

(4 citation statements)

References 6 publications

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“…The heatmaps were plotted using the R package pheatmap (version 1.0.12), while the circos plots were generated with the R package circlize (version 0.4.15) [ 32 ]. We also performed clustering analysis to identify relationships across all 57 cohorts with known episignatures and generated a tree and leaf plot using the R package TreeAndLeaf (version 1.6.1) [ 33 ] to visualize the distance and similarities between the cohorts. Additionally, we used the R package annotatr (version 1.20.0) [ 34 ] with AnnotationHub (version 3.2.2) as previously described by Levy et al [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of the DNA methylation signature of Mowat-Wilson syndrome

Caraffi,

van der Laan,

Rooney

et al. 2024

Eur J Hum Genet

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Mowat-Wilson syndrome (MOWS) is a rare congenital disease caused by haploinsufficiency of ZEB2, encoding a transcription factor required for neurodevelopment. MOWS is characterized by intellectual disability, epilepsy, typical facial phenotype and other anomalies, such as short stature, Hirschsprung disease, brain and heart defects. Despite some recognizable features, MOWS rarity and phenotypic variability may complicate its diagnosis, particularly in the neonatal period. In order to define a novel diagnostic biomarker for MOWS, we determined the genome-wide DNA methylation profile of DNA samples from 29 individuals with confirmed clinical and molecular diagnosis. Through multidimensional scaling and hierarchical clustering analysis, we identified and validated a DNA methylation signature involving 296 differentially methylated probes as part of the broader MOWS DNA methylation profile. The prevalence of hypomethylated CpG sites agrees with the main role of ZEB2 as a transcriptional repressor, while differential methylation within the ZEB2 locus supports the previously proposed autoregulation ability. Correlation studies compared the MOWS cohort with 56 previously described DNA methylation profiles of other neurodevelopmental disorders, further validating the specificity of this biomarker. In conclusion, MOWS DNA methylation signature is highly sensitive and reproducible, providing a useful tool to facilitate diagnosis.

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Section: Methodsmentioning

confidence: 99%

Identification of the DNA methylation signature of Mowat-Wilson syndrome

Caraffi,

van der Laan,

Rooney

et al. 2024

Eur J Hum Genet

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“…Then, modules correlated with the two KD contexts were considered for network visualization. Graphical network visualization was performed using the RedeR v2.4.3 and the TreeAndLeaf v1.12.0 packages from the R platform [ 57 , 58 ].…”

Section: Methodsmentioning

confidence: 99%

Deciphering “Immaturity-Stemness” in Human Epidermal Stem Cells at the Levels of Protein-Coding and Non-Coding Genomes: A Prospective Computational Approach

Vinasco-Sandoval,

Lemaître,

Soularue

et al. 2024

IJMS

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The epidermis hosts populations of epithelial stem cells endowed with well-documented renewal and regenerative functions. This tissue thus constitutes a model for exploring the molecular characteristics of stem cells, which remain to date partially characterized at the molecular level in human skin. Our group has investigated the regulatory functions of the KLF4/TGFB1 and the MAD4/MAX/MYC signaling pathways in the control of the immaturity-stemness versus differentiation fate of keratinocyte stem and precursor cells from human interfollicular epidermis. We described that down-modulation of either KLF4 or MXD4/MAD4 using RNA interference tools promoted an augmented stemness cellular status; an effect which was associated with significant transcriptional changes, as assessed by RNA-sequencing. Here, we have implemented a computational approach aimed at integrating the level of the coding genome, comprising the transcripts encoding conventional proteins, and the non-coding genome, with a focus on long non-coding RNAs (lncRNAs). In addition, datasets of micro-RNAs (miRNAs) with validated functions were interrogated in view of identifying miRNAs that could make the link between protein-coding and non-coding transcripts. Putative regulons comprising both coding and long non-coding transcripts were built, which are expected to contain original pro-stemness candidate effectors available for functional validation approaches. In summary, interpretation of our basic functional data together with in silico biomodeling gave rise to a prospective picture of the complex constellation of transcripts regulating the keratinocyte stemness status.

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“…We performed functional annotation analyses to compare our BIS-HVDAS episignature with the other 56 EpiSign™ disorders based on previously published articles (Levy, Relator, et al, TreeAndLeaf (version 1.6.1) (Cardoso et al, 2022). Finally, we annotated all probes in relation to CpG island (CGIs) and genes with annotatr (version 1.20.0) (Cavalcante & Sartor, 2017) with Annota-tionHub (version 3.2.2) to discover the genomic location of the selected DMPs as described previously by Levy, Relator, et al (2022).…”

Section: Overlap Of the Bis-hvdas Genome-wide Dna Methylation Profile...mentioning

confidence: 99%

Blepharophimosis with intellectual disability and Helsmoortel‐Van Der Aa Syndrome share episignature and phenotype

Sarli,

van der Laan,

Reilly

et al. 2024

American J of Med Genetics Pt C

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Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides‐Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in SMARCA2, that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM‐associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of ADNP present with the neurodevelopmental disorder known as Helsmoortel‐Van Der Aa Syndrome (HVDAS). Distinct DNA methylation profiles referred to as episignatures have been reported in HVDAS and BAF complex disorders. Due to molecular interactions between ADNP and BAF complex, and an overlapping craniofacial phenotype with narrowing of the palpebral fissures in a subset of patients with HVDAS and BIS, we hypothesized the possibility of a common phenotype‐specific episignature. A distinct episignature was shared by 15 individuals with BIS‐causing SMARCA2 pathogenic variants and 12 individuals with class II HVDAS caused by truncating pathogenic ADNP variants. This represents first evidence of a sensitive phenotype‐specific episignature biomarker shared across distinct genetic conditions that also exhibit unique gene‐specific episignatures.

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TreeAndLeaf: an R/Bioconductor package for graphs and trees with focus on the leaves

Cited by 6 publications

References 6 publications

Identification of the DNA methylation signature of Mowat-Wilson syndrome

Identification of the DNA methylation signature of Mowat-Wilson syndrome

Deciphering “Immaturity-Stemness” in Human Epidermal Stem Cells at the Levels of Protein-Coding and Non-Coding Genomes: A Prospective Computational Approach

Blepharophimosis with intellectual disability and Helsmoortel‐Van Der Aa Syndrome share episignature and phenotype

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