DNA methylation has been associated with transcriptional repression and detection of differential is important in understanding the underlying causes gene expression. Bisulfite-converted genomic sequencing current gold standard field for building genome-wide maps at a base pair resolution methylation. Here we systematically investigate features detecting CpG non-CpG contexts, considering both case mammalian systems plants. In particular, introduce DMRcaller, highly efficient R/Bioconductor...

Sex differences are known to play a role in disease aetiology, progression and outcome. Previous studies have revealed autosomal epigenetic between males females some tissues, including DNA methylation patterns. Here, we report for the first time an analysis of sex DNAme using Illumina EPIC array human whole blood by performing discovery (n = 1171) validation 2471) analysis.We identified validated 396 sex-associated differentially methylated CpG sites (saDMPs) with majority found be...

Abstract Mammalian genomes harbor abundant transposable elements (TEs) and their remnants, with numerous epigenetic repression mechanisms enacted to silence TE transcription. However, TEs are upregulated during early development, neuronal lineage, cancers, although the factors contributing transcription of have yet be fully elucidated. Here, we demonstrate that male-specific lethal (MSL)-complex-mediated histone H4 acetylation at lysine 16 (H4K16ac) is enriched in human embryonic stem cells...

Abstract Artificial intelligence (AI) is revolutionizing many real-world applications in various domains. In the field of genomics, multiple traditional machine-learning approaches have been used to understand dynamics genetic data. These provided acceptable predictions; however, these are based on opaque-box AI algorithms which not able provide needed transparency community. Recently, explainable artificial has emerged overcome interpretation problem opaque box models by aiming complete...

The DNA in many organisms, including humans, is shown to be organized topologically associating domains (TADs). In Drosophila , several architectural proteins are enriched at TAD borders, but it still unclear whether these play a functional role the formation and maintenance of TADs. Here, we show that depletion BEAF-32, Cp190, Chro, Dref leads changes organization chromatin loops. Their predominantly affects borders located regions moderately repressive modifications depleted active ones,...

Transcription factors (TFs) are proteins that affect gene expression by binding to regulatory regions of DNA in a sequence specific manner. The TFs is controlled many factors, including the sequence, concentration TF, chromatin accessibility and co-factors. Here, we systematically investigated mechanism hundreds analysing ChIP-seq data with our explainable statistical model, ChIPanalyser. This tool uses as inputs motif; capacity distinguish between strong weak sites; TF; accessibility. We...

Transgenerationally heritable epialleles are defined by the stable propagation of alternative transcriptional states through mitotic and meiotic cell cycles. Given that DNA methylation at CpG sites, mediated in Arabidopsis MET1, plays a central role epigenetic inheritance, we examined genomewide partial complete loss-of-function met1 mutants. We interpreted data relation to transgenerational epiallelic stability, which allowed us classify chromosomal targets regulation into (i) single copy...

The organization of the genome into topologically associating domains (TADs) was shown to have a regulatory role in development and cellular function, but mechanism involved TAD establishment is still unclear. Here, we present first high-resolution contact map Drosophila neuronal cells (BG3) identify different classes TADs by comparing this embryonic (Kc167). We find that only some are conserved both cell lines, whereas rest cell-type–specific. This supported change enrichment architectural...

Abstract Background Glioblastoma is the most common and aggressive malignant brain tumour in adult population its prognosis dismal. The heterogeneous nature of tumour, to which epigenetic dysregulation significantly contributes, among main therapeutic challenges disease. Results We have leveraged SYNGN, an experimental pipeline enabling syngeneic comparison glioblastoma stem cells expanded potential cell (EPSC)-derived neural identify regulatory features driven by chromatin remodelling...

Retrotransposons containing long terminal repeats (LTRs) form a substantial fraction of eukaryotic genomes. The timing past transposition can be estimated by quantifying the accumulation mutations in initially identical LTRs. This way, retrotransposons are divided into young, potentially mobile elements, and old that moved thousands or even millions years ago. Both types found within single retrotransposon family it is assumed members will remain immobile degenerate further. Here, we provide...

The binding of transcription factors (TFs) is essential for gene expression. One important characteristic the actual occupancy a putative site in genome. In this study, we propose an analytical model to predict genomic that incorporates preferred target sequence TF form position weight matrix (PWM), DNA accessibility data (in case eukaryotes), number molecules expected be bound specifically and parameter modulates specificity TF. Given ChIP-seq profiles, backwards inferred copy five...

Methylation of cytosine is an epigenetic mark involved in the regulation transcription, usually associated with transcriptional repression. In mammals, methylated cytosines are found predominantly CpGs but plants non-CpG methylation (in CpHpG or CpHpH contexts, where H A, C T) also present and silencing transposable elements. addition, CpG coding regions active genes. absence demethylase lysine 9 histone 3 (IBM1), a subset body-methylated genes acquires methylation. This was shown to alter...

Abstract Background Enhancers are non-coding regions of the genome that control activity target genes. Recent efforts to identify active enhancers experimentally and in silico have proven effective. While these tools can predict locations with a high degree accuracy, mechanisms underpinning often unclear. Results Using machine learning (ML) rule-based explainable artificial intelligence (XAI) model, we demonstrate location known Drosophila accuracy. Most importantly, use rules XAI model...

Abstract Background Epigenetic changes play a key role in the pathogenesis of medulloblastoma (MB), most common malignant pediatric brain tumor. Methods We explore therapeutic potential BMI1 and MAPK/ERK inhibition BMI1High;CHD7Low MB cells preclinical xenograft model. Results identify synergistic vulnerability to combination treatment with inhibitors. Mechanistically, CHD7-dependent binding MAPK-regulated genes underpins CHD7-BMI1-MAPK regulatory axis responsible antitumour effect...

Site-specific transcription factors (TFs) bind to their target sites on the DNA, where they regulate rate at which genes are transcribed. Bacterial TFs undergo facilitated diffusion (a combination of 3D around and 1D random walk DNA) when searching for sites. Using computer simulations this search process, we show that organisation binding sites, in conjunction with TF copy number site affinity, plays an important role determining not only steady state promoter occupancy, but also order...

Abstract Interindividual genetic variability is well characterised, but we still lack a complete catalogue of loci displaying variable and stable epigenetic patterns. Here, report interindividual DNA methylation in human whole blood by analysing the patterns 3642 individuals using IlluminaEPIC array. Our results showed that 41,216 CpGs display (SMPs) 34,972 levels (VMPs). This will be useful resource for interpretation when associating signals to phenotypes. We observed SMPs are highly...

Much is now known about the mechanistic details of gene translation. There are also rapid advances in high-throughput technologies to determine quantitative aspects system. As a consequence-realistic and system-wide simulation models translation feasible. Such needed as devices integrate large volume highly fragmented data Software: In this application note, we present novel, efficient software tool model The represents main Features include representation exhaustible tRNA pools,...

Transcription factor (TF) molecules translocate by facilitated diffusion (a combination of 3D around and 1D random walk on the DNA). Despite attention this mechanism received in last 40 years, only a few studies investigated influence cellular environment and, particular, `other' DNA binding proteins competing with TF for space. Molecular crowding is likely to association rate TFs their target site steady state occupancy those sites, but it still not clear how influences search genome-wide...

We analyse the trade-off between speed with which a gene can propagate information, noise of its output and metabolic cost. Our main finding is that for any given level cost there an optimal processing speed. Any system non-vanishing leak expression rate suboptimal, i.e. it will exhibit higher and/or slower than leak-free systems same also show Hill coefficient h minimizes at fixed speeds, threshold K noise.

Abstract Motivation: Gene activity is mediated by site-specific transcription factors (TFs). Their binding to defined regions in the genome determines rate at which their target genes are transcribed. Results: We present a comprehensive computational model of search process TF for genomic site(s). The considers: DNA sequence, various species and interaction individual molecules with or between themselves. also demonstrate systematic approach how parametrize system using available...