Machine learning model for sequence-driven DNA G-quadruplex formation

Sahakyan, Aleksandr B.; Chambers, Vicki S.; Marsico, Giovanni; Santner, Tobias; Antonio, Marco Di; Balasubramanian, Shankar

doi:10.1038/s41598-017-14017-4

Cited by 132 publications

(141 citation statements)

References 37 publications

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“…The motifs were found to be enriched in regulatory regions, especially promoters, first introns, and telomeres . Subsequent studies have led to the broadening of the G4‐motif definition and to the ongoing refinement of G4‐mining algorithms . However, major G4‐prone genomic fragments, including telomeres and oncogene promoters, are well established and the bioinformatics predictions are generally consistent with those from the G4‐sequencing data .…”

Section: Introductionmentioning

confidence: 94%

DNA G‐Quadruplexes (G4s) Modulate Epigenetic (Re)Programming and Chromatin Remodeling

2019

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Here, the emerging data on DNA G‐quadruplexes (G4s) as epigenetic modulators are reviewed and integrated. This concept has appeared and evolved substantially in recent years. First, persistent G4s (e.g., those stabilized by exogenous ligands) were linked to the loss of the histone code. More recently, transient G4s (i.e., those formed upon replication or transcription and unfolded rapidly by helicases) were implicated in CpG island methylation maintenance and de novo CpG methylation control. The most recent data indicate that there are direct interactions between G4s and chromatin remodeling factors. Finally, multiple findings support the indirect participation of G4s in chromatin reshaping via interactions with remodeling‐related transcription factors (TFs) or damage responders. Here, the links between the above processes are analyzed; also, how further elucidation of these processes may stimulate the progress of epigenetic therapy is discussed, and the remaining open questions are highlighted.

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Section: Introductionmentioning

confidence: 94%

DNA G‐Quadruplexes (G4s) Modulate Epigenetic (Re)Programming and Chromatin Remodeling

2019

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“…Thus, whole‐genome sequencing experiments and bioinformatics studies predict the formation of numerous G4 structures in the genome . However, in spite of some attempts, the stability and folding topology of G4‐DNA and G4‐RNA are difficult to predict purely on the basis of sequence information . A growing body of structural and biophysical data demonstrates that these structures frequently escape the consensus motif (i.e., G n ‐N i ‐G n ‐N j ‐G n ‐N k ‐G n , in which n= 2 to 4; i , j , k =1 to 7; and N=any base), as evidenced by snap‐back, G‐vacant, and bulged G4 structures which are difficult to predict by bioinformatics algorithms .…”

Section: Introductionmentioning

confidence: 99%

Topology‐Selective, Fluorescent “Light‐Up” Probes for G‐Quadruplex DNA Based on Photoinduced Electron Transfer

Xie

Reznichenko

Chaput

et al. 2018

Chemistry A European J

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Six novel probes were prepared by covalent attachment of a G4-DNA ligand (bis(quinolinium) pyridodicarboxamide; PDC) to various coumarin or pyrene fluorophores. In the absence of DNA, the fluorescence of all probes is quenched due to intramolecular photoinduced electron transfer (PET), as evidenced by photophysical and electrochemical studies, molecular modeling, and DFT calculations. All probes demonstrate similarly high thermal stabilization of various G4-DNA substrates belonging to different folding topologies, as assessed by fluorescence melting experiments; however, their fluorimetric response is strongly heterogeneous with respect to the structures of the probes and G4-DNA targets. Thus, the probes containing the 7-diethylaminocoumarin fluorophore demonstrate significant fluorescence enhancement in the presence of G4-DNA, with the strongest "light-up" response (20- to 180-fold) observed for antiparallel G4 structures as well as for hybrid G4 structures, formed by the variants of human telomeric sequence and capable of a conformation change to the antiparallel isoform. These results shed light on the influence of the linker and electronic properties of fluorophores on the efficiency of G4-DNA "light-up" probes operating via PET.

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“…Conversely, we expected G4 motifs to be more abundant in long read assemblies, since these have 353 been suggested to be virtually free from sequence-based biases (Eid et al 2009). To test this, we 354 predicted the presence of G4 motifs using Quadron (Sahakyan et al 2017) in all the different 355 assemblies. All the de-novo Illumina-based assemblies had fewer predicted G4 sites the PacBio 356 assemblies (Figure 3c and Supplementary Table S8).…”

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confidence: 99%

“…The final repeat library also contains the manually curated version of the consensus sequences 969 previously generated on other two birds-of-paradise Astrapia rothschildi "astRot", Ptiloris overlapping hits with a score greater than 19 were used for subsequent analysis as suggested in 978 (Sahakyan et al 2017). The density of such motifs per chromosome model was calculated using 979 bedtools coverage (BEDTools 2.27.1; Quinlan (2014)).…”

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confidence: 99%

Identifying the causes and consequences of assembly gaps using a multiplatform genome assembly of a bird-of-paradise

Peona

Blom

et al. 2019

Preprint

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University 28 29 Correspondence 30 31 V.P. (valentina.peona@ebc.uu.se), A.S. (alexander.suh@ebc.uu.se) 32 33 Abstract 38 39 Genome assemblies are currently being produced at an impressive rate by consortia and individual 40 laboratories. The low costs and increasing efficiency of sequencing technologies have opened up a 41 whole new world of genomic biodiversity. Although these technologies generate high-quality genome 42assemblies, there are still genomic regions difficult to assemble, like repetitive elements and GC-rich 43 regions (genomic "dark matter"). In this study, we compare the efficiency of currently used 44 a non-model organism (paradise crow) for which only suboptimal samples are available. Our 51 approach was able to reconstruct complex chromosomes like the repeat-rich W sex chromosome and 52 several GC-rich microchromosomes. Telomere-to-telomere assemblies are not a reality yet for most 53 organisms, but by leveraging technology choice it is possible to minimize genome assembly gaps for 54 downstream analysis. We provide a roadmap to tailor sequencing projects around the completeness 55 of both the coding and non-coding parts of the genomes. 56 57 2005). It is key now for the genomics field to overcome these limitations and investigate this dark 70 matter. 71 72Repetitive elements represent an important and prevalent part of the genomic dark matter of many 73 genomes, given that their abundance and repetitive nature makes it difficult to fully and confidently 74 assemble their sequences. This is particularly problematic when the read length is significantly shorter 75 than the repetitive element, in which case it is impossible to anchor the reads to unique genomic 76 regions. To what extent repeats can hamper genome assemblies depends on whether they are 77 interspersed or arranged in tandem. Highly similar interspersed repeats, like for example transposable 78

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Machine learning model for sequence-driven DNA G-quadruplex formation

Cited by 132 publications

References 37 publications

DNA G‐Quadruplexes (G4s) Modulate Epigenetic (Re)Programming and Chromatin Remodeling

DNA G‐Quadruplexes (G4s) Modulate Epigenetic (Re)Programming and Chromatin Remodeling

Topology‐Selective, Fluorescent “Light‐Up” Probes for G‐Quadruplex DNA Based on Photoinduced Electron Transfer

Identifying the causes and consequences of assembly gaps using a multiplatform genome assembly of a bird-of-paradise

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