Landscape of G-quadruplex DNA structural regions in breast cancer

Hänsel‐Hertsch, Robert; Simeone, Angela; Shea, Abigail; Hui, Winnie W I; Zyner, Katherine G.; Marsico, Giovanni; Rueda, Oscar M.; Bruna, Alejandra; Martin, Alistair; Zhang, Xiaoyun; Adhikari, Santosh; Tannahill, David; Caldas, Carlos; Balasubramanian, Shankar

doi:10.1038/s41588-020-0672-8

Cited by 152 publications

(134 citation statements)

References 36 publications

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“…Data were mapped to hg19. We downloaded processed qG4 ChIP-seq (similar to BG4 ChIP-seq) peaks mapped to hg19 for breast cancer [20]. We downloaded processed G4-seq peaks mapped to hg19 from GEO accession number GSE63874 [9].…”

Section: Methodsmentioning

confidence: 99%

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DeepG4 : A deep learning approach to predict active G-quadruplexes from DNA

Rocher

Genais

Nassereddine

et al. 2020

Preprint

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DNA is a complex molecule carrying the instructions an organism needs to develop, live and reproduce. In 1953, Watson and Crick discovered that DNA is composed of two chains forming a double-helix. Later on, other structures of DNA were discovered and shown to play important roles in the cell, in particular G-quadruplex (G4). Following genome sequencing, several bioinformatic algorithms were developed to map G4s in vitro based on a canonical sequence motif, G-richness and G-skewness or alternatively sequence features including k-mers, and more recently deep learning. Here, we propose a novel convolutional neural network (DeepG4) to map active G4s (forming both in vitro and in vivo). DeepG4 is very accurate to predict active G4s, while most state-of-the-art algorithms fail. Moreover, DeepG4 identifies key DNA motifs that are predictive of G4 activity. We found that active G4 motifs do not follow a very flexible sequence pattern as current algorithms seek for. Instead, active G4s are determined by numerous specific motifs. Moreover, among those motifs, we identified known transcription factors which could play important roles in G4 activity by contributing either directly to G4 structures themselves or indirectly by participating in G4 formation in the vicinity. Lastly, variant analysis suggests that SNPs altering predicted G4 activity could affect transcription and chromatin, e.g. gene expression, H3K4me3 mark and DNA methylation. Thus, DeepG4 paves the way for future studies assessing the impact of known disease-associated variants on DNA secondary structure by providing a mechanistic interpretation of SNP impact on transcription and chromatin.

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Section: Methodsmentioning

confidence: 99%

“…Moreover, G4s are also fragile sites and prone to DNA double-strand breaks [30]. Accordingly, G4s are highly suspected to be implicated in human diseases such as cancer or neurological/psychiatric disorders [1,11,20].…”

Section: Introductionmentioning

confidence: 99%

DeepG4 : A deep learning approach to predict active G-quadruplexes from DNA

Rocher

Genais

Nassereddine

et al. 2020

Preprint

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“…In addition, photoexcitation of the complexes gives a low-energy 3 MMLCT emission in the NIR region. Apart from monitoring G-quadruplex formation, which is an important diagnostic to inform diseases such as cancer [24][25][26] and neurological disorders, [27][28][29] the selectivity of complex 1 toward potassium ions has also been examined by adding various cations. The results display negative responses to all other cations, implying the superior potassium ion-targeting specificity.…”

Section: Cationic Alkynylplatinum(ii) Polypyridine Complexes As Biomentioning

confidence: 99%

Recent advances in supramolecular self‐assembly and biological applications of luminescent alkynylplatinum(II) polypyridine complexes

Yam

Law

2020

J Chinese Chemical Soc

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Among various transition metal complexes, platinum(II) complexes are among one of the most extensively explored classes of metal complexes for supramolecular assembly, as their square-planar molecular geometry allows axial interactions between adjacent complex molecules and access to the formation of supramolecular assemblies with the aid of noncovalent Pt(II)Á Á ÁPt(II) interactions. In the presence of external stimuli, alkynylplatinum(II) polypyridine complexes can selfassemble with alterations in their spectroscopic and luminescence properties. In light of their inherent advantages, including low-energy photoexcitation, red to near-infrared emission, large Stokes shifts, long phosphorescence lifetimes and high photostability, successful applications of alkynylplatinum(II) polypyridine complexes in the detection of biological analytes have been made possible. In this account, presented in part of the FACS Foundation Lecture, we introduce the basic concepts and our recent advances in the development of detection assays for various biomolecules based on luminescent alkynylplatinum(II) polypyridine complexes with selected examples.

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“…Therefore, CX-3543, CX-5461 and BMH-21 exhibit potent antitumor activity in cancer models. It has also been shown that endogenous G4 levels can predict sensitivity of tumors to G4 ligands (36).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide mapping of G-quadruplex structures with CUT&Tag

Lyu

Shao

Elsässer

2021

Preprint

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Single-stranded genomic DNA can fold into G-quadruplex (G4) structures or form DNA:RNA hybrids (R loops). Recent evidence suggests that such non-canonical DNA structures affect gene expression, DNA methylation, replication fork progression and genome stability. When and how G4 structures form and are resolved remains unclear. Here we report the use of Cleavage Under Targets and Tagmentation (CUT&Tag) for mapping native G4 in mammalian cell lines at high resolution and low background. Mild native conditions used for the procedure retain more G4 structures and provide a higher signal-to-noise ratio than ChIP-based methods. We determine the G4 landscape of mouse embryonic stem cells (mESC), observing widespread G4 formation at active promoters, active and poised enhancers. We discover that the presence of G4 motifs and G4 structures distinguishes active and primed enhancers in mESCs. Further, performing R-loop CUT&Tag, we demonstrate the genome-wide co-occurence of single-stranded DNA, G4s and R loops, suggesting an intricate relationship between transcription and non-canonical DNA structures.

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Landscape of G-quadruplex DNA structural regions in breast cancer

Cited by 152 publications

References 36 publications

DeepG4 : A deep learning approach to predict active G-quadruplexes from DNA

DeepG4 : A deep learning approach to predict active G-quadruplexes from DNA

Recent advances in supramolecular self‐assembly and biological applications of luminescent alkynylplatinum(II) polypyridine complexes

Genome-wide mapping of G-quadruplex structures with CUT&Tag

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