Deep learning approach for predicting functional Z-DNA regions using omics data

Beknazarov, Nazar; Jin, Seungmin; Poptsova, Maria

doi:10.1038/s41598-020-76203-1

Cited by 38 publications

(52 citation statements)

References 67 publications

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“…Maria Poptsova [ 10 ] presented computational approaches based on the DeepZ machine learning algorithms to study factors that alter the B to Z flip energetics in vivo and to describe the pathways involved. Structural studies on Z-RNA formation by Quentin Vicens [ 23 ] and Beat Vögeli [ 9 ] outlined some of the different requirements for Z-RNA formation compared to Z-DNA formation, pointing at a widespread distribution of Z-RNA across transcriptomes.…”

Section: Meeting Summarymentioning

confidence: 99%

“…These advances were informed by biochemical, biophysical and structural approaches that established the conditions and base modifications necessary to flip from the right-to left-handed conformation under physiological conditions [9]. Computational analyses established that the localization of the repeats that form Z-DNA is not random [10], consistent with its selection for or against particular outcomes. This inaugural ABZ meeting (https://abz2021.bio, accessed 16 July 2021) was convened to bring together the leading researchers within the different disciplines that study the Z-conformation, with an intent to celebrate and collaborate.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Special Issue: A, B and Z: The Structure, Function and Genetics of Z-DNA and Z-RNA

Herbert

Karapetyan

Poptsova

et al. 2021

IJMS

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It is now difficult to believe that a biological function for the left-handed Z-DNA and Z-RNA conformations was once controversial. The papers in this Special Issue, “Z-DNA and Z-RNA: from Physical Structure to Biological Function”, are based on presentations at the ABZ2021 meeting that was held virtually on 19 May 2021 and provide evidence for several biological functions of these structures. The first of its kind, this international conference gathered over 200 scientists from many disciplines to specifically address progress in research involving Z-DNA and Z-RNA. These high-energy left-handed conformers of B-DNA and A-RNA are associated with biological functions and disease outcomes, as evidenced from both mouse and human genetic studies. These alternative structures, referred to as “flipons”, form under physiological conditions, regulate type I interferon responses and induce necroptosis during viral infection. They can also stimulate genetic instability, resulting in adaptive evolution and diseases such as cancer. The meeting featured cutting-edge science that was, for the most part, unpublished. We plan for the ABZ meeting to reconvene in 2022.

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Section: Meeting Summarymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Special Issue: A, B and Z: The Structure, Function and Genetics of Z-DNA and Z-RNA

Herbert

Karapetyan

Poptsova

et al. 2021

IJMS

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“…Many biochemical and biophysical in vitro experiments have been conducted to better characterise Z-DNA behaviour at close to physiological conditions [ 27 , 28 ] and also to better understand switching between B and Z-DNA [ 29 , 30 ]. Furthermore, several bioinformatic searches have been performed to predict Z-DNA-prone sequence motifs in the genomic DNA of some model organisms, including humans [ 31 , 32 ]. Z-DNA structures can be formed only in specific double-stranded sequences with alternating purine–pyrimidine tracks, which has been determined by crystallography in various nucleotide repeats, where specifically Z-DNA containing GC repeats have been shown to have increased stability [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Searching for New Z-DNA/Z-RNA Binding Proteins Based on Structural Similarity to Experimentally Validated Zα Domain

Bartas

Slychko

Brázda

et al. 2022

IJMS

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Z-DNA and Z-RNA are functionally important left-handed structures of nucleic acids, which play a significant role in several molecular and biological processes including DNA replication, gene expression regulation and viral nucleic acid sensing. Most proteins that have been proven to interact with Z-DNA/Z-RNA contain the so-called Zα domain, which is structurally well conserved. To date, only eight proteins with Zα domain have been described within a few organisms (including human, mouse, Danio rerio, Trypanosoma brucei and some viruses). Therefore, this paper aimed to search for new Z-DNA/Z-RNA binding proteins in the complete PDB structures database and from the AlphaFold2 protein models. A structure-based similarity search found 14 proteins with highly similar Zα domain structure in experimentally-defined proteins and 185 proteins with a putative Zα domain using the AlphaFold2 models. Structure-based alignment and molecular docking confirmed high functional conservation of amino acids involved in Z-DNA/Z-RNA, suggesting that Z-DNA/Z-RNA recognition may play an important role in a variety of cellular processes.

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“…Whereas poly(deoxyguanylic-deoxycytidylic) acid [poly(dG-dC).poly(dG-dC)], further abbreviated in this paper to [poly(dG-dC)], can undergo a B-to Z-DNA transition at highsalt conditions, bromination of poly(dG-dC) [Br-poly(dG-dC)] produces a synthetic DNA in which the Z-DNA conformation is present at low-salt conditions [3]. Algorithms to predict the presence of Z-DNA on the basis of thermodynamic considerations indicate that a variety of sequences, and not just alternating pyrimidine-purine tracts, can form Z-DNA in the genome [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

The Binding of Monoclonal and Polyclonal Anti-Z-DNA Antibodies to DNA of Various Species Origin

Spencer

Reyna

Pisetsky

2021

IJMS

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DNA is a polymeric macromolecule that can display a variety of backbone conformations. While the classical B-DNA is a right-handed double helix, Z-DNA is a left-handed helix with a zig-zag orientation. The Z conformation depends upon the base sequence, base modification and supercoiling and is considered to be transient. To determine whether the presence of Z-DNA can be detected immunochemically, the binding of monoclonal and polyclonal anti-Z-DNA antibodies to a panel of natural DNA antigens was assessed by an ELISA using brominated poly(dG-dC) as a control for Z-DNA. As these studies showed, among natural DNA tested (Micrococcus luteus, calf thymus, Escherichiacoli, salmon sperm, lambda phage), micrococcal (MC) DNA showed the highest binding with both anti-Z-DNA preparations, and E. coli DNA showed binding with the monoclonal anti-DNA preparation. The specificity for Z-DNA conformation in MC DNA was demonstrated by an inhibition binding assay. An algorithm to identify propensity to form Z-DNA indicated that DNA from Mycobacterium tuberculosis could form Z-DNA, a prediction confirmed by immunoassay. Together, these findings indicate that anti-Z-DNA antibodies can serve as probes for the presence of Z-DNA in DNA of various species origin and that the content of Z-DNA varies significantly among DNA sources.

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Deep learning approach for predicting functional Z-DNA regions using omics data

Cited by 38 publications

References 67 publications

Special Issue: A, B and Z: The Structure, Function and Genetics of Z-DNA and Z-RNA

Special Issue: A, B and Z: The Structure, Function and Genetics of Z-DNA and Z-RNA

Searching for New Z-DNA/Z-RNA Binding Proteins Based on Structural Similarity to Experimentally Validated Zα Domain

The Binding of Monoclonal and Polyclonal Anti-Z-DNA Antibodies to DNA of Various Species Origin

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