An official website of the United States government
Abstract DNA methylation plays an important role in many biological processes. The mechanisms underlying the establishment and maintenance of DNA methylation are well understood thanks to decades of research using DNA methylation mutants, primarily in Arabidopsis (Arabidopsis thaliana) accession Col-0. Recent genome-wide association studies (GWASs) using the methylomes of natural accessions have uncovered a complex and distinct genetic basis of variation in DNA methylation at the population level. Sequencing following bisulfite treatment has served as an excellent method for quantifying DNA methylation. Unlike studies focusing on specific accessions with reference genomes, population-scale methylome research often requires an additional round of sequencing beyond obtaining genome assemblies or genetic variations from whole-genome sequencing data, which can be cost prohibitive. Here, we provide an overview of recently developed bisulfite-free methods for quantifying methylation and cost-effective approaches for the simultaneous detection of genetic and epigenetic information. We also discuss the plasticity of DNA methylation in a specific Arabidopsis accession, the contribution of DNA methylation to plant adaptation, and the genetic determinants of variation in DNA methylation in natural populations. The recently developed technology and knowledge will greatly benefit future studies in population epigenomes.
more »
« less
In-vitro validated methods for encoding digital data in deoxyribonucleic acid (DNA)
Abstract Deoxyribonucleic acid (DNA) is emerging as an alternative archival memory technology. Recent advancements in DNA synthesis and sequencing have both increased the capacity and decreased the cost of storing information in de novo synthesized DNA pools. In this survey, we review methods for translating digital data to and/or from DNA molecules. An emphasis is placed on methods which have been validated by storing and retrieving real-world data via in-vitro experiments.
more »
« less
- PAR ID:
- 10408376
- Publisher / Repository:
- Springer Science + Business Media
- Date Published:
- Journal Name:
- BMC Bioinformatics
- Volume:
- 24
- Issue:
- 1
- ISSN:
- 1471-2105
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
null (Ed.)Deoxyribonucleic Acid (DNA) as a storage medium with high density and long-term preservation properties can satisfy the requirement of archival storage for rapidly increased digital volume. The read and write processes of DNA storage are error-prone. Images widely used in social media have the properties of fault tolerance which are well fitted to the DNA storage. However, prior work simply investigated the feasibility of DNA storage storing different types of data and simply store images in DNA storage, which did not fully investigate the fault-tolerant potential of images in the DNA storage. In this paper, we proposed a new image-based DNA system called IMG-DNA, which can efficiently store images in DNA storage with improved DNA storage robustness. First, a new DNA architecture is proposed to fit JPEG-based images and improve the image’s robustness in DNA storage. Moreover, barriers inserted in DNA sequences efficiently prevent error propagation in images of DNA storage. The experimental results indicate that the proposed IMG-DNA achieves much higher fault-tolerant than prior work.more » « less
-
Abstract Xeno-nucleic acids (XNAs) are synthetic genetic polymers with backbone structures composed of non-ribose or non-deoxyribose sugars. Phosphonomethylthreosyl nucleic acid (pTNA), a type of XNA that does not base pair with DNA or RNA, has been suggested as a possible genetic material for storing synthetic biology information in cells. A critical step in this process is the synthesis of XNA episomes using laboratory-evolved polymerases to copy DNA information into XNA. Here, we investigate the polymerase recognition of pTNA nucleotides using X-ray crystallography to capture the post-catalytic complex of engineered polymerases following the sequential addition of two pTNA nucleotides onto the 3′-end of a DNA primer. High-resolution crystal structures reveal that the polymerase mediates Watson–Crick base pairing between the extended pTNA adducts and the DNA template. Comparative analysis studies demonstrate that the sugar conformation and backbone position of pTNA are structurally more similar to threose nucleic acid than DNA even though pTNA and DNA share the same six-atom backbone repeat length. Collectively, these findings provide new insight into the structural determinants that guide the enzymatic synthesis of an orthogonal genetic polymer, and may lead to the discovery of new variants that function with enhanced activity.more » « less
-
Abstract The CRISPR integrases Cas1-Cas2 create immunological memories of viral infection by storing phage-derived DNA in CRISPR arrays, a process known as CRISPR adaptation. A number of host factors have been shown to influence adaptation, but the full pathway from infection to a fully integrated, phage-derived sequences in the array remains incomplete. Here, we deploy a new CRISPRi-based screen to identify putative host factors that participate in CRISPR adaptation in the Escherichia coli Type I-E system. Our screen and subsequent mechanistic characterization reveal that SspA, through its role as a global transcriptional regulator of cellular stress, is required for functional CRISPR adaptation. One target of SspA is H-NS, a known repressor of CRISPR interference proteins, but we find that the role of SspA on adaptation is not H-NS-dependent. We propose a new model of CRISPR-Cas defense that includes independent cellular control of adaptation and interference by SspA.more » « less
-
Abstract Language Models (LM) have been extensively utilized for learning DNA sequence patterns and generating synthetic sequences. In this paper, we present a novel approach for the generation of synthetic DNA data using pangenomes in combination with LM. We introduce three innovative pangenome-based tokenization schemes, including two that can decouple from private data, while enhance long DNA sequence generation. Our experimental results demonstrate the superiority of pangenome-based tokenization over classical methods in generating high-utility synthetic DNA sequences, highlighting a promising direction for the public sharing of genomic datasets.more » « less
