For over 60 years, the synthetic production of new DNA sequences has helped researchers understand and engineer biology. Here we summarize methods and caveats for the de novo synthesis of DNA, with particular emphasis on recent technologies that allow for large-scale and low-cost production. In addition, we discuss emerging applications enabled by large-scale de novo DNA constructs, as well as the challenges and opportunities that lie ahead.
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http://dx.doi.org/10.1038/nmeth.2918 | DOI Listing |
Alzheimers Dement (N Y)
January 2025
Indiana Alzheimer Disease Research Center and Center for Neuroimaging, Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana USA.
Introduction: The exponential growth of genomic datasets necessitates advanced analytical tools to effectively identify genetic loci from large-scale high throughput sequencing data. This study presents Deep-Block, a multi-stage deep learning framework that incorporates biological knowledge into its AI architecture to identify genetic regions as significantly associated with Alzheimer's disease (AD). The framework employs a three-stage approach: (1) genome segmentation based on linkage disequilibrium (LD) patterns, (2) selection of relevant LD blocks using sparse attention mechanisms, and (3) application of TabNet and Random Forest algorithms to quantify single nucleotide polymorphism (SNP) feature importance, thereby identifying genetic factors contributing to AD risk.
View Article and Find Full Text PDFGenome Biol
January 2025
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, 2800, Denmark.
Background: Streptomyces is a highly diverse genus known for the production of secondary or specialized metabolites with a wide range of applications in the medical and agricultural industries. Several thousand complete or nearly complete Streptomyces genome sequences are now available, affording the opportunity to deeply investigate the biosynthetic potential within these organisms and to advance natural product discovery initiatives.
Results: We perform pangenome analysis on 2371 Streptomyces genomes, including approximately 1200 complete assemblies.
Int J Mol Sci
December 2024
Bioinformatics and Molecular Design Research Center (BMDRC), Incheon 21983, Republic of Korea.
Understanding drug-target interactions is crucial for identifying novel lead compounds, enhancing efficacy, and reducing toxicity. Phenotype-based approaches, like analyzing drug-induced gene expression changes, have shown effectiveness in drug discovery and precision medicine. However, experimentally determining gene expression for all relevant chemicals is impractical, limiting large-scale gene expression-based screening.
View Article and Find Full Text PDFPlant Biotechnol J
January 2025
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
Transposable elements (TEs) are significant drivers of genome evolution, yet their recent dynamics and impacts within and among species, as well as the roles of host genes and non-coding RNAs in the transposition process, remain elusive. With advancements in large-scale pan-genome sequencing and the development of open data sharing, large-scale comparative genomics studies have become feasible. Here, we performed complete de novo TE annotations and identified active TEs in 310 plant genome assemblies across 119 species and seven crop populations.
View Article and Find Full Text PDFAlzheimers Res Ther
January 2025
Alzheimer Center Amsterdam, Department of Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Background: Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for the treatment of type 2 diabetes and obesity and has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms including neuroinflammatory, vascular, and other AD-related processes.
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