DNA设计：通过突变进行合成DNA的特征感知计算机模拟设计。

DNAdesign: feature-aware in silico design of synthetic DNA through mutation.

作者信息

Wang Yingfei, Li Jinsen, Chiu Tsu-Pei, Gompel Nicolas, Rohs Remo

机构信息

Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, United States.

Department of Evolutionary Biology and Ecology, Bonn Institute for Organismic Biology, University of Bonn, Bonn 53115, Germany.

出版信息

Bioinformatics. 2025 Feb 4;41(2). doi: 10.1093/bioinformatics/btaf052.

DOI:10.1093/bioinformatics/btaf052

PMID:39891349

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11825384/

Abstract

MOTIVATION

DNA sequence and shape readout represent different modes of protein-DNA recognition. Current tools lack the functionality to simultaneously consider alterations in different readout modes caused by sequence mutations. DNAdesign is a web-based tool to compare and design mutations based on both DNA sequence and shape characteristics. Users input a wild-type sequence, select sites to introduce mutations and choose a set of DNA shape parameters for mutation design.

RESULTS

DNAdesign utilizes Deep DNAshape to provide ultra-fast predictions of DNA shape based on extended k-mers and offers multiple encoding methods for nucleotide sequences, including the physicochemical encoding of DNA through their functional groups in the major and minor groove. DNAdesign provides all mutation candidates along the sequence and shape dimensions, with interactive visualization comparing each candidate with the wild-type DNA molecule. DNAdesign provides an approach to studying gene regulation and applications in synthetic biology, such as the design of synthetic enhancers and transcription factor binding sites.

AVAILABILITY AND IMPLEMENTATION

The DNAdesign webserver and documentation are freely accessible at https://dnadesign.usc.edu.

摘要

动机

DNA序列和形状识别代表了蛋白质-DNA识别的不同模式。当前的工具缺乏同时考虑由序列突变引起的不同识别模式变化的功能。DNAdesign是一个基于网络的工具，可根据DNA序列和形状特征比较和设计突变。用户输入野生型序列，选择引入突变的位点，并选择一组用于突变设计的DNA形状参数。

结果

DNAdesign利用Deep DNAshape基于扩展k-mer提供超快速的DNA形状预测，并为核苷酸序列提供多种编码方法，包括通过其在大沟和小沟中的官能团对DNA进行物理化学编码。DNAdesign沿着序列和形状维度提供所有突变候选物，并通过交互式可视化将每个候选物与野生型DNA分子进行比较。DNAdesign提供了一种研究基因调控的方法以及在合成生物学中的应用，例如合成增强子和转录因子结合位点的设计。