Database for Modified Nucleotides, Fluorophors and Additives

DMASoftware Inc.的使命是通过编写企业级模拟来支持基因组学领域 融合了最先进的核酸热力学和动力学知识的软件 折叠和杂交。为了实现这一目标，DNA软件建立了寡核苷酸模型 准确预测靶二级结构的平台(OMP)计算探针杂交 热力学，模拟基于DNA或RNA的分析，自动选择探针和聚合酶链式反应引物，以及 集成了BLAST和CLUSTAL序列比对功能。OMP使用标准化的架构， 这允许它接受不同的输入和输出数据结构，并将模块组合在可部署的 时尚。OMP已经成功地商业化，并被证明可以减少开发时间和 提高涉及寡核苷酸杂交的任何过程的可靠性，如多重PCR、DNA 测序、SNP检测、信使核糖核酸表达谱，以及各种芯片阵列。 该提案侧重于OMP能力的扩展，以设计包含以下内容的探针和引物 修饰的核苷酸、荧光团标记和在缓冲添加剂存在下的杂交。这将使 基于核酸的诊断应用，利用这些修饰来提高敏感性、特异性 以提高诊断探针的体内性能。 目前，缺乏修饰核苷酸、荧光团的实验热力学参数 而缓冲添加剂影响了OMP在预测杂交和设计有效修饰方面的准确性 寡核苷酸。这项提议将通过提供实验测量的热力学来弥合这一差距 最常用的改性剂、荧光团和缓冲剂的参数。这些参数将 被合并到OMP中并公开提供。

The mission of DMASoftware Inc. is to enable the field of genomics by writing enterprise grade simulation software that incorporates state-of-the-art knowledge of the thermodynamics and kinetics of nucleic acid folding and hybridization. To accomplish this goal, DNA Software has built the Oligonucleotide Modeling Platform (OMP), which accurately predicts target secondary structure, calculates probe hybridization thermodynamics, simulates DNA or RNA based assays, automatically selects probes and PCR primers, and integrates BLAST and CLUSTAL sequence alignment capabilities. OMP uses a standardized architecture, which allows it to accept deferent input and output data structures and to combine modules in a deployable fashion. OMP has been successfully commercialized and shown to reduce the development time and improve the reliability of any process involving Oligonucleotide hybridization such as multiplex PCR, DNA sequencing, SNP detection assays, mRNA expression profiling, and a variety of chip arrays. This proposal focuses on the expansion of OMP capability to design probes and primers that contain modified nucleotides, fluorophore labels and hybridize in the presence of buffer additives. This will enable nucleic acid based diagnostic applications that utilize these modifications to enhance sensitivity, specificity, multiplexing and to improve in vivo properties of diagnostic probes. At present, the lack of experimental thermodynamic parameters for modified nucleotides, fluorophores and buffer additives impairs OMP accuracy in predicting hybridization and designing efficient modified oligonucleotides. This proposal will close this gap by providing experimentally measured thermodynamic parameters for most commonly used modifications, fluorophores and buffer additives. These parameters will be incorporated into OMP as well as made publicly available.