Database for Modified Nucleotides, Fluorophors and Additives

DMASoftware Inc.的使命是通过编写企业级的模拟程序， 结合核酸热力学和动力学的最新知识的软件 折叠和杂交。为了实现这一目标，DNA软件已经建立了寡核苷酸建模 平台（OMP），准确预测目标二级结构，计算探针杂交 热力学，模拟基于DNA或RNA的测定，自动选择探针和PCR引物，以及 集成了BLAST和CLUSTAL序列比对功能。OMP使用标准化架构， 这允许它接受不同的输入和输出数据结构，并将联合收割机模块组合成可部署的 时尚. OMP已经成功地商业化，并显示出减少了开发时间， 提高涉及寡核苷酸杂交的任何过程的可靠性，例如多重PCR、DNA 测序、SNP检测分析、mRNA表达谱和各种芯片阵列。 该提案的重点是扩大OMP的能力，以设计探针和引物， 修饰的核苷酸、荧光团标记并在缓冲添加剂存在下杂交。这将使 基于核酸的诊断应用，其利用这些修饰来增强灵敏度，特异性， 多重化和改善诊断探针的体内性质。 目前，缺乏针对修饰核苷酸、荧光团的实验热力学参数 和缓冲添加剂损害了OMP在预测杂交和设计有效的修饰 寡核苷酸这项建议将通过提供实验测量的热力学数据来缩小这一差距。 最常用的修饰、荧光团和缓冲添加剂的参数。这些参数将 纳入办公室管理计划并公开提供。

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.