FoxWare™, An Advanced Data Analysis Package for Hydroxyl Radical Foot-Printing Higher Order Structural Analysis

FoxWare™，一种用于羟基自由基足迹高阶结构分析的高级数据分析包

• 批准号: 9907677
• 负责人: Scot Randy Weinberger
• 金额: $ 47.72万
• 依托单位: GENNEXT TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907677
• 关键词: 3-Dimensional; Address; Adopted; Adoption; Adverse Drug Experience Report; Antibody Binding Sites; Appearance; Area; Automation; Award; Binding; Binding Sites; Biological Products; Biological Response Modifier Therapy; Cessation of life; Chemicals; Client; Comparative Study; Complex; Computer software; Consequentialism; Critiques; Dangerousness; Data; Data Analyses; Development; Docking; Drug Targeting; Environment; Epitopes; Evaluation; Goals; Government; Guidelines; Higher Order Chromatin Structure; Home environment; Hydroxyl Radical; Immune response; Industry; Label; Laboratories; Lasers; Letters; Ligands; Link; Location; Manuals; Methods; Modeling; Morbidity - disease rate; Morphologic artifacts; Nature; Patients; Peptides; Pharmaceutical Preparations; Pharmacology; Phase; Play; Process; Production; Protein Analysis; Protein Footprinting; Proteins; Proteomics; Reaction; Research; Research Personnel; Resolution; Role; Safety; Sampling; Scientist; Small Business Innovation Research Grant; Structural defect; Structure; Techniques; Technology; Translating; Ultraviolet Rays; Visualization; Visualization software; Work; adverse drug reaction; analytical tool; biomaterial compatibility; combat; computerized data processing; experimental study; improved; infliximab; interest; irritation; new technology; oxidation; processing speed; programs; protein protein interaction; protein structure; prototype; research and development; software development; tool

The GenNext Phase II SBIR submssion entitled “FoxWare™, an Advanced Data Analysis Package for Hydroxyl Radical Foot-printing Higher Order Structural Analysis” is responsive to the ackowledged need for new and improved tools for higher order structural analysis (HOS) of biopharmaceuticals. Biopharmaceuticals are complex, heterogeneous mixtures of 3-dimensional biomolecules, whose safety and efficacy is reliant upon proper HOS. The presence of proteins with improper HOS has been linked to severe adverse drug reactions (ADR), establishing the need for new and improved HOS analytics. An emerging HOS analysis technique is hydroxyl radical foot-printing (HRPF). HRPF involves the irreversible labeling of a protein's exterior by reaction with hydroxyl radicals with subsequent MS analysis to identify the outer portions of the protein. The most widely used method for generating OH radicals employs a quick burst of UV light, and is appropriately called fast photochemical oxidation of proteins (FPOP). Academic laboratories have demonstrated the utility of FPOP for HOS analysis; however adoption in pharma has been minuscule at best. Guided by the critiques of scientists at leading biopharmaceutical companies, we have identified barriers that have limited pharma's adoption of FPOP HRPF. A substantial barrier is the absence of data processing tools to facilitate HRPF analysis. Today there are no commercial solutions for FPOP analysis, despite the demonstrated market need for its HOS analytical power. Today's proteomics data analysis products fail to adequately address specific work-flow, chemical labeling / artifacts, and comparative study requirements of HRPF HOS analysis. Researchers are compelled to use a piece-meal approach, arduously stitching together results from multiple packages and manually manipulating data in home-brew spreadsheets. As such, data processing represents a significant bottleneck that greatly complicates and delays progress in HRPF HOS studies. Our FoxWare™ software addresses data processing demands of HRPF HOS analysis. Our proposal vastly improves HRPF data analysis by replacing laborious and agonizing present-day practices with an integrated, seamless solution to interpret and amplify the value of HRPF HOS studies. Upon completion of our envisioned program, FoxWare will make an indelible mark upon HOS analysis and impart a transformative shift in analytics and HRPF throughput, addressing the market demands of the biopharmaceutical industry.

名为《FoxWare™，一个高级数据》的GenNext第二阶段SBIR报告 羟基自由基足迹高阶结构分析程序包“is 满足对更高订单的新工具和改进工具的已知需求 生物制药的结构分析(HOS)生物制药是复杂的， 三维生物分子的非均相混合物，其安全性和有效性是 依赖适当的居屋计划。与HOS不正确的蛋白质的存在有关 对严重的药物不良反应(ADR)，建立新的和改进的必要性 Hos Analytics。 一种新兴的HOS分析技术是羟基自由基足迹法(HRPF)。 HRPF涉及通过与羟基反应对蛋白质外部进行不可逆标记 自由基与随后的MS分析以确定蛋白质的外部部分。这个 最广泛使用的产生OH自由基的方法使用快速爆发的紫外光， 并被恰当地称为蛋白质的快速光化学氧化(FPOP)。学术性 实验室已经证明了FPOP用于居屋分析的实用性；但采用 在制药行业，充其量也就是微不足道。在领导的科学家们的批评下 生物制药公司，我们已经确定了限制制药公司 采用FPOP HRPF。一个很大的障碍是缺乏数据处理 促进HRPF分析的工具。目前还没有针对FPOP的商业解决方案 分析，尽管市场对其居屋分析能力有明显的需求。 今天的蛋白质组学数据分析产品不能充分解决特定的 HRPF的工作流程、化学标记/人工制品和比较研究要求 HOS分析。研究人员被迫使用零碎的方法，艰难地 将来自多个包的结果缝合在一起，并在 自制电子表格。因此，数据处理是一个重大的瓶颈 这极大地复杂化和拖延了HRPF居屋研究的进展。我们的Foxware™ 软件解决了HRPF HOS分析的数据处理需求。我们的建议 极大地改进了HRPF数据分析，取代了目前繁琐而令人苦恼的工作 使用集成的无缝解决方案来诠释和放大 居者有其屋计划研究。在我们设想的计划完成后，FoxWare将做出一个 在居屋分析上留下不可磨灭的印记，并在分析和 HRPF生产能力，满足生物制药行业的市场需求。