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

基本信息

批准号：
10092185
负责人：
Scot Randy Weinberger
金额：
$ 49.22万
依托单位：
GENNEXT TECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
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/10092185
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 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

项目摘要

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.

GenNext 第二阶段 SBIR 提交的题为“FoxWare™，一种高级数据羟基自由基足迹高阶结构分析的分析包”是满足对新的和改进的更高阶工具的公认需求生物制药的结构分析（HOS）非常复杂， 3维生物分子的异质混合物，其安全性和有效性依赖于正确的 HOS 与不正确的 HOS 蛋白质的存在有关。严重药物不良反应（ADR），确定需要新的和改进的居屋分析。一种新兴的 HOS 分析技术是羟基自由基足迹 (HRPF)。 HRPF 涉及通过与羟基反应对蛋白质外部进行不可逆标记通过随后的 MS 分析来识别自由基，以识别蛋白质的外部部分。最广泛使用的产生 OH 自由基的方法采用快速爆发的紫外线，被适当地称为蛋白质快速光化学氧化（FPOP）。实验室已经证明了 FPOP 在 HOS 分析中的实用性；但采用情况如何？在领先科学家的批评的指导下，制药业的影响充其量是微不足道的。对于生物制药公司，我们已经发现了限制制药公司发展的障碍采用 FPOP HRPF 的一个重大障碍是缺乏数据处理。目前还没有用于 FPOP 的商业解决方案。尽管市场对其 HOS 分析能力的需求已得到证实。当今的蛋白质组数据分析产品无法充分解决特定问题 HRPF 的工作流程、化学标记/工件和比较研究要求研究人员不得不艰难地采用零碎的方法。将多个包的结果拼接在一起并手动操作数据因此，数据处理是一个重要的瓶颈。这极大地复杂化并延迟了我们的 FoxWare™ 研究的进展。软件满足 HRPF HOS 分析的数据处理需求。通过取代当今费力且痛苦的方法，极大地改进了 HRPF 数据分析通过集成、无缝的解决方案来解释和放大价值的实践 HRPF HOS 研究完成后，FoxWare 将制定一份报告。居屋分析中不可磨灭的印记，并赋予分析和分析方面的变革性转变 HRPF通量，满足生物制药行业的市场需求。