A cell culture management platform to improve biomedical reproducibility by combining cell line tracking, low-cost genetic analysis, and riskassessment

细胞培养管理平台，通过结合细胞系追踪、低成本遗传分析和风险评估来提高生物医学重现性

• 批准号: 10483063
• 负责人: Sophie Zaaijer
• 金额: $ 25.92万
• 依托单位: FIND GENOMICS INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2023-09-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483063
• 关键词: Address; Adoption; Assessment tool; Behavior; Behavioral; Benchmarking; Biological; Biomedical Research; Budgets; Cancer cell line; Cell Culture Techniques; Cell Line; Cell Lineage; Cells; Cellular Morphology; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Communication; Communities; Computer software; Computing Methodologies; Consumption; DNA; DNA sequencing; Data; Ensure; Evolution; Feedback; Fill-It; Friction; G-Banding; Genetic; Genetic Identity; Genome; Genome engineering; Genomics; Gold; Grant; Human Cell Line; In Vitro; Individual; Institution; Intuition; Investments; Journals; Karyotype determination procedure; Link; Maintenance; Manuscripts; Measures; Metadata; Methods; Modeling; Patient Self-Report; Performance; Phase; Population; Positioning Attribute; Protocols documentation; Reporting; Reproducibility; Research; Research Personnel; Resources; Risk; Risk Assessment; Savings; Scientist; Service delivery model; Services; Small Business Innovation Research Grant; Standardization; System; Technology; Test Result; Testing; Time; United States National Institutes of Health; Variant; Work; base; bioinformatics pipeline; biological research; cell type; cohort; cost; design; experimental study; genetic analysis; genome sequencing; graphical user interface; improved; innovation; interoperability; multidimensional data; new technology; next generation; pre-clinical research; programs; prototype; recruit; response; software as a service; software development; software infrastructure; stem cells; support tools; tool; usability; user-friendly; wasting; whole genome

PROJECT SUMMARY Irreproducibility of biomedical and preclinical research is responsible for wasting 50% of the entire research budget and accounts for billions of wasted dollars. Issues with authenticity of key resources, such as cell lines, form a major contributor to this problem. An alarming increase in cell authenticity issues has prompted the NIH and some journals to take action by requiring grant applicants to discuss plans for authentication and requiring manuscript authors to report authentication results. However, the current gold standards for cell authentication are costly and time consuming. They present significant hurdles for researchers, leading to avoidance of testing. Other factors that exacerbate the problem of irreproducibility include a lack of systematic reporting on provenance details regarding passaging, maintenance protocols, chain-of-custody, and relational lineage information. The tools available nowadays are not specifically created for cell culture and lack interoperability. This increases the burden on reporting and reduces transparency. To address these unmet needs, FIND Genomics is developing FIND Cell, a comprehensive cell culture management platform. The primary innovation of this platform is the integration of three key components: 1) a collaborative, multidimensional data organization tool for cell culture work (e.g., graphical user interface designed to facilitate tracking of cell lines across lineages), 2) risk assessment capabilities, and 3) a computational method to assess cell quality (both genetic identity and stability) that provides users with the option of using low-coverage whole-genome sequencing. Use of our tool will save scientists time and costs associated with ensuring cell quality. We have developed a prototype that has been tested and graded as “Excellent” by cell experts. To bring FIND Cell to market, we aim to developing our software as outlined in this Direct-to-Phase II SBIR project proposal: AIM 1. Benchmark our low-cost, high- accuracy cell quality analysis through comparison with gold standards (STR typing and G-band karyotyping); AIM 2. Develop a cell line risk assessment and decision support tool; AIM 3. Refine our management platform’s user interface, and calculate operational savings based on user feedback. Successful completion of this project will result in a market-ready, user-friendly platform with a validated method for cell authentication. Additionally, our platform will include predictive risk analysis that will alert users. The early warning system, combined with cheap and easy authentication, will reduce waste of time, effort and money on experiments with faulty cell lines. The ease of record-keeping and -sharing in a single interface will enable transparency and rigor and improve reproducibility in biomedical/preclinical research.

项目概要 生物医学和临床前研究的不可重复性导致整个研究的 50% 被浪费 预算并浪费了数十亿美元的关键资源的真实性问题，例如细胞系， 细胞真实性的惊人增加引发了 NIH 的问题。 一些期刊采取行动，要求资助申请人讨论认证计划并要求 稿件作者报告验证结果 然而，当前的细胞验证黄金标准。 它们成本高昂且耗时，给研究人员带来了重大障碍，导致他们无法进行测试。 加剧不可重复性问题的其他因素包括缺乏系统的报告 有关传递、维护协议、监管链和关系谱系的来源详细信息 目前可用的工具并不是专门为细胞培养而创建的，并且缺乏互操作性。 这增加了报告负担并降低了透明度。为了解决这些未满足的需求，FIND。 Genomics 正在开发 FIND Cell，这是一个综合性细胞培养管理平台的主要创新。 该平台集成了三个关键组件：1）协作的多维数据组织 用于细胞培养工作的工具（例如，旨在促进跨谱系跟踪细胞系的图形用户界面）， 2) 风险评估能力，以及 3) 评估细胞质量（遗传特性和细胞质量）的计算方法 稳定性），为用户提供使用低覆盖率全基因组测序的选择。 将节省科学家与确保细胞质量相关的时间和成本。 已被细胞专家测试并评为“优秀” 为了将 FIND Cell 推向市场，我们的目标是开发我们的产品。 直接进入第二阶段 SBIR 项目提案中概述的软件：AIM 1。对我们的低成本、高成本进行基准测试 通过与金标准比较（STR 分型和 G 带核型分析）进行准确的细胞质量分析； AIM 2. 开发细胞系风险评估和决策支持工具 AIM 3. 完善我们的管理平台； 用户界面，并根据用户反馈计算成功完成该项目的运营节省。 将形成一个市场就绪、用户友好的平台，并具有经过验证的细胞认证方法。 我们的平台将包括预测风险分析，并结合预警系统向用户发出警报。 廉价且易于验证，将减少在有缺陷的细胞系实验上浪费时间、精力和金钱。 在单一界面中轻松保存和共享记录将实现透明度和严谨性，并改善 生物医学/临床前研究的可重复性。