UAB Pilot Center for Precision Animal Modeling (C-PAM) - Coordination Section

摘要(协调科) UAB精密动物建模试点中心(C-PAM)的愿景是成为全国 有效和经济高效地分析罕见疾病患者中发现的基因变异的致病性的资源 并制作特定变种的模型，以探索疾病机制和靶向治疗。 由于全基因组的可获得性，在患者身上发现了许多潜在的致病变异 测序技术。识别变异的速度现在远远超过了单个实验室的能力 确认它们的致病性。在确定之后，需要对这些变体进行评估和注释 将无影响且简单的测序和测绘错误的变体与导致 疾病。这是一个复杂的问题，需要跨学科的方法和协调一致的努力来解决 评估变种。这项工作的一部分是生成和分析提供信息的动物模型。C-PAM有 组建了一个团队，由具有基础科学、计算和数据专业知识的高度协作的人员组成 科学、人类遗传学、临床诊断和动物模型生成来解决这个问题。C-PAM 团队已经建立了一条管道，在其中社区提名的变体将使用 C-PAM生物信息科生成的创新生物信息学工具包。如果选中该选项，则变量将为 由C-PAM疾病模型组在动物身上建模。这些新模型将在人体内进行评估。 C-PAM临床前/联合临床科的疾病相关性。一旦生成，C-PAM将促进形成 专家协作，利用详细的信息分析和将被分发的动物资源 通过C-PAM资源和服务组，加深我们对疾病发病机制的了解，以 确定新的或重新调整用途的疗法的有效性，并为改善人类健康做出贡献。对于C-PAM 为了有效地开展工作并实现其目标，必须协调中心各组成部分的努力。这 C-PAM协调科(CS)的工作将为 中心。它将同步每个C-PAM组件的活动并提供管理， 管理支持和领导力，以确保C-PAM组件正在努力实现一套通用的 目标。政务司司长将成立监督委员会，对提名的变种进行优先排序，选择动物模型 评估C-PAM的性能和影响，并为中心制定战略计划 实现其愿景。

ABSTRACT (COORDINATION SECTION) The vision for the UAB Pilot Center for Precision Animal Modeling (C-PAM) is to become a national resource to efficiently and cost-effectively analyze pathogenicity of gene variants identified in patients with rare disorders and to produce variant-specific models to pursue disease mechanisms and targeted therapeutics. Many potential disease-causing variants are being identified in patients due to the availability of whole genome sequencing technologies. The pace of identifying variants is now far outpacing the ability for individual labs to confirm their pathogenicity. Following identification, these variants require assessment and annotation to separate variants of no impact and simple sequencing and mapping errors from those that are causative of the disease. This is a complex problem to address requiring interdisciplinary approaches and a concerted effort to evaluate the variant. Part of this effort is to generate and analyze informative animal models. C-PAM has assembled a team of highly collaborative individuals with expertise in basic science, computational and data sciences, human genetics, clinical diagnosis, and animal model generation to tackle this problem. The C-PAM team has established a pipeline in which community nominated variants will be thorough analyzed using an innovative bioinformatic toolkit generated by the C-PAM Bioinformatics Section. If selected, the variant will be modeled in animals by the C-PAM Disease Modeling Unit. These new models will be evaluated for human disease relevance by the C-PAM Pre/Co-clinical Section. Once generated, C-PAM will facilitate the formation of expert collaborations to utilize the detailed informatic analyses and the animal resource that will be distributed through the C-PAM Resource and Services Section to advance our understanding of disease pathogenesis, to ascertain efficacy of novel or repurposed therapeutics, and to contribute to improved human health. For C-PAM to work efficiently and achieve its goals, the efforts of each component in the Center must be coordinated. This is the job of the C-PAM Coordination Section (CS) that will provide the overall organizational structure for the Center. It will synchronize the activity of each of the C-PAM components and provide management, administrative support, and leadership to ensure C-PAM components are working toward a common set of objectives. The CS will assemble oversight committees to prioritize nominated variants, to select animal models for generation, to evaluate the performance and impact of C-PAM, and to make strategic plans for the Center to fulfill its vision.