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

摘要（协调部分） UAB精确动物建模试点中心（C-PAM）的愿景是成为一个国家级的 资源，以有效和具有成本效益的方式分析在罕见疾病患者中发现的基因变异的致病性 疾病和产生变异特异性模型，以追求疾病机制和靶向治疗。 由于全基因组的可用性，许多潜在的致病变异正在患者中被鉴定 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， 确认其致病性。在鉴定之后，这些变体需要评估和注释， 将没有影响的变体和简单的测序和定位错误与导致这些突变的变体分开。 疾病这是一个需要解决的复杂问题，需要采取跨学科的办法， 评估变量。这项工作的一部分是生成和分析信息丰富的动物模型。C-PAM具有 组建了一个由基础科学、计算和数据专业人员组成的高度协作的团队 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 团队已经建立了一个管道，在该管道中，将使用 由C-PAM生物信息学部分生成的创新生物信息学工具包。如果选中，则变量将 由C-PAM疾病建模单位在动物中建模。这些新模型将被评估为人类 C-PAM临床前/协同临床部分的疾病相关性。一旦产生，C-PAM将促进 专家合作，利用详细的信息分析和动物资源，将被分配 通过C-PAM资源和服务科，促进我们对疾病发病机制的理解， 确定新的或改变用途的治疗剂的功效，并有助于改善人类健康。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工作。这 是C-PAM协调科（CS）的工作，它将为 中心它将同步每个C-PAM组件的活动并提供管理， 行政支持和领导，以确保C-PAM组件正在努力实现一套共同的 目标. CS将召集监督委员会，以优先考虑提名的变体，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.