UAB Pilot Center for Precision Animal Modeling (C-PAM) - Preclinical/Co-Clinical Section

摘要(临床前/联合临床部分) 临床前/共同临床科(PCS)在受影响的个人和转诊之间提供了关键的联系 临床医生和C-PAM。指导原则是1)与受影响的个人保持对话，并推荐 临床医生确保有足够的信息可用来确定模型创建的优先顺序并验证 模式，以及2)让受影响的个人和转介临床医生作为合作伙伴，提供进展的最新情况 以负责任的方式。我们预计将收到几个正在进行的动物模型创建提名 UAB的计划，有一个现有的基因组变异队列进行分析，以及来自外部的来源 UAB的。PCS将提供一个安全的基于网络的通道，用于获取临床信息，这些信息通过 参与者的知情同意。PCS团队将审查这些信息并将其总结为PhenoTips 进入。这将被用来产生包括人类表型的变异表型包(VPP) 与受影响个体的表型相关的本体论术语以及相关的基因信息。那里 还将有能力获取和存储生物样本，如血液、尿液、唾液和外科手术 标本，如果需要的话。VPP将移交给生物信息科进行进一步分析，领导 最终是指导指导委员会决定是否建立一个模式的信息。一旦成为 一旦建立了模型，PCS将与疾病建模股合作，提供共同临床评估。 如果该模型可能表现出与受影响个体相似的表型，则PCS 将有助于根据临床表型对模型表型进行验证。通常，这需要返回到 受影响的个体或转诊临床医生，以获得额外的表型信息。在其他情况下，模型将 解决因基因组变异而改变的细胞功能。要进一步证实这一发现，可能需要额外的 对从患者身上获得的组织进行研究。PCS还将与疾病建模股合作 在潜在疗法的研究中。在某些情况下，可以识别出被识别的药物或物质 具有潜在的治疗益处。在其他情况下，模型的创建可能会使药物 探索的努力。在任何一种情况下，PCS都将与疾病建模单位合作，评估潜在的治疗方法。 如果结果揭示了一种变异的致病性或可能的治疗方法的可用性，这些将是 在与转介医生分享任何信息之前，由临床治疗委员会审查。 最终，如果得到委员会的批准，并且受影响的个人选择学习这些信息， PCS医生将与转诊医生进行沟通。否则，关于研究的一般信息 将在C-PAM门户上保持进展，以随时向受影响的个人和转诊医生通报情况 普遍的进步。

ABSTRACT (PRE/CO-CLINICAL SECTION) The Preclinical/Co-Clinical Section (PCS) provides a critical link between affected individuals and referring clinicians and the C-PAM. Guiding principles are 1) to maintain a dialog with affected individuals and referring clinicians to ensure that adequate information is available to prioritize creation of a model and to validate the model, and 2) to engage affected individuals and referring clinicians as partners, providing updates on progress in a responsible manner. We expect to receive nominations for creation of an animal model from several ongoing programs at UAB that have an existing queue of genomic variants for analysis, as well as from sources outside of UAB. The PCS will provide a secure web-based gateway for accession of clinical information, obtained with the informed consent of participants. The PCS team will review this information and summarize it in a PhenoTips entry. This in turn will be used to generate a Variant Phenopacket (VPP), which will include human phenotype ontology terms related to the affected individual's phenotype along with relevant genotypic information. There will also be the capacity to obtain and store biological samples, such as blood, urine, saliva, and surgical specimens, if needed. The VPP will be passed onto the Bioninformatics Section for further analysis, leading ultimately to information to guide a decision by the Steering Committee of whether to create a model. Once a model is made, the PCS will work together with the Disease Modeling Unit to provide co-clinical assessments. If the model is one that might demonstrate a phenotype similar to that seen in the affected individual, the PCS will help to validate the model phenotype in light of the clinical phenotype. Often this will require going back to the affected individual or referring clinician for additional phenotypic information. In other cases, the model will address cellular function altered by the genomic variant. Further validation of this finding might require additional studies in tissue obtained from the affected individual. The PCS will also work with the Disease Modeling Unit in studies of potential therapies. In some instances, a drug or substance might be identified that is recognized as having potential therapeutic benefit. In other instances, the creation of the model might enable a drug discovery effort. In either case, the PCS will work with the Disease Modeling Unit to assess potential therapies. If results shed light on the pathogenicity of a variant or on the availability of a possible treatment, these will be reviewed by a Clinical Curation Committee before any information is shared with the referring physician. Ultimately, if approved by the committee and the affected individual has opted into learning of such information, the PCS physician will communicate with the referring physician. Otherwise, general information on research progress will be maintained on the C-PAM portal to keep the affected individual and referring physician apprised of general progress.