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

摘要（临床前/协同临床部分） 临床前/协同临床部分（PCS）提供了受影响个体和转诊之间的关键联系 临床医生和C-PAM。指导原则是：1）与受影响的个人保持对话， 临床医生确保有足够的信息可用于优先创建模型并验证 模型，以及2）让受影响的个人和转介临床医生作为合作伙伴，提供最新进展 以负责任的方式。我们希望从几个正在进行的动物模型创建中获得提名 UAB的程序，这些程序具有用于分析的基因组变体的现有队列，以及来自外部的来源 关于UAB PCS将提供一个安全的基于Web的网关，用于访问通过以下方式获得的临床信息 参与者的知情同意。PCS团队将审查这些信息，并将其总结在PhenoTips中。 入境这反过来将用于生成变体Phenopacket（VPP），其将包括人表型 与受影响个体的表型沿着相关基因型信息相关的本体术语。那里 也将是获取和存储生物样本的能力，如血液，尿液，唾液和手术 如果需要的话，还可以做标本。VPP将被传递到生物信息学部分进行进一步分析， 最终，指导委员会将信息用于指导是否创建模型的决定。一次 在制作模型后，PCS将与疾病模型组合作，提供临床评估。 如果该模型可能表现出与受影响个体相似的表型， 将有助于根据临床表型验证模型表型。这通常需要回到 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 解决由基因组变体改变的细胞功能。进一步验证这一发现可能需要额外的 从受影响的个体获得的组织中进行的研究。PCS还将与疾病建模股合作， 研究潜在的治疗方法。在某些情况下，可能会识别出一种药物或物质， 具有潜在的治疗益处。在其他情况下，模型的创建可能使药物 探索的努力在这两种情况下，PCS将与疾病建模部门合作，以评估潜在的治疗方法。 如果结果揭示了变异的致病性或可能的治疗方法的可用性， 在与转诊医生共享任何信息之前，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了解这些信息， PCS医生将与转诊医生进行通信。否则，研究的一般信息 将在C-PAM门户网站上保持进展，以通知受影响的个人和转诊医生 一般的进步。

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.