Mount Sinai Regional Drug Induced Liver Injury Network Site

项目摘要 DILIN自成立以来的一个主要目标是识别预测 易患DILI，预后不良。DILIN已经确定了药物特效药和普通药 DILI易感性的生物标志物。这些遗传生物标记物中的大多数与人类白细胞抗原有关 等位基因。 在过去的几年里，尼科莱蒂博士一直在广泛地研究 药物导致肝脏损伤，最近加入了DILIN财团。尼科莱蒂医生已经 积极参与正在进行的根据人类白细胞抗原分析DILI病例的DILIN基因项目 等位基因和常见变种。她将继续发挥积极作用，执行正在进行的 Gwas和PrediXcan分析。鉴于她在预测人类白细胞抗原等位基因方面的丰富经验 算法使用了基因分型和测序数据，以及在 随后在HLA等位基因、单倍型和HLA超类型水平上进行了关联分析， 尼科莱蒂博士还指导设计/分析和解释DILIN的结果 与李博士、Chalasani博士、Barnhart博士、Dr. 菲利普斯和其他DILIN研究人员。适当的非帝力控制数据将对这些 学习。这些努力导致在过去的一年里出版了几本DILIN出版物，但额外的工作 还有很多事情要做。 在过去的一年里，尼科莱蒂博士戏剧性地扩大了她的努力，提供了非帝力控制数据 并调查DILI易感性与其他肝病之间的遗传联系。Dr。 尼科莱蒂处于独特的地位，可以立即接触到毒品和疾病 通过西奈山生物群生物库进行控制，这是最大的生物库之一，它已经配对 超过50,000人的遗传和临床数据。这个生物库的重量很大。 向肝病患者开放，因为肝科是第一个开放临床患者给 在BIOME中注册。最后，尼科莱蒂博士发现了帝力可能分担遗传风险的证据 其他自身免疫性肝病的因素，如原发性胆汁性肝硬变。通过组合DILIN 遗传数据与生物群数据集和其他适当的DBGaP数据集，她希望 评估DILI与其他肝病的遗传相似性，以便更好地了解 DILI的病理生理和遗传变异在自身免疫性状中的作用。 需要更多的时间和努力才能使这些研究取得成果。迪林要求 为尼科莱蒂博士的努力又提供了一年的补充支持。

Project Summary A major goal of DILIN since its inception has been to identify genetic biomarkers that predict predisposition to DILI and a poor prognosis. DILIN has identified both drug specific and general biomarkers for predisposition to DILI. The majority of these genetic biomarkers involve HLA alleles. In the last several years, Dr. Nicoletti has been working extensively on the predisposition to drug induced liver injury and recently joined the DILIN consortium. Dr. Nicoletti has been actively involved in the ongoing DILIN genetic projects that profiled DILI cases based on HLA alleles and common variants. She will continue to take an active role in carrying out the ongoing GWAS and PrediXscan analyses. Given her extensive experience on HLA allele prediction algorithms using both genotyped and sequencing data and extensive experience on the subsequent association analyses at the level of HLA alleles, haplotypes, and HLA supertypes, Dr. Nicoletti is also directing the design/analysis and interpretation of the results of the DILIN HLA allele sequencing project in collaboration with Dr. Li, Dr. Chalasani, Dr. Barnhart, Dr. Phillips and other DILIN researchers. Appropriate non-DILI control data will be critical to these studies. These efforts led to several DILIN publications in the past year, but additional work remains to be done. In the past year, Dr. Nicoletti expanded her efforts dramatically to provide non-DILI control data and investigate genetic links between predisposition to DILI and other liver diseases. Dr. Nicoletti is in the unique position of having immediate access to drug exposed and disease controls via the Mount Sinai BioME Biobank, one of the largest biobanks, which has paired genetic and clinical data for more than 50,000 individuals. This biobank is heavily weighted towards those with liver disease since the liver division was the first to open its clinic patients to enrollment in BioME. Finally, Dr. Nicoletti discovered evidence that DILI might share genetic risk factors with other autoimmune liver diseases like primary biliary cirrhosis. By combining DILIN genetic data with the BioMe dataset and other appropriate dbGAP datasets, she hopes to evaluate the genetic similarity between DILI and other liver disease in order to better understand the pathophysiology of DILI and the role of the genetic variants in the autoimmune traits. Additional time and effort is needed to bring these studies to fruition. DILIN is requesting another year of supplemental support for Dr. Nicoletti's efforts.