Unlocking the potential of the UK 100,000 Genomes Project-lessons learned from analysis of the "Congenital Malformations caused by Ciliopathies" cohort.
Unlocking the potential of the UK 100,000 Genomes Project-lessons learned from analysis of the "Congenital Malformations caused by Ciliopathies" cohort.
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DOI：
10.1002/ajmg.c.31965
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发表时间：
2022-03
影响因子：
3.1
通讯作者：
Johnson, Colin A.
中科院分区：
文献类型：
--
作者：
Best, Sunayna;Inglehearn, Chris F.;Watson, Christopher M.;Toomes, Carmel;Wheway, Gabrielle;Johnson, Colin A.
我们回顾了来自招募到英国100，000基因组计划（100 K）的“由纤毛病引起的先天性畸形”（CMC）队列的患者的测序、变体和临床数据（Best等人，2021年）。1通过使用纤毛病遗传学的领域特异性知识（Reiter & Leroux，2017; Wheway et al.，2019年），并检查非纤毛疾病基因的变异，我们能够识别出潜在的致病变异，超出了Genomics England（GEL，该公司成立运行100 K）实施的分类过程所报告的变异。因此，我们将诊断从GEL报告的27/83（32.5%）增加到43/83（51.8%）。在这项工作中，我们在访问和处理数据方面遇到了一些困难，并观察到目前可用数据集的一些局限性。在这里，我们回顾了这些问题，建议如何使10万数据更容易获得和更充分地利用患者的利益，并提出可以为未来的大规模人类基因组学研究所吸取的教训。这些问题被分为四大类：与招募个体可用的临床信息相关的问题;与变体的分类和优先级排序过程（所谓的“分层”）相关的问题;使用安全的GEL研究环境所遇到的困难;以及向招募临床医生报告相关研究结果的困难。
We reviewed sequencing, variant and clinical data from patients recruited to the “Congenital Malformations caused by Ciliopathies”(CMC) cohort of the UK 100,000 Genomes Project (100K)(Best et al., 2021). 1 By using domain-specific knowledge of ciliopathy genetics (Reiter & Leroux, 2017; Wheway et al., 2019), and examining variants in non-ciliopathy disease genes, we were able to identify potentially causative variants beyond those reported by the triaging process implemented by Genomics England (GEL, the company set up to run 100K). As a result, we increased diagnoses from the 27/83 (32.5%) that were reported by GEL, to 43/83 (51.8%). During this work, we experienced several difficulties in accessing and working with the data and observed several limitations with the currently available datasets. Here, we review these issues, suggest ways in which 100K data could be made more accessible and utilized more fully for patient benefit, and propose lessons that can be learned for future large-scale human genomics studies. The issues are grouped into four broad categories: those relating to the clinical information available for recruited individuals; issues relating to the triaging and prioritization process for variants (so-called “tiering”); difficulties experienced using the secure GEL research environment; and difficulties in reporting pertinent research findings back to recruiting clinicians.
影响因子：
4
作者：
通讯作者：
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DOI：
10.1038/nrm.2017.60
发表时间：
2017-09
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Reiter JF;Leroux MR
通讯作者：
Leroux MR
影响因子：
64.5
作者：
Jaganathan, Kishore;Panagiotopoulou, Sofia Kyriazopoulou;Farh, Kyle Kai-How
通讯作者：
Farh, Kyle Kai-How