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在阿斯巴拉金合成酶缺乏变体分类中AlphaMissense预测的实用性

Stephen J Staklinski^1,2, Armin Scheben¹, Adam Siepel¹

¹Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724.

bioRxiv : the preprint server for biology

|November 14, 2023

概括

AlphaMissense有效地对阿斯巴拉金合成酶缺乏症 (ASNSD) 的遗传变异进行了分类. 该工具通过预测变异病原性来帮助诊断ASNSD,为患者和家人提供清晰度.

科学领域:

遗传学是一个遗传学.
计算生物学计算生物学
生物化学生物化学

背景情况:

阿斯巴拉金合成酶缺乏症 (ASNSD) 是一种严重的发育障碍,与阿斯巴拉金合成酶 (ASNS) 基因突变有关.
准确地将ASNS变种分类为致病性或良性,对于ASNSD诊断至关重要.
当前的诊断方法需要强大的工具来解释变异.

研究的目的:

评估AlphaMissense的实用性,这是一个新型变异分类工具,用于阿斯巴拉金合成酶缺乏症 (ASNSD).
将AlphaMissense与已知的关键残留物和ASNS基因中报告的变异进行基准测试.
评估AlphaMissense在与ASNSD相关的致病变体分类方面的表现.

主要方法:

在ASNS活性部位和分子内道中对已知关键残留物进行AlphaMissense的基准测试.
评估AlphaMissense在之前报告的ASNSD相关变异的精选清单上的表现.
开发一个管道来计算任何UniProt蛋白的AlphaMissense分数.

主要成果:

对于已知的关键ASNS残留物,AlphaMissense赋予了高致病性得分.
该工具成功地将78.9%的已知的ASNSD相关误解变异分类为致病性.
其余的变种主要被归类为模两可的,只有少数被归类为良性的.

结论:

在疑似ASNSD病例中,AlphaMissense显示了对ASNS变异的分类有很大的潜力.
该工具可以加快诊断,并减少患者和家人的不确定性.
AlphaMissense为ASNSD的变体解释提供了一个宝贵的资源.

关键词:

阿尔法Missense的意思是错误的氨基酸是氨基酸中的一种.阿斯巴拉基因 (asparagine) 是一种遗传错误是我们天生的错误.代谢过程中的代谢.

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