Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
Mol Syst Biol. 2024 Jul;20(7):741-743. doi: 10.1038/s44320-024-00044-7. Epub 2024 Jun 7.
Advances in high-throughput functional genomics have enabled researchers to measure many thousands of individual genetic variants in a single gene in parallel using techniques such as deep mutational scanning (Fowler and Fields, 2014). The success of these approaches depends on the availability of assays that can measure a wide range of protein functions. In their recent work, Kudla and colleagues (McDonnell et al, 2024) applied deep mutational scanning to the transcription factor , which has a key role in eye development, and described a new high-throughput functional assay that could be applied to almost any transcription factor. The authors successfully measured the effects of 95% of missense variants in PAX6 and show that their assay results are highly concordant with known clinical variants. Notably, they also undertook a wide-ranging survey of computational variant effect predictors and show that their experimental data outperformed cutting-edge algorithms.
高通量功能基因组学的进展使研究人员能够使用深度突变扫描等技术（Fowler 和 Fields，2014）同时平行测量单个基因中的数千个个体遗传变异。这些方法的成功取决于是否有能够测量广泛蛋白质功能的检测方法。在最近的工作中，Kudla 和同事（McDonnell 等人，2024）将深度突变扫描应用于转录因子，该因子在眼睛发育中起关键作用，并描述了一种新的高通量功能检测方法，几乎可以应用于任何转录因子。作者成功地测量了 PAX6 中 95%的错义变异的影响，并表明他们的检测结果与已知的临床变异高度一致。值得注意的是，他们还对计算变异效应预测器进行了广泛的调查，并表明他们的实验数据优于最先进的算法。
