Methods for follow-up research of exome analysis：外顯子後續分析研究思路總結
外顯子後續分析研究思路一般有以下幾種（Methods for follow-up research of exome analysis）：
1、對突變頻率、突變類型、突變方式進行統計分析
Mutations statistical analysis
具體見下圖：
參考文獻：Di, Jiabo, et al. "Whole exome sequencing reveals intertumor heterogeneity and distinct genetic origins of sporadic synchronous colorectal cancer." International journal of cancer
2、對變異的保守性進行評估
Conservation score calculation
一般用Genomic Evolutionary Rate Profiling這個網站進行保守性得分評估（網址：https://personal.broadinstitute.org/mgarber/GERP/documentation.pdf）
參考文獻：Wang, Binbin, et al. "Sequence variants of KHDRBS1 as high penetrance susceptibility risks for primary ovarian insufficiency by mis-regulating mRNA alternative splicing." Human Reproduction
3、目標基因在不同組織上表達度比較
Gene expression in different tissue
The Human Protein Atlas database 數據庫提供了基因在不同組織表達度比較的信息（網站地址：http://www.proteinatlas.org/）
參考文獻：Wang, Binbin, et al. "Sequence variants of KHDRBS1 as high penetrance susceptibility risks for primary ovarian insufficiency by mis-regulating mRNA alternative splicing." Human Reproduction
4、堿基覆蓋深度比較
默認理想情況下，堿基覆蓋度的深淺代表插入或缺失
Coverage depth calculation
gatk提供了堿基覆蓋度的計算，參數如下：
gatk堿基覆蓋度計算網址：
https://software.broadinstitute.org/gatk/documentation/tooldocs/current/org_broadinstitute_gatk_tools_walkers_coverage_DepthOfCoverage.php
參考文獻：Fedida, Joel, et al. "Contribution of exome sequencing for genetic diagnostic in arrhythmogenic right ventricular cardiomyopathy/dysplasia." PloS one 12.8 (2017): e0181840.
5、結構和功能分析
Structural and functional analysis in mutation
swissmodel網站提供了變異氨基酸導致結構變化的可視化界面（網站地址：https://swissmodel.expasy.org/）
使用方法詳見：蛋白質結構模型和功能預測：Swiss-model工具的使用
參考文獻：Bölükba??, Esra Y?ld?z, et al. "Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly." Journal of medical genetics (2017): jmedgenet-2017.
Methods for follow-up research of exome analysis：外顯子後續分析研究思路總結