外顯子剪接過程
The whole process is regulated by trans-acting elements such as SR proteins, heterogeneous nuclear ribonucleoproteins, and the regulatory complex. ESE, exonic splicing enhancer; ESS, exonic splicing silencer; ISE, intronic splicing enhancer; ISS, intronic splicing silencer; ss, splice site.
文章解讀
In silico prediction of splice-altering single nucleotide variants in the human genome
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267638/
拼接機制：
(i) splicing signals, including the 5′/3′ splice site and the branch point;
(ii) splicing regulatory elements, i.e. exonic/intronic splicing enhancers/silencers;
(iii) the spliceosome and other trans-acting elements that bind to cis-acting elements.
結(jié)論：
提出兩種集成學(xué)習(xí)方法，自適應(yīng)增強（AdaBoost）和隨機森林，被用于構(gòu)建改進(jìn)預(yù)測的新模型。
預(yù)先計算了人類基因組中所有潛在scSNV的整體評分，并將這兩個分?jǐn)?shù)及其相應(yīng)的注釋信息作成數(shù)據(jù)庫（dbscSNV）
dbscSNV數(shù)據(jù)庫（推薦使用）
以chr22的vcf測試
annovar注釋結(jié)果篩選值大于0.6的：
dbscsnv11 0.9833 22 19950045 19950045 T A het 116.77 22
dbscsnv11 0.9465 22 22049783 22049783 C T het 151.77 14
對于內(nèi)含子內(nèi)部的位點，目前軟件很難預(yù)測準(zhǔn)確，當(dāng)懷疑為內(nèi)含子突變引起的可變剪切時，也許可做一個RNA逆轉(zhuǎn)錄。
其他在線識別剪接工具
GeneSplicer
http://www.cbcb.umd.edu/software/GeneSplicer/gene_spl.shtml
HumanSplicingFinder
http://www.umd.be/HSF/
NetGene2
http://www.cbs.dtu.dk/services/NetGene2
NNSplice
http://www.fruitfly.org/seq_tools/splice.html
FSPLICE
http://www.softberry.com/berry.phtml?topic=fsplice&group=programs&subgroup=gfind
Augustus
http://bioinf.uni-greifswald.de/augustus/submission.php
SPANR：
http://tools.genes.toronto.edu
HSF3：
http://umd.be/HSF3/
補充文章：InterVar: Clinical Interpretation of Genetic Variants by the 2015 ACMG-AMP Guidelines
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294755/
InterVar：2015年ACMG-AMP指南對遺傳變異的臨床解釋
對用ANNOVAR生成突變注釋信息進(jìn)行了解釋并有特定的打分，最后歸為五層分類系統(tǒng)
ACMG和AMP以來自不同數(shù)據(jù)共28個標(biāo)準(zhǔn)，推薦遺傳變異使用五層分類系統(tǒng)：pathogenic, likely pathogenic, uncertain significance, likely benign, and benign
