title: CASH: a constructing comprehensive splice site method for detecting alternative splicing events.
abstract: RNA-sequencing (RNA-seq) can generate millions of reads to provide clues for analyzing novel or abnormal alternative splicing (AS) events in cells. However, current methods for exploring AS events are still far from being satisfactory. Here, we present Comprehensive AS Hunting (CASH), which constructs comprehensive splice sites including known and novel AS sites in cells, and identifies differentially AS events between cells. We illuminated the versatility of CASH on RNA-seq data from a wide range of species and also on simulated in silico data, validated the advantages of CASH over other AS predictors and exhibited novel differentially AS events. Moreover, we used CASH to identify SRSF10-regulated AS events and investigated the evolution of SRSF10-regulated splicing. The results showed that SRSF10-regulated splicing events are highly evolvable from chickens, mice to humans. However, SRSF10-regulated splicing model was observed to be immutable, in which SRSF10 binding to cassette exon promotes exon inclusion while binding to downstream exon induces exon skipping. Altogether, CASH can significantly improve the detection of AS events and facilitate the study of AS regulation and function in cells; the SRSF10 data first demonstrate a flexibility of SRSF10 with their regulated splicing events but an immutability of SRSF10-regulated splicing model to produce opposite AS outcomes in vertebrates.
authors.affiliation: The State Key Laboratory of Subtropical Silviculture, Zhejiang A & F University, Lin'an, Hangzhou, China.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Wu
authors.affiliation: Novel Bioinformatics Co., Ltd, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zong
authors.affiliation: Institute for Nutritional Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wei
authors.affiliation: Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences (CAS), Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Tianjin Medical University General Hospital, China.
authors.forename: Xuexia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Institute for Nutritional Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Novel Bioinformatics Co., Ltd, Shanghai, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Chen
authors.affiliation: Novel Bioinformatics Co., Ltd, Shanghai, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Novel Bioinformatics Co., Ltd, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Institute for Nutritional Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002645:Chickens; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D005091:Exons; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods / Q000706:statistics & numerical data; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D022821:RNA Splice Sites; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA / Q000379:methods / Q000706:statistics & numerical data; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics / Q000378:metabolism; D012984:Software
chemical_list: D018797:Cell Cycle Proteins; D022821:RNA Splice Sites; D012097:Repressor Proteins; C115188:SRSF10 protein, human; C000599974:SRSF10 protein, mouse; D000068103:Serine-Arginine Splicing Factors