2021.11.20 [reading notes] | differential variable splicing events and DTU analysis

• One 、 Variable splicing (Alternative Splicing)
  • Definition ：
    • Same precursor mRNA molecular , Splicing reactions can occur at different splicing sites , Generate different mRNA molecular , One that eventually produces different protein molecules RNA Cut way .
  • significance ：
    • 1. AS It is one of the important reasons for the formation of biodiversity
    • 2. AS It is an important part of gene expression regulation , It is closely related to the spatiotemporal nature of gene expression
    • 3. Due to the variable splicing, the expression products are different , So alternative splicing in some traits 、 Play an important role in diseases .
  • distinguish ：
    • Divided into 7 A type of

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  • Identification tools ：
    • SUPPA,# It has been upgraded to SUPPA2
    • 1. Short calculation time . Little data , The calculation can be completed in a few minutes .

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    • 2. Identifying alternative splicing boundaries is strict .

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    • 3. The results can be displayed visually , It can also be further analyzed later .
• Two 、 Differential alternative splicing ：DAS
  • Research significance

    • 

    • 1. Focus on finding that when the external environment changes , Variable splicing events in which significant changes in expression were found .
    • 2. These alternative splicing events may be more adaptive （ Or even worse ） New environmental conditions .
    • 3. But when we study the whole amount of gene expression , This change in the amount of expression of a particular structure may be masked .
    • PSI

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      • computing method
        • FPKM And TPM Value calculation difference
        • PSI value =split_in/(split_in+split_out)（TPM value ）

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      • PSI Significance test method （ A little ）
      • Follow up analysis
        • technological process

          

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      • Screening criteria
        • |dPsi|>0.1, P-value<0.05
• 3、 ... and 、DAS Analyze examples
  • 1.DAS Application ：
    • The literature ：Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks
    • (https://genome.cshlp.org/content/26/6/732.full)
    • Periodical ：Genome Research
    • Influencing factors ：11.351
    • Time of publication ：2016 year
  • 2. research objective ： Research 11 In cancer , The change of the types of alternative splicing and its application in RNA Enrichment of binding domain of binding protein .
  • 3. speculation ： In cancer ,RBP gene （RNA Protein binding genes ） Mutations may be associated with abnormal alternative splicing patterns .
  • 4. The analysis is as follows ：
    • ①11 Middle cancer ,DAS Type distribution of ;
    • ② stay cancer-drivers in ,DAS And gene mutation and differential expression ;
    • ③ stay RBP In gene ,DAS And gene mutation and expression ;
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  • 5. summary
    • 1. The literature found that ： In the study of 11 Of the three types of cancer ,DAS In many cancers cancer-drivers Middle scores are common ;
    • 2. stay cancer-drivers in ,DAS There is no necessary relationship between the occurrence and mutation or the change of expression ;
    • 3. stay RBPs in ,DAS It is highly distributed in some cancer types ;
    • 4. It happened in RBPs Medium DAS, There was no significant correlation with the amount of expression , But there may be a potential relationship with mutation ;
    • 5. Some cancers may have potential regulation DAS The common mechanism of .
• Four 、DTU Introduction to analysis
  • 1.DTU：Different Transcript Usage
  • 2.DTU The meaning of analysis ： Many complex structural changes may occur simultaneously in the same transcript , At this time , Focus on the overall changes of this transcript rather than a specific alternative splicing .
  • 3.DAS And DTU The difference between ：DAS It focuses on analyzing the difference of a specific alternative splicing event under different conditions ; and DTU Do not focus solely on a mutable splicing event , Instead, it focuses on the whole transcript where alternative splicing has occurred .
    • 1. Mainly for the structural variation types 、 Complex transcripts .
    • 2. Ignore the effect of gene expression , More targeted to find transcripts that respond to environmental changes .
    • 3. Three generations of full-length transcripts have obvious advantages in detecting structural variation , For transcripts with complex structure and response to environmental changes , It has obvious research advantages .

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  • summary
    • 1.SUPPA The identification of alternative splicing types is complete , And the results are shown in detail .
    • 2.DAS analysis , At the level of expression , To dig deeper into the biological significance of alternative splicing .
    • 3.DTU And DAS The research methods are similar , The main difference is that the objects of study are different .
    • 4.DAS/DTU Subsequent studies may increase enrichment 、 Comments, etc , More in-depth discussion of difference Events / The potential function of transcripts .
• The above content comes from the sorting of Nuohe course notes
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