Evolutionary decomposition & structural characterization of - - PowerPoint PPT Presentation
Evolutionary decomposition & structural characterization of functionally distinct protein isoforms Elodie Laine, Laboratory of Computational and Quantitative Biology Analytical Genomics team (dir. A. Carbone, www.lcqb.upmc.fr/AnalGenom/)
Elodie Laine, Laboratory of Computational and Quantitative Biology Analytical Genomics team (dir. A. Carbone, www.lcqb.upmc.fr/AnalGenom/)
Evolutionary decomposition & structural characterization
Gene
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Gene
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Transcription
mRNA transcripts Gene
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Transcription Translation
mRNA transcripts Protein isoforms Gene
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Alternative starts
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Alternative starts Mutually exclusive
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Alternative starts Mutually exclusive Insertion
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With many lines, the network may become quite complex!
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protein structure and interactions?
new functions in evolution? 5
ThorAxe PhyloSofS
To find orthologous exons To reconstruct transcripts’ phylogenies and predict isoforms’ 3D structures 6
7 Annotated transcripts
7 Splice graph Phylogenetic forest Annotated transcripts 3D model s-exon
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0 1 1 1 1 2 2 2 2 3 3 4 4 4 4 4 4
Predict structural features Search for structural templates Evaluate coverage Annotate s-exons Generate 3D models
Structural template search is performed in an iterative way and centered on s-exons.
#(templates) s-exon
First iteration
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0 1 1 1 1 2 2 2 2 3 3 4 4 4 4 4 4
Predict structural features Search for structural templates Evaluate coverage Annotate s-exons Generate 3D models
Structural template search is performed in an iterative way and centered on s-exons.
#(templates) s-exon
After 4 iterations
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Proline-rich regions, likely to be involved in interactions
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11 Template 4R8G
CAM-binding motifs s-exons
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% Q ) + 0 1 2 3 6 R 5 S 9 : T < = ? A 7 C D E F U V H I J K L M N O P 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 Number of templates by exons Exons Number of templates 0- 24.99% 25- 49.99% 50- 74.99% 75- 100%JNK family NEBL
13 50 human genes… ๏ belonging to 16 families ๏ across 12 species ๏ ~900 transcripts (Ensembl) ๏ [8-91] s-exons (ThorAxe)
13 50 human genes… ๏ belonging to 16 families ๏ across 12 species ๏ ~900 transcripts (Ensembl) ๏ [8-91] s-exons (ThorAxe) 69 conserved AS events involving 105 s-exons
Alter End Alter Start Exclusive tuple Insertion/ Deletion Described in the literature Not documented With structural information Not characterized
13 50 human genes… ๏ belonging to 16 families ๏ across 12 species ๏ ~900 transcripts (Ensembl) ๏ [8-91] s-exons (ThorAxe) 69 conserved AS events involving 105 s-exons
Alter End Alter Start Exclusive tuple Insertion/ Deletion Described in the literature Not documented With structural information Not characterized
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binding affinity (prot) binding affinity (RNA) binding specificity (DNA) cellular localization immunological recognition partner dissociation partner specificity regulation unknown
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DNA sequence specificity RNA binding affinity substrate binding partner dissociation
PAX6 FMR1 FYN TPM1
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๏ Transfer protein interaction annotations ๏ Characterize disordered regions ๏ Compare conformational preferences ๏ Include RNA-seq data to better estimate conservation levels ๏ Automatically detect events of interest in the splice graph
ThorAxe & PhyloSofS https://github.com/PhyloSofS-Team
Hugues Richard Diego Javier Zea Antoine Labeeuw Sofya Laskina Alexander Korzec Adel Ait-Hamlat Lélia Polit Analytical Genomics @LCQB Robert Koch Institut