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Proteome TopFIND 3.0 with TopFINDer and PathFINDer: database and analysis tools for the association of protein termini to pre- and post-translational events.

Fortelny N, Yang S, Pavlidis P, Lange PF, Overall CM - Nucleic Acids Res. (2014)

Bottom Line: New features include the mapping of protein termini and cleavage entries across protein isoforms and significantly, the mapping of protein termini originating from alternative transcription and alternative translation start sites.Neo-termini are also linked to associated proteases.In re-capitulating the major findings originally performed manually, this validates the utility of these new resources.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada Centre for High Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada.

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Fragment of the graphviz figure of protease web connections identified by PathFINDer. Nodes are proteins, the query protease is marked in color and the proteins from the submitted list are gray. Edges are cleavages (arrows, with numbers for the position of the cleavage) or inhibitions (T shaped arrows, labeled as ‘inh’). Edges from TopFIND are solid and edges inferred from the list are dotted. Nodes from the complement system are marked with red.
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Figure 3: Fragment of the graphviz figure of protease web connections identified by PathFINDer. Nodes are proteins, the query protease is marked in color and the proteins from the submitted list are gray. Edges are cleavages (arrows, with numbers for the position of the cleavage) or inhibitions (T shaped arrows, labeled as ‘inh’). Edges from TopFIND are solid and edges inferred from the list are dotted. Nodes from the complement system are marked with red.

Mentions: We employ path-finding in the protease web to identify known direct and indirect explanations for the observed cleavages. This powerful analysis can reveal previously hidden dependencies, facilitate differentiation of direct and indirect effects and explain counter intuitive experimental results as show previously (12). With PathFINDer it is now possible to submit a list of identified human or mouse in vivo substrate candidates and cleavage sites and a candidate protease to find known direct and indirect connections (paths) from the protease to the identified substrates. By creating a representation of the protease web based on cleavage and inhibition data in TopFIND and then dynamically extending this network with connections from the candidate protease to the proteins in the list, PathFINDer identifies paths from the protease to each substrate. We expanded this analysis by cross-species mapping between human and mouse orthologous proteins to compensate for the currently sparse data, in particular in mouse (12). In this way if data are absent but present for homologues in the other species a reasonable prediction can still be formulated to test. This analysis can be run separately or in combination with a TopFINDer analysis. The identified paths are visualized in a network view (Figure 3) and listed in a tabular format (Supplementary Table S3) including links to all relevant proteins, cleavages and evidences in the TopFIND web interface.


Proteome TopFIND 3.0 with TopFINDer and PathFINDer: database and analysis tools for the association of protein termini to pre- and post-translational events.

Fortelny N, Yang S, Pavlidis P, Lange PF, Overall CM - Nucleic Acids Res. (2014)

Fragment of the graphviz figure of protease web connections identified by PathFINDer. Nodes are proteins, the query protease is marked in color and the proteins from the submitted list are gray. Edges are cleavages (arrows, with numbers for the position of the cleavage) or inhibitions (T shaped arrows, labeled as ‘inh’). Edges from TopFIND are solid and edges inferred from the list are dotted. Nodes from the complement system are marked with red.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383881&req=5

Figure 3: Fragment of the graphviz figure of protease web connections identified by PathFINDer. Nodes are proteins, the query protease is marked in color and the proteins from the submitted list are gray. Edges are cleavages (arrows, with numbers for the position of the cleavage) or inhibitions (T shaped arrows, labeled as ‘inh’). Edges from TopFIND are solid and edges inferred from the list are dotted. Nodes from the complement system are marked with red.
Mentions: We employ path-finding in the protease web to identify known direct and indirect explanations for the observed cleavages. This powerful analysis can reveal previously hidden dependencies, facilitate differentiation of direct and indirect effects and explain counter intuitive experimental results as show previously (12). With PathFINDer it is now possible to submit a list of identified human or mouse in vivo substrate candidates and cleavage sites and a candidate protease to find known direct and indirect connections (paths) from the protease to the identified substrates. By creating a representation of the protease web based on cleavage and inhibition data in TopFIND and then dynamically extending this network with connections from the candidate protease to the proteins in the list, PathFINDer identifies paths from the protease to each substrate. We expanded this analysis by cross-species mapping between human and mouse orthologous proteins to compensate for the currently sparse data, in particular in mouse (12). In this way if data are absent but present for homologues in the other species a reasonable prediction can still be formulated to test. This analysis can be run separately or in combination with a TopFINDer analysis. The identified paths are visualized in a network view (Figure 3) and listed in a tabular format (Supplementary Table S3) including links to all relevant proteins, cleavages and evidences in the TopFIND web interface.

Bottom Line: New features include the mapping of protein termini and cleavage entries across protein isoforms and significantly, the mapping of protein termini originating from alternative transcription and alternative translation start sites.Neo-termini are also linked to associated proteases.In re-capitulating the major findings originally performed manually, this validates the utility of these new resources.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada Centre for High Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada.

Show MeSH