Title
Cascleave 2.0, a new approach for predicting caspase and granzyme cleavage targets.
Abstract
Motivation: Caspases and granzyme B (GrB) are important proteases involved in fundamental cellular processes and play essential roles in programmed cell death, necrosis and inflammation. Although a number of substrates for both types have been experimentally identified, the complete repertoire of caspases and granzyme B substrates remained to be fully characterized. Accordingly, systematic bioinformatics studies of known cleavage sites may provide important insights into their substrate specificity and facilitate the discovery of novel substrates. Results: We develop a new bioinformatics tool, termed Cascleave 2.0, which builds on previous success of the Cascleave tool for predicting generic caspase cleavage sites. It can be efficiently used to predict potential caspase-specific cleavage sites for the human caspase-1, 3, 6, 7, 8 and GrB. In particular, we integrate heterogeneous sequence and protein functional information from various sources to improve the prediction accuracy of Cascleave 2.0. During classification, we use both maximum relevance minimum redundancy and forward feature selection techniques to quantify the relative contribution of each feature to prediction and thus remove redundant as well as irrelevant features. A systematic evaluation of Cascleave 2.0 using the benchmark data and comparison with other state-of-the-art tools using independent test data indicate that Cascleave 2.0 outperforms other tools on protease-specific cleavage site prediction of caspase-1, 3, 6, 7 and GrB. Cascleave 2.0 is anticipated to be used as a powerful tool for identifying novel substrates and cleavage sites of caspases and GrB and help understand the functional roles of these important proteases in human proteolytic cascades.
Year
DOI
Venue
2014
10.1093/bioinformatics/btt603
BIOINFORMATICS
Field
DocType
Volume
Proteases,Biology,Cell biology,Granzyme,Bioinformatics,Granzyme B,Caspase,Inflammation,Programmed cell death,Cleavage (embryo)
Journal
30
Issue
ISSN
Citations 
1
1367-4803
14
PageRank 
References 
Authors
0.67
28
6
Name
Order
Citations
PageRank
Mingjun Wang1341.44
Xing-Ming Zhao229320.55
Hao Tan3371.60
Tatsuya Akutsu42169216.05
James C Whisstock5937.90
Jiangning Song637441.93