Cascleave 2.0, a new approach for predicting caspase and granzyme cleavage targets

Mingjun Wang, Xing-Ming Zhao, Hao Tan, Tatsuya Akutsu, James Whisstock, Jiangning Song

Research output: Contribution to journalArticleResearchpeer-review

36 Citations (Scopus)

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.Availability and implementation: http://www.structbioinfor.org/cascleave2/. CONTACT: Jiangning.Song@monash.edu or James.Whisstock@monash.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Original languageEnglish
Pages (from-to)71 - 80
Number of pages10
JournalBioinformatics
Volume30
Issue number1
DOIs
Publication statusPublished - 2014

Cite this

Wang, Mingjun ; Zhao, Xing-Ming ; Tan, Hao ; Akutsu, Tatsuya ; Whisstock, James ; Song, Jiangning. / Cascleave 2.0, a new approach for predicting caspase and granzyme cleavage targets. In: Bioinformatics. 2014 ; Vol. 30, No. 1. pp. 71 - 80.
@article{5dc572b0d6b245e3ab2ba2b2b59d55ad,
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.Availability and implementation: http://www.structbioinfor.org/cascleave2/. CONTACT: Jiangning.Song@monash.edu or James.Whisstock@monash.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.",
author = "Mingjun Wang and Xing-Ming Zhao and Hao Tan and Tatsuya Akutsu and James Whisstock and Jiangning Song",
year = "2014",
doi = "10.1093/bioinformatics/btt603",
language = "English",
volume = "30",
pages = "71 -- 80",
journal = "Bioinformatics",
issn = "1367-4803",
publisher = "Oxford University Press, USA",
number = "1",

}

Cascleave 2.0, a new approach for predicting caspase and granzyme cleavage targets. / Wang, Mingjun; Zhao, Xing-Ming; Tan, Hao; Akutsu, Tatsuya; Whisstock, James; Song, Jiangning.

In: Bioinformatics, Vol. 30, No. 1, 2014, p. 71 - 80.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Cascleave 2.0, a new approach for predicting caspase and granzyme cleavage targets

AU - Wang, Mingjun

AU - Zhao, Xing-Ming

AU - Tan, Hao

AU - Akutsu, Tatsuya

AU - Whisstock, James

AU - Song, Jiangning

PY - 2014

Y1 - 2014

N2 - 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.Availability and implementation: http://www.structbioinfor.org/cascleave2/. CONTACT: Jiangning.Song@monash.edu or James.Whisstock@monash.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

AB - 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.Availability and implementation: http://www.structbioinfor.org/cascleave2/. CONTACT: Jiangning.Song@monash.edu or James.Whisstock@monash.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

UR - http://bioinformatics.oxfordjournals.org/content/30/1/71.full.pdf+html

U2 - 10.1093/bioinformatics/btt603

DO - 10.1093/bioinformatics/btt603

M3 - Article

VL - 30

SP - 71

EP - 80

JO - Bioinformatics

JF - Bioinformatics

SN - 1367-4803

IS - 1

ER -