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Updated: Jun 12, 2026
Identifying Caspases and their Motifs that Cleave Proteins During Influenza A Virus Infection
Published on: July 21, 2022
Pripper: prediction of caspase cleavage sites from whole proteomes
Mirva Piippo1, Niina Lietzén, Olli S Nevalainen
1Department of Information Technology, University of Turku, Turku, Finland. mirva.piippo@utu.fi
Background:
Caspases are a family of proteases that have central functions in programmed cell death (apoptosis) and inflammation. Caspases mediate their effects through aspartate-specific cleavage of their target proteins, and at present almost 400 caspase substrates are known. There are several methods developed to predict caspase cleavage sites from individual proteins, but currently none of them can be used to predict caspase cleavage sites from multiple proteins or entire proteomes, or to use several classifiers in combination. The possibility to create a database from predicted caspase cleavage products for the whole genome could significantly aid in identifying novel caspase targets from tandem mass spectrometry based proteomic experiments.
Results:
Three different pattern recognition classifiers were developed for predicting caspase cleavage sites from protein sequences. Evaluation of the classifiers with quality measures indicated that all of the three classifiers performed well in predicting caspase cleavage sites, and when combining different classifiers the accuracy increased further. A new tool, Pripper, was developed to utilize the classifiers and predict the caspase cut sites from an arbitrary number of input sequences. A database was constructed with the developed tool, and it was used to identify caspase target proteins from tandem mass spectrometry data from two different proteomic experiments. Both known caspase cleavage products as well as novel cleavage products were identified using the database demonstrating the usefulness of the tool. Pripper is not restricted to predicting only caspase cut sites, but it gives the possibility to scan protein sequences for any given motif(s) and predict cut sites once a suitable cut site prediction model for any other protease has been developed. Pripper is freely available and can be downloaded from http://users.utu.fi/mijopi/Pripper.
Conclusions:
We have developed Pripper, a tool for reading an arbitrary number of proteins in FASTA format, predicting their caspase cleavage sites and outputting the cleaved sequences to a new FASTA format sequence file. We show that Pripper is a valuable tool in identifying novel caspase target proteins from modern proteomics experiments.
Insights
We developed Pripper, a tool to predict caspase cleavage sites in proteins. This tool aids in identifying novel caspase targets in proteomic experiments, improving our understanding of apoptosis and inflammation.
Area of Science:
- Biochemistry
- Proteomics
- Bioinformatics
Background:
- Caspases are key proteases in apoptosis and inflammation, cleaving target proteins at aspartate residues.
- Over 400 caspase substrates are known, but predicting cleavage sites across proteomes remains challenging.
- Existing prediction methods are limited to single proteins and do not support combined classifier approaches.
Purpose of the Study:
- To develop a computational tool for predicting caspase cleavage sites in multiple protein sequences.
- To create a database of predicted caspase cleavage products for genome-wide analysis.
- To enhance the identification of novel caspase targets in proteomic studies.
Main Methods:
- Developed three pattern recognition classifiers for predicting caspase cleavage sites.
- Combined classifiers to improve prediction accuracy.
- Created the Pripper tool to process arbitrary numbers of protein sequences and predict cleavage sites.
Main Results:
- All developed classifiers demonstrated strong performance in predicting caspase cleavage sites.
- Combining classifiers further enhanced prediction accuracy.
- The Pripper tool successfully identified both known and novel caspase cleavage products from proteomic data.
- Pripper's utility extends to predicting cleavage sites for other proteases with suitable models.
Conclusions:
- Pripper is an effective tool for predicting caspase cleavage sites in multiple protein sequences.
- Pripper facilitates the identification of novel caspase targets in contemporary proteomics experiments.
- The tool is versatile, adaptable for predicting cleavage sites of other proteases.
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