NDLI: Cleaved Fragments Prediction Algorithm (CFPA) application to calpain and caspase in apoptosis and necrotic cell death

Content Provider	IEEE Xplore Digital Library
Author	El-Assaad, A. Dawy, Z. Nemer, G. Kobeissy, F.
Copyright Year	2015
Description	Author affiliation: Dept. of Biochem. & Mol. Genetics, American Univ. of Beirut, Riad El Solh, Lebanon (Nemer, G.; Kobeissy, F.) \|\| Dept. of Electr. & Comput. Eng., American Univ. of Beirut, Beirut, Lebanon (El-Assaad, A.; Dawy, Z.)
Abstract	The activation of cysteine proteases, calpain and caspase-3, which orchestrate the two major types of cell death, necrosis and apoptosis in various neurological and neurodegenerative disorders, drive cleavage of susceptible cellular proteins whose Breakdown Products (BDPs) can be utilized as biochemical markers; these markers can distinguish the molecular root causes among different types of neural cell death. There is an immense need to make such distinction between calpain and caspase-dependant dominated types of cell injury which is crucial in order to identify the injury mechanisms; thus, creating opportunities for neurotherapy development. Calpain protease is activated in various necrotic and apoptotic conditions generating calpain-specific cleaved fragments, while caspase-3 is predominantly activated in neuronal apoptosis generating caspase-3-specific cleaved fragments. Yet, despite the difference in cleavage specificity between calpain and caspase, some cellular proteins are dually susceptible to both proteases in some neurotoxic challenges such as hypoxia-hypoglycemia and excitotoxin treatment. During their activation, it is difficult to identify the resulting fragments despite the advanced experimental proteomics techniques in the field of degradomics. Current approaches rely on experimental techniques involving western blotting technique coupled with protein sequencing to identify the sequence specific and fragmentation site of the specific BDP(s). The main purpose of this work is to establish a new efficient and accurate methodological tool based on dynamic programming to predict those BDPs computationally with an algorithm of space complexity O(mn) and time complexity O(NN'mn), where the comprised parameters correspond to number of protein sequences, number of consensus sequences, length of each protein sequence, and length of each consensus sequence, respectively. The current algorithm is based on a modification of the Cleaved Fragments Prediction Algorithm (CFPA) and achieves high homology with experimental results.
Starting Page	210
Ending Page	215
File Size	2662573
Page Count	6
File Format	PDF
ISSN	21540373
e-ISBN	9781479988020
DOI	10.1109/EIT.2015.7293342
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2015-05-21
Publisher Place	USA
Access Restriction	Subscribed
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	Protein sequence Electric breakdown Heuristic algorithms Prediction algorithms Algorithm design and analysis Substrates Dynamic Programming Calpain Caspase αII-spectrin Breakdown Product (BDP) Apoptosis Oncosis Necrosis Proteolysis Biomarker
Content Type	Text
Resource Type	Article

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