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

Atlal El-Assaad, Zaher Dawy, Georges Nemer, Firas Kobeissy

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Title of host publication2015 IEEE International Conference on Electro/Information Technology, EIT 2015
PublisherIEEE Computer Society
Pages210-215
Number of pages6
ISBN (Electronic)9781479988020
DOIs
Publication statusPublished - 10 Jun 2015
Externally publishedYes
EventIEEE International Conference on Electro/Information Technology, EIT 2015 - Dekalb, United States
Duration: 21 May 201523 May 2015

Publication series

NameIEEE International Conference on Electro Information Technology
Volume2015-June
ISSN (Print)2154-0357
ISSN (Electronic)2154-0373

Conference

ConferenceIEEE International Conference on Electro/Information Technology, EIT 2015
Country/TerritoryUnited States
CityDekalb
Period21/05/1523/05/15

Keywords

  • Apoptosis
  • Biomarker
  • Breakdown Product (BDP)
  • Calpain
  • Caspase
  • Dynamic Programming
  • Necrosis
  • Oncosis
  • Proteolysis
  • αII-spectrin

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