TY - GEN
T1 - Cleaved Fragments Prediction Algorithm (CFPA) application to calpain and caspase in apoptosis and necrotic cell death
AU - El-Assaad, Atlal
AU - Dawy, Zaher
AU - Nemer, Georges
AU - Kobeissy, Firas
N1 - Publisher Copyright:
© 2015 IEEE.
PY - 2015/6/10
Y1 - 2015/6/10
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Biomarker
KW - Breakdown Product (BDP)
KW - Calpain
KW - Caspase
KW - Dynamic Programming
KW - Necrosis
KW - Oncosis
KW - Proteolysis
KW - αII-spectrin
UR - http://www.scopus.com/inward/record.url?scp=84975704399&partnerID=8YFLogxK
U2 - 10.1109/EIT.2015.7293342
DO - 10.1109/EIT.2015.7293342
M3 - Conference contribution
AN - SCOPUS:84975704399
T3 - IEEE International Conference on Electro Information Technology
SP - 210
EP - 215
BT - 2015 IEEE International Conference on Electro/Information Technology, EIT 2015
PB - IEEE Computer Society
T2 - IEEE International Conference on Electro/Information Technology, EIT 2015
Y2 - 21 May 2015 through 23 May 2015
ER -