Proteomic investigation of falciparum and vivax malaria for identification of surrogate protein markers.
This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.
Wadhwani Research Center for Biosciences and Bioengineering, Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, India.
Sandipan
S
Ray
Durairaj
D
Renu
Rajneesh
R
Srivastava
Kishore
K
Gollapalli
Santosh
S
Taur
Tulip
T
Jhaveri
Snigdha
S
Dhali
Srinivasarao
S
Chennareddy
Ankit
A
Potla
Jyoti Bajpai
JB
Dikshit
Rapole
R
Srikanth
Nithya
N
Gogtay
Urmila
U
Thatte
Swati
S
Patankar
Sanjeeva
S
Srivastava
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood*; D016780:Malaria, Vivax / Q000097:blood*; D008875:Middle Aged; D015233:Models, Statistical; D010641:Phenotype; D060066:Protein Interaction Maps; D040901:Proteomics; D059467:Transcriptome; D055815:Young Adult
D015415:Biomarkers; D001798:Blood Proteins