Detection of Cystic Fibrosis Serological Biomarkers Using a T7 Phage Display Library

• Published in: Scientific reports Vol. 7; no. 1; pp. 17745 - 11
• Main Authors: Talwar, Harvinder, Hanoudi, Samer Najeeb, Geamanu, Andreea, Kissner, Dana, Draghici, Sorin, Samavati, Lobelia
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18-12-2017; Nature Publishing Group
• Subjects: 13; 13/1; 631/1647/2163; 692/4017; Adult; Alveoli; Antigens; Bacteriophage T7 - genetics; Bayes Theorem; Bayesian analysis; Biomarkers; Biomarkers - blood; Bronchus; Cell Surface Display Techniques - methods; Conductance; Cystic fibrosis; Cystic Fibrosis - blood; Cystic Fibrosis - genetics; Female; Gene Library; Hereditary diseases; High-Throughput Screening Assays - methods; Humanities and Social Sciences; Humans; Leukocytes; Lung cancer; Male; Middle Aged; mRNA; multidisciplinary; Peptide Library; Phage display; ROC Curve; Sarcoidosis; Sarcoidosis - genetics; Science; Science (multidisciplinary); Sensitivity and Specificity; Sweat
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-18041-2

Cystic fibrosis (CF) is an autosomal recessive disorder affecting the cystic fibrosis transmembrane conductance regulator (CFTR). CF is characterized by repeated lung infections leading to respiratory failure. Using a high-throughput method, we developed a T7 phage display cDNA library derived from mRNA isolated from bronchoalveolar lavage (BAL) cells and leukocytes of sarcoidosis patients. This library was biopanned to obtain 1070 potential antigens. A microarray platform was constructed and immunoscreened with sera from healthy (n = 49), lung cancer (LC) (n = 31) and CF (n = 31) subjects. We built 1,000 naïve Bayes models on the training sets. We selected the top 20 frequently significant clones ranked with student
t
-test discriminating CF antigens from healthy controls and LC at a False Discovery Rate (FDR) < 0.01. The performances of the models were validated on an independent validation set. The mean of the area under the receiver operating characteristic (ROC) curve for the classifiers was 0.973 with a sensitivity of 0.999 and specificity of 0.959. Finally, we identified CF specific clones that correlate highly with sweat chloride test, BMI, and FEV1% predicted values. For the first time, we show that CF specific serological biomarkers can be identified through immunocreenings of a T7 phage display library with high accuracy, which may have utility in development of molecular therapy.