title: Exploiting heterogeneous features to improve in silico prediction of peptide status - amyloidogenic or non-amyloidogenic.
abstract: BACKGROUND
  Prediction of short stretches in protein sequences capable of forming amyloid-like fibrils is important in understanding the underlying cause of amyloid illnesses thereby aiding in the discovery of sequence-targeted anti-aggregation pharmaceuticals. Due to the constraints of experimental molecular techniques in identifying such motif segments, it is highly desirable to develop computational methods to provide better and affordable in silico predictions.
  
  
  RESULTS
  Accurate in silico prediction techniques of amyloidogenic peptide regions rely on the cooperation between informative features and classifier design. In this research article, we propose one such efficient fibril prediction implementation exploiting heterogeneous features based on bio-physio-chemical (BPC) properties, auto-correlation function of carefully selected amino acid indices and atomic composition within a protein fragment of amino acids in a window. In an attempt to get an optimal number of BPC features, an evolutionary Support Vector Machine (SVM) integrating a novel implementation of hybrid Genetic Algorithm termed Memetic Algorithm and SVM is utilized. Five prediction modules designed using Artificial Neural Network (ANN) models are trained with independent and integrated features in order to validate the fibril forming motifs. The results provide evidence that incorporating new feature namely auto-correlation function besides BPC, attempt to strengthen the sequence interaction effect in forming the feature vector thereby obtaining better prediction quality in terms of sensitivity, specificity, Mathews Correlation Coefficient and Area under the Receiver Operating Characteristics curve.
  
  
  CONCLUSIONS
  A significant improvement in performance is observed by introducing features like auto-correlation function that maintains sequence order effect, in addition to the conventional BPC properties selected through a novel optimization strategy to predict the peptide status - amyloidogenic or non-amyloidogenic. The proposed approach achieves acceptable results, comparable to most online predictors. Besides, it compensates the lacuna in existing amyloid fibril prediction tools by maintaining equilibrium between sensitivity and specificity.
authors.affiliation: Department of Computer Science and Engineering, Manipal Institute of Technology, Manipal University, Karnataka, India. smitha.sunil@manipal.edu
authors.forename: Smitha Sunil Kumaran
authors.initials: SS
authors.lastname: Nair
authors.forename: N V
authors.initials: NV
authors.lastname: Subba Reddy
authors.forename: K S
authors.initials: KS
authors.lastname: Hareesha
mesh_terms: D000465:Algorithms; D000682:Amyloid / Q000737:chemistry*; D030562:Databases, Protein; D016571:Neural Networks, Computer; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012372:ROC Curve; D012680:Sensitivity and Specificity; D020539:Sequence Analysis, Protein / Q000379:methods*; D060388:Support Vector Machine
chemical_list: D000682:Amyloid; D010455:Peptides