Prediction and Analysis of Antibody Amyloidogenesis from Sequences

Chyn Liaw, Chun Wei Tung, Shinn Ying Ho

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Antibody amyloidogenesis is the aggregation of soluble proteins into amyloid fibrils that is one of major causes of the failures of humanized antibodies. The prediction and prevention of antibody amyloidogenesis are helpful for restoring and enhancing therapeutic effects. Due to a large number of possible germlines, the existing method is not practical to predict sequences of novel germlines, which establishes individual models for each known germline. This study proposes a first automatic and across-germline prediction method (named AbAmyloid) capable of predicting antibody amyloidogenesis from sequences. Since the amyloidogenesis is determined by a whole sequence of an antibody rather than germline-dependent properties such as mutated residues, this study assess three types of germline-independent sequence features (amino acid composition, dipeptide composition and physicochemical properties). AbAmyloid using a Random Forests classifier with dipeptide composition performs well on a data set of 12 germlines. The within- and across-germline prediction accuracies are 83.10% and 83.33% using Jackknife tests, respectively, and the novel-germline prediction accuracy using a leave-one-germline-out test is 72.22%. A thorough analysis of sequence features is conducted to identify informative properties for further providing insights to antibody amyloidogenesis. Some identified informative physicochemical properties are amphiphilicity, hydrophobicity, reverse turn, helical structure, isoelectric point, net charge, mutability, coil, turn, linker, nuclear protein, etc. Additionally, the numbers of ubiquitylation sites in amyloidogenic and non-amyloidogenic antibodies are found to be significantly different. It reveals that antibodies less likely to be ubiquitylated tend to be amyloidogenic. The method AbAmyloid capable of automatically predicting antibody amyloidogenesis of novel germlines is implemented as a publicly available web server at http://iclab.life.nctu.edu.tw/abamyloid.

Original languageEnglish
Article numbere53235
JournalPLoS One
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 15 2013
Externally publishedYes

Fingerprint

germ cells
antibodies
prediction
Antibodies
Dipeptides
dipeptides
Chemical analysis
Antibodies, Monoclonal, Humanized
physicochemical properties
Ubiquitination
Isoelectric Point
Therapeutic Uses
Hydrophobicity
Nuclear Proteins
Hydrophobic and Hydrophilic Interactions
Amyloid
Sequence Analysis
Amino Acid Sequence
nuclear proteins
Classifiers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Prediction and Analysis of Antibody Amyloidogenesis from Sequences. / Liaw, Chyn; Tung, Chun Wei; Ho, Shinn Ying.

In: PLoS One, Vol. 8, No. 1, e53235, 15.01.2013.

Research output: Contribution to journalArticle

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