title: Complete De Novo Assembly of Monoclonal Antibody Sequences.
abstract: De novo protein sequencing is one of the key problems in mass spectrometry-based proteomics, especially for novel proteins such as monoclonal antibodies for which genome information is often limited or not available. However, due to limitations in peptides fragmentation and coverage, as well as ambiguities in spectra interpretation, complete de novo assembly of unknown protein sequences still remains challenging. To address this problem, we propose an integrated system, ALPS, which for the first time can automatically assemble full-length monoclonal antibody sequences. Our system integrates de novo sequencing peptides, their quality scores and error-correction information from databases into a weighted de Bruijn graph to assemble protein sequences. We evaluated ALPS performance on two antibody data sets, each including a heavy chain and a light chain. The results show that ALPS was able to assemble three complete monoclonal antibody sequences of length 216-441 AA, at 100% coverage, and 96.64-100% accuracy.
authors: David R. Cheriton School of Computer Science, University of Waterloo, Waterloo, Ontario, Canada.
authors: Ngoc Hieu
authors: NH
authors: Tran
authors: David R. Cheriton School of Computer Science, University of Waterloo, Waterloo, Ontario, Canada.|Bioinformatics Solutions Inc., Waterloo, Ontario, Canada.
authors: M Ziaur
authors: MZ
authors: Rahman
authors: Bioinformatics Solutions Inc., Waterloo, Ontario, Canada.
authors: Lin
authors: L
authors: He
authors: Bioinformatics Solutions Inc., Waterloo, Ontario, Canada.
authors: Lei
authors: L
authors: Xin
authors: Bioinformatics Solutions Inc., Waterloo, Ontario, Canada.
authors: Baozhen
authors: B
authors: Shan
authors: David R. Cheriton School of Computer Science, University of Waterloo, Waterloo, Ontario, Canada.
authors: Ming
authors: M
authors: Li
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001331:Automation; D002645:Chickens; D002853:Chromatography, Liquid; D002918:Chymotrypsin / Q000737:chemistry; D019295:Computational Biology; D020451:Contig Mapping; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008666:Metalloendopeptidases / Q000737:chemistry; D009113:Muramidase; D010455:Peptides / Q000737:chemistry; D015203:Reproducibility of Results; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D053719:Tandem Mass Spectrometry; D014357:Trypsin / Q000737:chemistry
chemical_list: D000596:Amino Acids; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D010455:Peptides; D009113:Muramidase; D002918:Chymotrypsin; D014357:Trypsin; D008666:Metalloendopeptidases; C058921:endoproteinase Asp-N