Comparison of False Discovery Rate Control Strategies for Variant Peptide Identifications in Shotgun Proteogenomics.
Proteogenomic studies aiming at identification of variant peptides using customized database searches of mass spectrometry data are facing a dilemma of selecting the most efficient database search strategy: A choice has to be made between using combined or sequential searches against reference (wild-type) and mutant protein databases or directly against the mutant database without the wild-type one. Here we called these approaches "all-together", "one-by-one", and "direct", respectively. We share the results of the comparison of these search strategies obtained for large data sets of publicly available proteogenomic data. On the basis of the results of this evaluation, we found that the "all-together" strategy provided, in general, more variant peptide identifications compared with the "one-by-one" approach, while showing similar performance for some specific cases. To validate further the results of this study, we performed a control comparison of the strategies in question using publicly available data for a mixture of the annotated human protein standard UPS1 and E. coli. For these data, both "all-together" and "one-by-one" approaches showed similar sensitivity and specificity of the searches, while the "direct" approach resulted in an increased number of false identifications.
Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences , Moscow 119334, Russia.|Moscow Institute of Physics and Technology (State University) , Moscow Region, Dolgoprudny 141700, Russia.
Mark V
MV
Ivanov
Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences , Moscow 119334, Russia.|Moscow Institute of Physics and Technology (State University) , Moscow Region, Dolgoprudny 141700, Russia.
Anna A
AA
Lobas
Institute of Biomedical Chemistry , Moscow 119121, Russia.|Engelhardt Institute of Molecular Biology, Russian Academy of Sciences , Moscow 119991, Russia.
Dmitry S
DS
Karpov
Institute of Biomedical Chemistry , Moscow 119121, Russia.|Pirogov Russian National Research Medical University , Moscow 117997, Russia.
Sergei A
SA
Moshkovskii
Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences , Moscow 119334, Russia.|Moscow Institute of Physics and Technology (State University) , Moscow Region, Dolgoprudny 141700, Russia.
Mikhail V
0000-0001-9572-3452
MV
Gorshkov
D016208:Databases, Factual; D030562:Databases, Protein; D029968:Escherichia coli Proteins; D006801:Humans; D013058:Mass Spectrometry; D050505:Mutant Proteins; D010455:Peptides / Q000235:genetics; D000071696:Proteogenomics / Q000379:methods* / Q000592:standards; D012680:Sensitivity and Specificity
D029968:Escherichia coli Proteins; D050505:Mutant Proteins; D010455:Peptides
cancer proteome; false discovery rate; proteogenomics; shotgun proteomics; variant peptides