title: ProLuCID: An improved SEQUEST-like algorithm with enhanced sensitivity and specificity.
abstract: ProLuCID, a new algorithm for peptide identification using tandem mass spectrometry and protein sequence databases has been developed. This algorithm uses a three tier scoring scheme. First, a binomial probability is used as a preliminary scoring scheme to select candidate peptides. The binomial probability scores generated by ProLuCID minimize molecular weight bias and are independent of database size. A modified cross-correlation score is calculated for each candidate peptide identified by the binomial probability. This cross-correlation scoring function models the isotopic distributions of fragment ions of candidate peptides which ultimately results in higher sensitivity and specificity than that obtained with the SEQUEST XCorr. Finally, ProLuCID uses the distribution of XCorr values for all of the selected candidate peptides to compute a Z score for the peptide hit with the highest XCorr. The ProLuCID Z score combines the discriminative power of XCorr and DeltaCN, the standard parameters for assessing the quality of the peptide identification using SEQUEST, and displays significant improvement in specificity over ProLuCID XCorr alone. ProLuCID is also able to take advantage of high resolution MS/MS spectra leading to further improvements in specificity when compared to low resolution tandem MS data. A comparison of filtered data searched with SEQUEST and ProLuCID using the same false discovery rate as estimated by a target-decoy database strategy, shows that ProLuCID was able to identify as many as 25% more proteins than SEQUEST. ProLuCID is implemented in Java and can be easily installed on a single computer or a computer cluster. This article is part of a Special Issue entitled: Computational Proteomics.
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA; Dow AgroSciences LLC, Indianapolis, IN 46268, USA.
authors.forename: T
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Venable
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Wohlschlegel
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Diedrich
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: D
authors.initials: D
authors.lastname: Cociorva
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: B
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: L
authors.initials: L
authors.lastname: Liao
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: J
authors.initials: J
authors.lastname: Hewel
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: X
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: C C L
authors.initials: CCL
authors.lastname: Wong
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: B
authors.initials: B
authors.lastname: Fonslow
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: C
authors.initials: C
authors.lastname: Delahunty
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA.
authors.forename: H
authors.initials: H
authors.lastname: Shah
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR11, La Jolla, CA 92037, USA. Electronic address: jyates@scripps.edu.
authors.forename: J R
authors.initials: JR
authors.lastname: Yates
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D057225:Data Mining / Q000379:methods; D030562:Databases, Protein; D008969:Molecular Sequence Data; D010363:Pattern Recognition, Automated / Q000379:methods; D010449:Peptide Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D011506:Proteins
keywords: Bioinformatics; Identification; Mass spectrometry; ProLuCID; Proteomics; Sequest