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ProLuCID: An improved SEQUEST-like algorithm with enhanced sensitivity and specificity
Open accessAbstract
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.
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“Under serum-free survival conditions, we have previously observed that the cells do not proliferate, and thus we are measuring loss of viability in these cells under serum-free conditions with pharmacological treatment 49.”
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Yu, E. W. (2021) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736977845.793582677
Zhuang, Z., & Gui, W. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735998265.793563718
The C. elegans ASPP homolog APE-1 is a junctional protein phosphatase 1 modulatorPreprint
Beacham, G. M., Wei, D. T., Beyrent, E., Zhang, Y., Zheng, J., Camacho, M. M. K., Florens, L. A., & Hollopeter, G. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.02.15.480428
Cuervo, A. M., & Kaushik, S. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735813510.793562701
Stewart, M. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734041309.793552289
Cheng, L.-C., Zhang, X., Abhinav, K., Nguyen, J. A., Baboo, S., Martínez‐Bartolomé, S., Branon, T. C., Ting, A. Y., Loose, E., Yates, J. R., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.11.491529
“MS/MS spectra were searched using the ProLuCID algorithm (Xu et al., 2015) against a UniProt SwissProt Mus musculus reviewed proteome sequence database appended with the sequences of common contaminant proteins, and with the reverse sequences as decoy (UniProt, accessed 2018-11-28, total 34,189…”
MethodSelf-citationVitorino, F. N. D. L. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.87.2022.tde-29112022-085014
Multiplexed Quantitative Proteomics Analysis of Developing Human Brain Organoids
Florens, L. A., Saraf, A., Hao, Y., Zhang, Y., Wang, Y., Parmely, T. J., Zhao, C., & Washburn, M. P. (2023) · Neuromethods · doi:10.1007/978-1-0716-2875-1_22
Submitochondrial Protein Translocation in Thermogenic RegulationPreprint
Haczeyni, F., Jordan, J. M., Stein, B. D., Steensels, S., Li, L., Dartigue, V., Şarklıoğlu, S. S., Qiao, J., Zhou, X. K., Dannenberg, A. J., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.04.539294
“Because mitochondrial stress increases the acidity of the matrix 28,34–36 , we next investigated whether the translocation of these 73 proteins were rooted in pH-dependent interactions like SIRT3 and ATP synthase.”
InfluentialMcClatchy, D. B., & Yates, J. R. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.16.603801
Self-citationBomba-Warczak, E. K., Velez, K. M., Zhou, L. T., Guillermier, C., Edassery, S. L., Steinhauser, M. L., Savas, J. N., & Duncan, F. E. (2024) · eLife · doi:10.7554/elife.93172.2
Gamaleldin, M., Yu, N., Diedrich, J. K., Ma, Y., Wienand, A., McClatchy, D. B., Nykjær, A., Nabavi, S., & Yates, J. R. (2024) · Journal of Proteome Research · doi:10.1021/acs.jproteome.4c00180
Self-citationProximity based proteomics reveals Git1 as a regulator of Smoothened signalingPreprint
Zhang, J., Kaur, G., Cai, E., Gutierrez, O. T., Liu, X., Baboo, S., Diedrich, J. K., Zhu, J., Myers, B. R., Yates, J. R., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.06.631593
Self-citationLavallée‐Adam, M., Pelletier, A. R., Diedrich, J. K., Pinto, A. F. M., Martínez‐Bartolomé, S., Petrascheck, M., Moresco, J. J., & Yates, J. R. (2025) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.4c00269
Self-citationMa, R., Kang, M., Kim, G. H., Kang, H., Lee, S., Yang, Y., Lee, H. J., Choi, S., Kim, S., Kim, S., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.06.652352
Comparative Proteomic Analysis Reveals Altered Ciliary Proteins in Sickle Cell Disease
Mohieldin, A. M., Spencer, M., Bernal, C., Fadol, W. B., Gupta, A., Thirugnanam, K., Delahunty, C. M., Nunez, F., Pan, A. Y., Brandow, A. M., et al. (2025) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5c00168
Self-citationNitric oxide‐forming nitrite reductases in the anaerobic ammonium oxidizer Kuenenia stuttgartiensis
Vermeir, F. J., Nijman, L. W., Jansen, R. S., van Niftrik, L., & Versantvoort, W. (2025) · FEBS Open Bio · doi:10.1002/2211-5463.70086
“…real-time database searching of acquired MS/MS spectra against the provided custom K. stuttgartiensis protein sequence database using the following settings: ProLuCID database search algorithm [49], 20 p.p.m. precursor ion mass tolerance, 30 p.p.m. fragment ion mass tolerance, full tryptic…”
Advancements in computational tools in proteomics: Revolutionizing data analysis
Therachiyil, L., Anand, A., Ahmad, A., Korashy, H. M., & Uddin, S. (2025) · International review of cytology · doi:10.1016/bs.ircmb.2025.11.003
Proteomic and biochemical characterization of Bothrops pubescens (Serpentes: Viperidae) venom
Berasain, P., Pinto, A. F. M., Zelanis, A., Cúparo, M., Baletta, S., Carreira, S., Staats, C. C., Termignoni, C., Diedrich, J. K., Yates, J. R., et al. (2025) · Toxicon · doi:10.1016/j.toxicon.2025.108953
Self-citationda Silva Vaz Junior, I., Lu, S., Pinto, A. F. M., Diedrich, J. K., Yates, J. R., Mulenga, A., Termignoni, C., Ribeiro, J. M., & Tirloni, L. (2024) · Figshare · doi:10.6084/m9.figshare.26673600
Self-citationda Silva Vaz Junior, I., Lu, S., Pinto, A. F. M., Diedrich, J. K., Yates, J. R., Mulenga, A., Termignoni, C., Ribeiro, J. M., & Tirloni, L. (2024) · Figshare · doi:10.6084/m9.figshare.26673594
Self-citationda Silva Vaz Junior, I., Lu, S., Pinto, A. F. M., Diedrich, J. K., Yates, J. R., Mulenga, A., Termignoni, C., Ribeiro, J. M., & Tirloni, L. (2024) · Figshare · doi:10.6084/m9.figshare.26673606
Self-citationda Silva Vaz Junior, I., Lu, S., Pinto, A. F. M., Diedrich, J. K., Yates, J. R., Mulenga, A., Termignoni, C., Ribeiro, J. M., & Tirloni, L. (2024) · Figshare · doi:10.6084/m9.figshare.26673609
Self-citationda Silva Vaz Junior, I., Lu, S., Pinto, A. F. M., Diedrich, J. K., Yates, J. R., Mulenga, A., Termignoni, C., Ribeiro, J. M., & Tirloni, L. (2024) · Figshare · doi:10.6084/m9.figshare.26673597
Self-citationda Silva Vaz Junior, I., Lu, S., Pinto, A. F. M., Diedrich, J. K., Yates, J. R., Mulenga, A., Termignoni, C., Ribeiro, J. M., & Tirloni, L. (2024) · Figshare · doi:10.6084/m9.figshare.26673603
Self-citationda Silva Vaz Junior, I., Lu, S., Pinto, A. F. M., Diedrich, J. K., Yates, J. R., Mulenga, A., Termignoni, C., Ribeiro, J. M., & Tirloni, L. (2024) · Figshare · doi:10.6084/m9.figshare.26673582
Self-citationda Silva Vaz Junior, I., Lu, S., Pinto, A. F. M., Diedrich, J. K., Yates, J. R., Mulenga, A., Termignoni, C., Ribeiro, J. M., & Tirloni, L. (2024) · Figshare · doi:10.6084/m9.figshare.26673612
Self-citationda Silva Vaz Junior, I., Lu, S., Pinto, A. F. M., Diedrich, J. K., Yates, J. R., Mulenga, A., Termignoni, C., Ribeiro, J. M., & Tirloni, L. (2024) · Figshare · doi:10.6084/m9.figshare.26673579
Self-citation
Metadata
- Authors
- Xu, T., Park, S. K., Venable, J. D., Wohlschlegel, J. A., Diedrich, J. K., Cociorva, D., Lu, B., Liao, L., Hewel, J., Han, X., Wong, C. C. L., Fonslow, B., Delahunty, C., Gao, Y., Shah, H., & Yates, J. R.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Yates, J.R.
- ORCID
- Venue
- Journal of Proteomics
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 129
- Pages
- 16-24
- ISSN
- 1874-3919 (ISSN-L)
- PMC
- PMC4630125
- OpenAlex
- W2182963873
- Cited by
- 511
- References
- 51
- Citations by year
- 2026: 23 · 2025: 41 · 2024: 65 · 2023: 45 · 2022: 51 · 2021: 56 · 2020: 56 · 2019: 60 · 2018: 43 · 2017: 46 · 2016: 22 · 2015: 3
- FWCI
- 16.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Proteomics (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- NIH (5U01 DE016267-04, 5R01 HL079442-04, R01 MH067880, P41 GM103533)
- NHLBI (HHSN268201000035C)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- peptide identification, tandem mass spectrometry, SEQUEST, Z-score
- MeSH terms
- Algorithms, Amino Acid Sequence, Molecular Sequence Data, Pattern Recognition, Automated, Peptide Mapping, Proteins, Sensitivity and Specificity, Software, Reproducibility of Results, Sequence Analysis, Protein, Databases, Protein, Tandem Mass Spectrometry, Data Mining
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