Zuo-Fei YUAN, Ph.D.

 

Email:    zuoyuan@pennmedicine.upenn.edu

Phone:    215-582-5288

Address:  1326 S Markoe ST, Philadelphia, PA 19143

 

RESEARCH INTERESTS

Computational proteomics, protein identification and quantification, histones, preprocessing for MS and MS/MS, peptide scoring and validation, data analysis and pipeline designing, modification discovery, spectral library search, de novo, proteogenomics search, genome analysis.

 

EDUCATION

Institute of Computing Technology, Chinese Academy of Sciences, July 2012

Ph.D. in Computer Science

 

Central South University, China, July 2004

B.S. in Computer Science

 

RESEARCH EXPERIENCE

Research Associate

Perelman School of Medicine, University of Pennsylvania

Children's Hospital of Philadelphia

 

Quantitative analysis of proteomics and genomics data, and integration of RNA-Seq and proteomic datasets

November 2017 - Present

           Complete the computational platform for processing Epi-Proteomics mass spectrometry data; develop the pipeline to quantify isobaric phosphopeptides; develop the workflow to combine multiomics data to demonstrate the relationship of system biology.

           Histone profiling of leukemia samples; proteomics profiling of leukemia samples; RNA-Seq and ChIP-Seq analysis of leukemia samples; proteogenomics research for patient samples.

 

Postdoctoral Researcher

Perelman School of Medicine, University of Pennsylvania

 

Characterizing and quantifying histone and protein modifications

November 2012 C October 2017

           Developed an accurate computational approach to quantify histone modifications, obtained the layouts (i.e. the time relationship) of histone modifications, and discriminated isobaric peptides with modifications due to their time overlapping.

           Developed lots of data analysis workflows: histone peptide identification, modifications site localization, open database searching, and SILAC and TMT labeling and label-free quantification.

 

Ph.D. Student

Institute of Computing Technology, Chinese Academy of Sciences

 

Accurate Determination of Monoisotopic Peaks in High-resolution Mass Spectra

September 2008 - July 2012

           Developed an effective approach to judge overlapping isotopic clusters, designed a new scoring function to identify co-eluted peptides, and proposed a universal approach to validate methods for monoisotopic peak determination.

           Implemented our method with Python in three weeks, published a paper on Proteomics, wrote a review, and filed a patent.

           Contributed to the study of iPRG 2010 for phosphopeptides and the identification of core fucosylated glycoproteins.

 

In-depth Analysis of Massive Spectral Data

November 2007 - July 2012

           Initiated an analysis pipeline that includes preprocessing, modification discovery, parameter determination by pre-search, the second database search and filtering, spectral library search, proteogenomics search, sample comparison, and cloud computing.

           Validated search results based on the target-decoy approach and SVM for multiple search engines, e.g., pFind, Mascot and SEQUEST.

           Contributed to the study of iPRG 2008 for iTRAQ spectra, the study of iPRG 2011 for ETD spectra, and the 18O labeling quantification of core fucosylated glycoproteins.

 

Initiating the Application of pFind at the Institute of Zoology, Chinese Academy of Sciences

September 2009 - July 2012

           Provided technique support and software training for a biological engineer.

           Distributed the feedback to the tool authors, and obtained some new findings.

           Made pFind as a fast, convenient, and functional identification studio outside our group for the first time.

 

PUBLICATIONS (with >800 citations)

27. Tan, L.; Ke, Z.; Tombline, G.; Macoretta, N.; Hayes, K.; Tian, X.; Lv, R.; Ablaeva, J.; Gilbert, M.; Bhanu, N. V.; Yuan, Z. F.; Garcia, B. A.; Shi, Y. G.; Shi, Y.; Seluanov, A.; Gorbunova, V., Naked Mole Rat Cells Have a Stable Epigenome that Resists iPSC Reprogramming. Stem Cell Reports 2017, 9, (5), 1721-1734.

 

26. Simithy, J.; Sidoli, S.; Yuan, Z. F.; Coradin, M.; Bhanu, N. V.; Marchione, D. M.; Klein, B. J.; Bazilevsky, G. A.; McCullough, C. E.; Magin, R. S.; Kutateladze, T. G.; Snyder, N. W.; Marmorstein, R.; Garcia, B. A., Characterization of scarcely explored histone acylations links chromatin modifications with metabolism. Nature Communications 2017, 8, 1141.

 

25. Kori, Y.; Sidoli, S.; Yuan, Z. F.; Lund, P. J.; Zhao, X.; Garcia, B. A., Proteome-wide acetylation dynamics in human cells. Scientific Reports 2017, 7, (1), 10296.

 

24. Lu, C. C.; Tian, S. S.; Zhai, G. J.; Yuan, Z. F.; Li, Y. J.; He, X. W.; Zhang, Y. K.; Zhang, K., Probing the Binding Interfaces of Histone-Aptamer by Photo Cross-Linking Mass Spectrometry. Acs Chemical Biology 2017, 12, (1), 57-62.

 

23. Lin, S.; Yuan, Z. F.; Han, Y. M.; Marchione, D. M.; Garcia, B. A., Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells. Journal of Biological Chemistry 2016, 291, (29), 15342-15357.

 

22. Wang, X. S.; Yuan, Z. F.; Fan, J.; Karch, K. R.; Ball, L. E.; Denu, J. M.; Garcia, B. A., A Novel Quantitative Mass Spectrometry Platform for Determining Protein O-GlcNAcylation Dynamics. Molecular & Cellular Proteomics 2016, 15, (7), 2462-2475.

 

21. Han, Y. M.; Yuan, Z. F.; Molden, R. C.; Garcia, B. A., Monitoring Cellular Phosphorylation Signaling Pathways into Chromatin and Down to the Gene Level. Molecular & Cellular Proteomics 2016, 15, (3), 834-853.

 

20. Hu, J. L.; Donahue, G.; Dorsey, J.; Govin, J.; Yuan, Z. F.; Garcia, B. A.; Shah, P. P.; Berger, S. L., H4K44 Acetylation Facilitates Chromatin Accessibility during Meiosis. Cell Reports 2015, 13, (9), 1772-1780.

 

19. Moraes, I.; Yuan, Z. F.; Liu, S. C.; Souza, G. M.; Garcia, B. A.; Casas-Mollano, J. A., Analysis of Histones H3 and H4 Reveals Novel and Conserved Post-Translational Modifications in Sugarcane. PLoS One 2015, 10, (7), 25.

 

18. Maze, I.; Wenderski, W.; Noh, K. M.; Bagot, R. C.; Tzavaras, N.; Purushothaman, I.; Elsasser, S. J.; Guo, Y.; Ionete, C.; Hurd, Y. L.; Tamminga, C. A.; Halene, T.; Farrelly, L.; Soshnev, A. A.; Wen, D. C.; Rafii, S.; Birtwistle, M. R.; Akbarian, S.; Buchholz, B. A.; Blitzer, R. D.; Nestler, E. J.; Yuan, Z. F.; Garcia, B. A.; Shen, L.; Molina, H.; Allis, C. D., Critical Role of Histone Turnover in Neuronal Transcription and Plasticity. Neuron 2015, 87, (1), 77-94.

 

17. Chi, H.; He, K.; Yang, B.; Chen, Z.; Sun, R. X.; Fan, S. B.; Zhang, K.; Liu, C.; Yuan, Z. F.; Wang, Q. H.; Liu, S. Q.; Dong, M. Q.; He, S. M., pFind-Alioth: A novel unrestricted database search algorithm to improve the interpretation of high-resolution MS/MS data. Journal of Proteomics 2015, 125, 89-97.

 

16. Yuan, Z. F.; Lin, S.; Molden, R. C.; Cao, X. J.; Bhanu, N. V.; Wang, X. S.; Sidoli, S.; Liu, S. C.; Garcia, B. A., EpiProfile Quantifies Histone Peptides With Modifications by Extracting Retention Time and Intensity in High-resolution Mass Spectra. Molecular & Cellular Proteomics 2015, 14, (6), 1696-1707.

 

15. Sidoli, S.; Yuan, Z. F.; Lin, S.; Karch, K.; Wang, X. S.; Bhanu, N.; Arnaudo, A. M.; Britton, L. M.; Cao, X. J.; Gonzales-Cope, M.; Han, Y. M.; Liu, S. C.; Molden, R. C.; Wein, S.; Afjehi-Sadat, L.; Garcia, B. A., Drawbacks in the use of unconventional hydrophobic anhydrides for histone derivatization in bottom-up proteomics PTM analysis. Proteomics 2015, 15, (9), 1459-1469.

 

14. Beck, D. B.; Narendra, V.; Drury, W. J.; Casey, R.; Jansen, P.; Yuan, Z. F.; Garcia, B. A.; Vermeulen, M.; Bonasio, R., In Vivo Proximity Labeling for the Detection of Protein-Protein and Protein-RNA Interactions. Journal of Proteome Research 2014, 13, (12), 6135-6143.

 

13. Yuan, Z. F.; Lin, S.; Molden, R. C.; Garcia, B. A., Evaluation of Proteomic Search Engines for the Analysis of Histone Modifications. Journal of Proteome Research 2014, 13, (10), 4470-4478.

 

12. Lin, S.; Wein, S.; Gonzales-Cope, M.; Otte, G. L.; Yuan, Z. F.; Afjehi-Sadat, L.; Maile, T.; Berger, S. L.; Rush, J.; Lill, J. R.; Arnott, D.; Garcia, B. A., Stable-isotope-labeled Histone Peptide Library for Histone Post-translational Modification and Variant Quantification by Mass Spectrometry. Molecular & Cellular Proteomics 2014, 13, (9), 2450-2466.

 

11. Lee, J. V.; Carrer, A.; Shah, S.; Snyder, N. W.; Wei, S. Z.; Venneti, S.; Worth, A. J.; Yuan, Z. F.; Lim, H. W.; Liu, S. C.; Jackson, E.; Aiello, N. M.; Haas, N. B.; Rebbeck, T. R.; Judkins, A.; Won, K. J.; Chodosh, L. A.; Garcia, B. A.; Stanger, B. Z.; Feldman, M. D.; Blair, I. A.; Wellen, K. E., Akt-Dependent Metabolic Reprogramming Regulates Tumor Cell Histone Acetylation. Cell Metabolism 2014, 20, (2), 306-319.

 

10. Liu, C.; Song, C. Q.; Yuan, Z. F.; Fu, Y.; Chi, H.; Wang, L. H.; Fan, S. B.; Zhang, K.; Zeng, W. F.; He, S. M.; Dong, M. Q.; Sun, R. X., pQuant Improves Quantitation by Keeping out Interfering Signals and Evaluating the Accuracy of Calculated Ratios. Analytical Chemistry 2014, 86, (11), 5286-5294.

 

9. Yuan, Z. F.; Arnaudo, A. M.; Garcia, B. A., Mass Spectrometric Analysis of Histone Proteoforms. Annual Review of Analytical Chemistry 2014; Vol. 7, pp 113-128.

 

8. Yuan, Z. F.; Liu, C.; Wang, H. P.; Sun, R. X.; Fu, Y.; Zhang, J. F.; Wang, L. H.; Chi, H.; Li, Y.; Xiu, L. Y.; Wang, W. P.; He, S. M., pParse: A method for accurate determination of monoisotopic peaks in high-resolution mass spectra. Proteomics 2012, 12, (2), 226-235.

 

7. Ye, D.; Fu, Y.; Sun, R. X.; Wang, H. P.; Yuan, Z. F.; Chi, H.; He, S. M., Open MS/MS spectral library search to identify unanticipated post-translational modifications and increase spectral identification rate. Bioinformatics 2010, 26, (12), i399-i406.

 

6. Wang, L. H.; Wang, W. P.; Chi, H.; Wu, Y. J.; Li, Y.; Fu, Y.; Zhou, C.; Sun, R. X.; Wang, H. P.; Liu, C.; Yuan, Z. F.; Xiu, L. Y.; He, S. M., An efficient parallelization of phosphorylated peptide and protein identification. Rapid Communications in Mass Spectrometry 2010, 24, (12), 1791-1798.

 

5. Chi, H.; Sun, R. X.; Yang, B.; Song, C. Q.; Wang, L. H.; Liu, C.; Fu, Y.; Yuan, Z. F.; Wang, H. P.; He, S. M.; Dong, M. Q., pNovo: De novo Peptide Sequencing and Identification Using HCD Spectra. Journal of Proteome Research 2010, 9, (5), 2713-2724.

 

4. Li, Y.; Chi, H.; Wang, L. H.; Wang, H. P.; Fu, Y.; Yuan, Z. F.; Li, S. J.; Liu, Y. S.; Sun, R. X.; Zeng, R.; He, S. M., Speeding up tandem mass spectrometry based database searching by peptide and spectrum indexing. Rapid Communications in Mass Spectrometry 2010, 24, (6), 807-814.

 

3. Jia, W.; Lu, Z.; Fu, Y.; Wang, H. P.; Wang, L. H.; Chi, H.; Yuan, Z. F.; Zheng, Z. B.; Song, L. N.; Han, H. H.; Liang, Y. M.; Wang, J. L.; Cai, Y.; Zhang, Y. K.; Deng, Y. L.; Ying, W. T.; He, S. M.; Qian, X. H., A Strategy for Precise and Large Scale Identification of Core Fucosylated Glycoproteins. Molecular & Cellular Proteomics 2009, 8, (5), 913-923.

 

2. Fu, Y.; Jia, W.; Lu, Z.; Wang, H. P.; Yuan, Z. F.; Chi, H.; Li, Y.; Xiu, L. Y.; Wang, W. P.; Liu, C.; Wang, L. H.; Sun, R. X.; Gao, W.; Qian, X. H.; He, S. M., Efficient discovery of abundant post-translational modifications and spectral pairs using peptide mass and retention time differences. Bmc Bioinformatics 2009, 10, 12.

 

1. Wang, L. H.; Li, D. Q.; Fu, Y.; Wang, H. P.; Zhang, J. F.; Yuan, Z. F.; Sun, R. X.; Zeng, R.; He, S. M.; Gao, W., pFind 2.0: a software package for peptide and protein identification via tandem mass spectrometry. Rapid Communications in Mass Spectrometry 2007, 21, (18), 2985-2991.

 

CONFERENCE Papers

5. Yuan, Z. F.; Sidoli, S.; Fujiwara, R.; Kulej, K.; Garcia, B. A., Discriminating isobaric phosphopeptides using data-independent acquisition mass spectrometry. 65th American Society for Mass Spectrometry (ASMS) 2017 (Poster).

 

4. Yuan, Z. F.; Sidoli, S.; Lin, S.; Wang, X. S.; Bhanu, N. V.; Garcia, B. A., Decoding histone post-translational modifications by bottom-up mass spectrometry. 64th American Society for Mass Spectrometry (ASMS) 2016 (Poster).

 

3. Yuan, Z. F.; Sidoli, S.; Lin, S.; Wang, X. S.; Bhanu, N. V.; Garcia, B. A., Decoding histone post-translational modifications by bottom-up mass spectrometry. 12th United States Human Proteome Organization (US HUPO) 2016 (Poster).

 

2. Yuan, Z. F.; Lin, S.; Molden, R. C.; Cao, X. J.; Bhanu, N. V.; Wang, X. S.; Sidoli, S.; Liu, S. C.; Garcia, B. A., Quantification of histone post-translational modifications by mass spectrometry. 63th American Society for Mass Spectrometry (ASMS) 2015 (Poster).

 

1. Yuan, Z. F.; Lin, S.; Garcia, B. A., Evaluation of accessible database searching engines for accurate identification of histone post-translational modifications. 62th American Society for Mass Spectrometry (ASMS) 2014 (Poster).

 

ADDITIONAL PROFESSIONAL EXPERIENCE

The Third MaxQuant Summer School in Max Planck Institute of Biochemistry

Munich, Germany, May 2011

           Learned the forefront techniques in computational proteomics, consulted with tutors about peptide identification, and communicated with participants about their research work.

 

The First China Workshop on Computational Proteomics

Beijing, China, November 2010

           Designed the workshop program, trained 61 participants from China and USA on database search, and organized participants for registration, meals, and the workshop.

           Communicated with participants about computational proteomics, and collaborated with experts.

 

Preprocessing Tandem Mass Spectra for Better Peptide Identification

April - October 2006

           Implemented the Gaussian Mixture Model in C/C++ to find the baseline in a spectrum.

           Integrated the preprocessing algorithm into a pipeline toolbox, and designed an automatic testing strategy to test the preprocessing algorithm.

           Supported the publication on RCM by providing materials, such as webpage and test cases.

 

AWARDS

Excellent Student Award by the institute director, ICT, CAS, 2011

Excellent Student Award of Joint Research & Development Laboratory, ICT, CAS, 2010

Excellent Student Award of Advanced Computing Research Laboratory, ICT, CAS, 2009

Excellent Student Award of Advanced Computing Research Laboratory, ICT, CAS, 2007

Second Prize of Outstanding Undergraduate Thesis, Central South University, 2004

National Scholarship Award, Central South University, 2002