Priscilla Yeung

All Publications

• Detection of monoclonal alpha heavy chains in the absence of other monoclonal proteins in a patient with a history of IgG-κ MGUS. Clinica chimica acta; international journal of clinical chemistry Mann, M. W., Yeung, P. S., Luo, R. Y., Lynch, K. L., Wu, A. H., Lusk, H. J. 2025; 579: 120636

  View details for DOI 10.1016/j.cca.2025.120636

  View details for PubMedID 41062053

• Post-Translationally Modified Proteoforms as Biomarkers: From Discovery to Clinical Use. Clinical chemistry Luo, R. Y., Yeung, P. S., Mann, M. W., Zhang, L., Yang, Y. K., Hoofnagle, A. N. 2025

  Abstract

  Protein biomarkers are routinely measured for disease diagnosis and prognosis in clinical laboratories. Since most assays focus on protein quantity, information about proteoforms is often not acquired. Proteoforms of a protein represent the complex integration of genetic polymorphism, alternative splicing of RNA transcripts, and post-translational modifications (PTMs) on the amino-acid backbone. A detailed analysis of the post-translationally modified proteoforms (PTMPs), which are influenced by pathophysiological conditions, may lead to more precise diagnosis and prognosis.This article first discusses the methodologies used to accurately detect and characterize PTMPs, i.e., immunoassays, electrophoresis, chromatography, and intact and proteolysis-aided mass spectrometry techniques. Then it reviews specific examples of PTMP biomarkers that have been successfully translated from biomarker discovery to clinical use. The examples include β2-transferrin for cerebrospinal fluid leak diagnosis, phosphorylated tau proteoforms for Alzheimer disease diagnosis, and fucosylated alpha-fetoprotein for hepatocellular carcinoma prognosis. In addition, the article provides prospective views of novel analytical technologies and promising new PTMP biomarkers entering clinical practice.In summary, PTMs are controlled by biochemical processes to modulate the functions of proteins by expanding their chemical diversity. PTM alterations in proteins can be indicators for pathophysiological conditions. Advances in analytical technologies are deepening our understanding of PTMPs and paving the way for their translation to clinical use. As research continues to discover the clinical meaning of PTMP biomarkers, they are poised to become valuable additions to the clinical testing menu for precision medicine.

  View details for DOI 10.1093/clinchem/hvaf094

  View details for PubMedID 40850932

• Application of capillary electrophoresis-high-resolution mass spectrometry to diagnose 2 rare hemoglobin variants in the San Francisco Bay area. Laboratory medicine Lu, C., Wong, C. V., Yeung, P. S., Luo, R. Y. 2025

  Abstract

  Hemoglobin (Hb) variants are genetic disorders that lead to structural impairment of Hb. Most of these disorders lack clinical symptoms and are typically detected through prenatal, newborn, or routine health screenings. Hemoglobinopathy evaluation typically starts with screening tests performed by electrophoresis or liquid chromatography. In some cases, on top of the conventional test results, racial or geographic information is incorporated to assess high-risk populations for certain mutations, but this addition can also at times be misleading.This report presents 2 rare cases of Hb variants in the San Francisco Bay area that were diagnosed using the capillary electrophoresis-high-resolution mass spectrometry (CE-HR-MS) method: Hb New York trait in case 1 and Hb Al-Ain Abu Dhabi trait in case 2.Overall, these results demonstrate the utility of CE-HR-MS as an updated approach to definitively diagnose hemoglobin variants.CE-HR-MS has the potential to be implemented into clinical practice as an alternative diagnostic method to gene sequencing.

  View details for DOI 10.1093/labmed/lmaf029

  View details for PubMedID 40560057

• High-resolution mass spectrometry measurement of N-terminal carbamylated hemoglobin as a potential marker for chronic diseases with elevated blood urea levels. Journal of mass spectrometry and advances in the clinical lab Chen, F., Yeung, P. S., Wong, C. V., Luo, R. Y. 2025; 35: 8-13

  Abstract

  N-terminal carbamylated hemoglobin (CarHb) reflects long-term blood urea levels and has potential as a marker for chronic kidney disease (CKD) and other chronic conditions with elevated blood urea levels. A liquid chromatography-high-resolution mass spectrometry (LC-HR-MS) method was developed to measure CarHb.Apparent CarHb/Hb ratios were calculated from the peak area ratios of carbamylated to native N-terminal peptides digested from hemoglobin alpha and beta subunits. Blood samples from healthy individuals, CKD patients, and chronic obstructive pulmonary disease (COPD) patients were analyzed.The apparent CarHb/Hb ratios were significantly higher in CKD and COPD patients compared to healthy individuals. However, no significant differences were observed between the CKD and COPD patient groups.In this study, an LC-HR-MS method was developed for quantifying the apparent CarHb/Hb ratios and exploring their potential for clinical diagnostic applications. CarHb is a promising marker for monitoring kidney diseases and other chronic conditions with elevated blood urea levels. Beyond CarHb, the use of other carbamylated proteins as clinical diagnostic and prognostic markers can be explored.

  View details for DOI 10.1016/j.jmsacl.2025.01.001

  View details for PubMedID 40034798

  View details for PubMedCentralID PMC11873320

• Clonality Determination by Detecting Unmodified Monoclonal Serum Free Light Chains Using On-Probe Extraction Coupled with Liquid Chromatography-High-Resolution Mass Spectrometry. Clinical chemistry Yeung, P. S., Liu, Y., Yang, S., Ruan, A., Kerr, C. R., Wong, C. V., Shi, R. Z., Iberri, D. J., Luo, R. Y. 2024

  Abstract

  Serum free light chains (FLCs) are an essential clinical biomarker for the diagnosis and monitoring of patients with plasma cell neoplasms. The current widely used immunoassay methods quantify total serum FLCs, which include monoclonal FLCs as well as FLCs in the polyclonal background. Patients with chronic diseases, inflammatory disorders, or renal dysfunction can have elevated total FLCs that lead to ambiguous results. These patients may benefit from a direct measurement of monoclonal FLCs. The purpose of this study was to develop a method that couples on-probe extraction (OPEX) with liquid chromatography-high-resolution mass spectrometry (LC-HR-MS), abbreviated to OPEX-MS, to directly determine the clonality of FLCs.OPEX immunocapture was performed using microprobes loaded with anti-kappa or anti-lambda light chain antibodies. Captured proteins were separated by reversed-phase LC and analyzed by HR-MS.Four cohorts of samples from unique patients were tested based on immunoassay FLC results. The LC-HR-MS analysis in the OPEX-MS method provides both a unique retention time along with deconvoluted masses of FLC monomers and dimers for each clone. The study found that 16 out of 49 (33%) kappa FLC elevated samples as well as 83 out of 100 (83%) dual kappa and lambda FLC elevated samples did not have monoclonal FLCs, which is consistent with the knowledge that there is often no clonal population in samples with mildly elevated FLC immunoassay results.The OPEX-MS method can serve as a complementary approach to directly determine clonality in patients with difficult-to-interpret FLC immunoassay results.

  View details for DOI 10.1093/clinchem/hvae130

  View details for PubMedID 39378225

• An up-conversion fluorescence lateral-flow immunoassay for rapid detection of Daratumumab in serum protein electrophoresis clinical samples. Clinica chimica acta; international journal of clinical chemistry Liu, Y., Tao, Y., Yeung, P. S., Lu, M., Liu, J., Yu, F., Shi, R., Yiqi Luo, R. 2024: 119677

  Abstract

  BACKGROUND: Daratumumab (DARA) is a commonly used monoclonal antibody (mAb) drug for the treatment of multiple myeloma (MM). Its appearance as a visible abnormal band in the gamma-region of a serum protein electrophoresis (SPEP) gel may interfere with the SPEP result interpretation. With the advantages of portability and rapid testing capabilities, up-conversion fluorescence lateral-flow immunoassay (LFA) can be an ideal solution to detect DARA interference.METHODS: An up-conversion fluorescence LFA strip was designed and constructed to perform semi-quantitative DARA testing in clinical samples. The LFA strip test was evaluated for limit of detection (LOD), dynamic range, and analytical interference.RESULTS: To demonstrate the clinical utility of the LFA strip, 43 SPEP-positive patient serum samples were tested for the presence of DARA, and the results exactly matched the DARA usage history in patient medical records.CONCLUSIONS: The performance of the up-conversion fluorescence LFA strip meets the purpose of clarifying DARA interference in SPEP results. It may be used as an independent and objective confirmation of the presence of DARA in clinical samples. The LFA strip offers a cost-effective rapid on-site test to check for DARA interference alongside standard SPEP equipment, which significantly improves the interpretation of ambiguous SPEP results involving DARA, and does not intervene the current SPEP workflow in clinical laboratory practice.

  View details for DOI 10.1016/j.cca.2024.119677

  View details for PubMedID 38636694

• Transport of Full-Length Proteins through a Nanopore: One Step Closer to Single-Molecule Proteomics. Clinical chemistry Yeung, P. S., Luo, R. Y. 2024; 70 (2): 462-463

  View details for DOI 10.1093/clinchem/hvad201

  View details for PubMedID 38321876

• Study of β1-transferrin and β2-transferrin using microprobe-capture in-emitter elution and high-resolution mass spectrometry. Scientific reports Luo, R. Y., Pfaffroth, C., Yang, S., Hoang, K., Yeung, P. S., Zehnder, J. L., Shi, R. Z. 2023; 13 (1): 14974

  Abstract

  Cerebrospinal fluid (CSF) leak can be diagnosed in clinical laboratories by detecting a diagnostic marker β2-transferrin (β2-Tf) in secretion samples. β2-Tf and the typical transferrin (Tf) proteoform in serum, β1-transferrin (β1-Tf), are Tf glycoforms. An innovative affinity capture technique for sample preparation, called microprobe-capture in-emitter elution (MPIE), was incorporated with high-resolution mass spectrometry (HR-MS) to study the Tf glycoforms and the primary structures of β1-Tf and β2-Tf. To implement MPIE, an analyte is first captured on the surface of a microprobe, and subsequently eluted from the microprobe inside an electrospray emitter. The capture process is monitored in real-time via next-generation biolayer interferometry (BLI). When electrospray is established from the emitter to a mass spectrometer, the analyte is immediately ionized via electrospray ionization (ESI) for HR-MS analysis. Serum, CSF, and secretion samples were analyzed using MPIE-ESI-MS. Based on the MPIE-ESI-MS results, the primary structures of β1-Tf and β2-Tf were elucidated. As Tf glycoforms, β1-Tf and β2-Tf share the amino acid sequence but contain varying N-glycans: (1) β1-Tf, the major serum-type Tf, has two G2S2 N-glycans on Asn413 and Asn611; and (2) β2-Tf, the major brain-type Tf, has an M5 N-glycan on Asn413 and a G0FB N-glycan on Asn611. The resolving power of the innovative MPIE-ESI-MS method was demonstrated in the study of β2-Tf as well as β1-Tf. Knowing the N-glycan structures on β2-Tf allows for the design of more novel test methods for β2-Tf in the future.

  View details for DOI 10.1038/s41598-023-42064-7

  View details for PubMedID 37696850

  View details for PubMedCentralID 345148

• Mass spectrometry quantitation of immunosuppressive drugs in clinical specimens using online solid-phase extraction and accurate-mass full scan-single ion monitoring. Journal of mass spectrometry and advances in the clinical lab Yeung, P. S., Miller, P., Lai-Nyugen, T. B., Cheng, P., Ibrahim, A., Shi, R., Bowen, R. A., Luo, R. Y. 2023; 28: 99-104

  Abstract

  Introduction: Therapeutic drug monitoring (TDM) of immunosuppressants is essential for optimal care of transplant patients. Immunoassays and liquid chromatography-mass spectrometry (LC-MS) are the most commonly used methods for TDM. However, immunoassays can suffer from interference from heterophile antibodies and structurally similar drugs and metabolites. Additionally, nominal-mass LC-MS assays can be difficult to optimize and are limited in the number of detectable compounds.Objectives: The aim of this study was to implement a mass spectrometry-based test for immunosuppressant TDM using online solid-phase extraction (SPE) and accurate-mass full scan-single ion monitoring (FS-SIM) data acquisition mode.Methods: LC-MS analysis was performed on a TLX-2 multi-channel HPLC with a Q-Exactive Plus mass spectrometer. TurboFlow online SPE was used for sample clean up. The accurate-mass MS was set to positive electrospray ionization mode with FS-SIM for quantitation of tacrolimus, sirolimus, everolimus, and cyclosporine A. MS2 fragmentation pattern was used for compound confirmation.Results: The method was validated in terms of precision, analytical bias, limit of quantitation, linearity, carryover, sample stability, and interference. Quantitation of tacrolimus, sirolimus, everolimus, and cyclosporine A correlated well with results from an independent reference laboratory (r=0.926-0.984).Conclusions: Accurate-mass FS-SIM can be successfully utilized for immunosuppressant TDM with good correlation with results generated by standard methods. TurboFlow online SPE allows for a simple "protein crash and shoot" sample preparation protocol. Compared to traditional MRM, analyte quantitation by FS-SIM facilitates a streamlined assay optimization process.

  View details for DOI 10.1016/j.jmsacl.2023.03.002

  View details for PubMedID 36937810

• Evaluation of a Rapid and Accessible Reverse Transcription-Quantitative PCR Approach for SARS-CoV-2 Variant of Concern Identification. Journal of clinical microbiology Yeung, P. S., Wang, H., Sibai, M., Solis, D., Yamamoto, F., Iwai, N., Jiang, B., Hammond, N., Truong, B., Bihon, S., Santos, S., Mar, M., Mai, C., Mfuh, K. O., Miller, J. A., Huang, C., Sahoo, M. K., Zehnder, J. L., Pinsky, B. A. 2022: e0017822

  Abstract

  The ability to distinguish between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) is of ongoing interest due to differences in transmissibility, responses to vaccination, clinical prognosis, and therapy. Although detailed genetic characterization requires whole-genome sequencing (WGS), targeted nucleic acid amplification tests can serve a complementary role in clinical settings, as they are more rapid and accessible than sequencing in most laboratories. We designed and analytically validated a two-reaction multiplex reverse transcription-quantitative PCR (RT-qPCR) assay targeting spike protein mutations L452R, E484K, and N501Y in reaction 1 and del69-70, K417N, and T478K in reaction 2. This assay had 95 to 100% agreement with WGS for 502 upper respiratory tract swab samples collected between 26 April 2021 and 1 August 2021, consisting of 43 Alpha, 2 Beta, 20 Gamma, 378 Delta, and 59 non-VOC infections. Validation in a separate group of 230 WGS-confirmed Omicron variant samples collected in December 2021 and January 2022 demonstrated 100% agreement. This RT-qPCR-based approach can be implemented in clinical laboratories already performing SARS-CoV-2 nucleic acid amplification tests to assist in local epidemiological surveillance and clinical decision-making.

  View details for DOI 10.1128/jcm.00178-22

  View details for PubMedID 35465708

• Development and evaluation of an RT-qPCR for the identification of the SARS-CoV-2 Omicron variant. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology Sibai, M., Wang, H., Yeung, P. S., Sahoo, M. K., Solis, D., Mfuh, K. O., Huang, C., Yamamoto, F., Pinsky, B. A. 2022; 148: 105101

  View details for DOI 10.1016/j.jcv.2022.105101

  View details for PubMedID 35151048