Analysis of significant protein abundance from multiple reaction-monitoring data

Published on Dec 1, 2018in BMC Systems Biology2.048
· DOI :10.1186/s12918-018-0656-9
Jongsu Jun (SNU: Seoul National University), Jungsoo Gim6
Estimated H-index: 6
(SNU: Seoul National University)
+ 14 AuthorsTaesung Park36
Estimated H-index: 36
(SNU: Seoul National University)
Discovering reliable protein biomarkers is one of the most important issues in biomedical research. The ELISA is a traditional technique for accurate quantitation of well-known proteins. Recently, the multiple reaction-monitoring (MRM) mass spectrometry has been proposed for quantifying newly discovered protein and has become a popular alternative to ELISA. For the MRM data analysis, linear mixed modeling (LMM) has been used to analyze MRM data. MSstats is one of the most widely used tools for MRM data analysis that is based on the LMMs. However, LMMs often provide various significance results, depending on model specification. Sometimes it would be difficult to specify a correct LMM method for the analysis of MRM data. Here, we propose a new logistic regression-based method for Significance Analysis of Multiple Reaction Monitoring (LR-SAM). Through simulation studies, we demonstrate that LMM methods may not preserve type I error, thus yielding high false- positive errors, depending on how random effects are specified. Our simulation study also shows that the LR-SAM approach performs similarly well as LMM approaches, in most cases. However, LR-SAM performs better than the LMMs, particularly when the effects sizes of peptides from the same protein are heterogeneous. Our proposed method was applied to MRM data for identification of proteins associated with clinical responses of treatment of 115 hepatocellular carcinoma (HCC) patients with the tyrosine kinase inhibitor sorafenib. Of 124 candidate proteins, LMM approaches provided 6 results varying in significance, while LR-SAM, by contrast, yielded 18 significant results that were quite reproducibly consistent. As exemplified by an application to HCC data set, LR-SAM more effectively identified proteins associated with clinical responses of treatment than LMM did.
  • References (43)
  • Citations (0)
📖 Papers frequently viewed together
46 Citations
19 Citations
1 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Georgios Efstathiou (University of Oxford)H-Index: 4
#2Andreas N. Antonakis (UoC: University of Crete)H-Index: 1
Last. Ioannis Iliopoulos (UoC: University of Crete)H-Index: 16
view all 11 authors...
Author(s): Efstathiou, G; Antonakis, AN; Pavlopoulos, GA; Theodosiou, T; Divanach, P; Trudgian, DC; Thomas, B; Papanikolaou, N; Aivaliotis, M; Acuto, O; Iliopoulos, I | Abstract: © 2017 The Author(s). Profiling of proteome dynamics is crucial for understanding cellular behavior in response to intrinsic and extrinsic stimuli and maintenance of homeostasis. Over the last 20 years, mass spectrometry (MS) has emerged as the most powerful tool for large-scale identification and characterization of pr...
13 CitationsSource
#1James D.R. Knight (Lunenfeld-Tanenbaum Research Institute)H-Index: 19
#2Hyungwon Choi (Agency for Science, Technology and Research)H-Index: 31
Last. Anne-Claude Gingras (U of T: University of Toronto)H-Index: 82
view all 7 authors...
30 CitationsSource
#1Hyun-Soo KimH-Index: 38
#2Su Jong YuH-Index: 22
Last. Youngsoo KimH-Index: 39
view all 14 authors...
: Sorafenib is the only standard treatment for unresectable hepatocellular carcinoma (HCC), but it provides modest survival benefits over placebo, necessitating predictive biomarkers of the response to sorafenib. Serum samples were obtained from 115 consecutive patients with HCC before sorafenib treatment and analyzed by multiple reaction monitoring-mass spectrometry (MRM-MS) and ELISA to quantify candidate biomarkers. We verified a triple-marker panel to be predictive of the response to sorafen...
7 CitationsSource
#1Anna PursiheimoH-Index: 2
#2Anni P. VehmasH-Index: 4
Last. Laura L. EloH-Index: 25
view all 10 authors...
As tools for quantitative label-free mass spectrometry (MS) rapidly develop, a consensus about the best practices is not apparent. In the work described here we compared popular statistical methods for detecting differential protein expression from quantitative MS data using both controlled experiments with known quantitative differences for specific proteins used as standards as well as “real” experiments where differences in protein abundance are not known a priori. Our results suggest that da...
22 CitationsSource
#1Hussein N. Yassine (SC: University of Southern California)H-Index: 14
#2Angela M. Jackson (UVic: University of Victoria)H-Index: 18
Last. Christoph H. Borchers (UVic: University of Victoria)H-Index: 58
view all 7 authors...
The oxidative modification of apolipoprotein A-I ‘s methionine148(M148) is associated with defective HDL function in vitro. Multiple Reaction Monitoring (MRM) is a mass spectrometric technique that can be used to quantitate post-translational modifications. In this study, we developed an MRM assay to monitor the abundance ratio of the peptide containing oxidized M148 to the native peptide in Apo A-I. Measurement of the oxidized-to-unoxidized-M148 ratio was reproducible (CV<5%). The extent of met...
18 CitationsSource
#1X QiH-Index: 9
#2Kevin Tak-Pan NgH-Index: 27
Last. Kwan ManH-Index: 26
view all 13 authors...
// Xiang Qi 1 , Kevin Tak Pan Ng 1 , Qi Zhou Lian 2 , Xiao Bing Liu 1 , Chang Xian Li 1 , Wei Geng 1 , Chang Chun Ling 1 , Yuen Yuen Ma 1 , Wai Ho Yeung 1 , Wen Wei Tu 3 , Sheung Tat Fan 1 , Chung Mau Lo 1 , Kwan Man 1 1 Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China. 2 Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China. 3 Department of Paediatrics & Adolescent Medicine, The University of Hong Kong, Pokfulam...
21 CitationsSource
#1Mehdi MesriH-Index: 1
Systematic studies of the cancer genome have generated a wealth of knowledge in recent years. These studies have uncovered a number of new cancer genes not previously known to be causal targets in cancer. Genetic markers can be used to determine predisposition to tumor development, but molecularly targeted treatment strategies are not widely available for most cancers. Precision care plans still must be developed by understanding and implementing basic science research into clinical treatment. P...
16 CitationsSource
#1Maxime RonotH-Index: 25
#2Mohamed BouattourH-Index: 14
Last. Sandrine FaivreH-Index: 43
view all 11 authors...
Introduction. Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), mayunderestimateactivity and does not predict survival in patients with hepatocellular carcinoma (HCC) treated with sorafenib.This study assessed the value of alternative radiological criteria to evaluate response in HCC patients treated with sorafenib. Patients and Methods. A retrospective blinded central analysis was performed of computed tomography (CT) scans from baseline and the first tumor evaluation in c...
60 CitationsSource
#1Maria Frantzi (Academy of Athens)H-Index: 11
#2Akshay V. Bhat (Charité)H-Index: 6
Last. Agnieszka Latosinska (Charité)H-Index: 10
view all 3 authors...
Biomarker research is continuously expanding in the field of clinical proteomics. A combination of different proteomic–based methodologies can be applied depending on the specific clinical context of use. Moreover, current advancements in proteomic analytical platforms are leading to an expansion of biomarker candidates that can be identified. Specifically, mass spectrometric techniques could provide highly valuable tools for biomarker research. Ideally, these advances could provide with biomark...
64 CitationsSource
#1Steven A. Carr (Broad Institute)H-Index: 90
#2Susan E. Abbatiello (Broad Institute)H-Index: 11
Last. Susan T. Weintraub (University of Texas Health Science Center at San Antonio)H-Index: 41
view all 45 authors...
Adoption of targeted mass spectrometry (MS) approaches such as multiple reaction monitoring (MRM) to study biological and biomedical questions is well underway in the proteomics community. Successful application depends on the ability to generate reliable assays that uniquely and confidently identify target peptides in a sample. Unfortunately, there is a wide range of criteria being applied to say that an assay has been successfully developed. There is no consensus on what criteria are acceptabl...
276 CitationsSource
Cited By0