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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 919))

Abstract

Properly performed, biomarker discovery can lead to effective candidates that can ultimately serve as predictors of disease, medical condition, define therapeutic parameters, and many other applications in medicine. Preferably, biomarkers comprise a panel of indicators, e.g. proteins and/or peptides that can be predictive or diagnostic of the medical condition of interest. Emphasis here is placed on “panel,” as single candidates are rarely sufficient to provide the necessary sensitivity and specificity. To develop an effective panel that survives the development process described in Chap. 19, proper experimental design and attention to important statistical parameters are critical to ensure success. Errors in discovery can lead to an inefficient use of expensive resources, as these may not be uncovered until the latter stages in biomarker development. Hence, accuracy, precision, and an estimate of the power of the proposed analyses are critical in the discovery of the panel of candidate biomarkers by proteomic methods, as is the selection of statistical approaches to refine and appropriately reduce the dataset for subsequent confirmatory assays.

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References

  1. Glanz SA (2005) Primer of biostatistics. McGraw-Hill, New York

    Google Scholar 

  2. (2005) Special issue: exploring the human plasma proteome. The HUPO Plasma Proteome Project (HPPP). Proteomics 5:3223–3549

    Google Scholar 

  3. Richter R, Schulz-Knappe P, Schrader M, Standker L, Jurgens M, Tammen H, Forssmann W-G (1999) Composition of the peptide fraction in human blood plasma: database of circulating human peptides. J Chromatogr B Biomed Sci Appl 726:25–35

    Article  CAS  PubMed  Google Scholar 

  4. Villanueva J, Martorella AJ, Lawlor K, Philip J, Fleisher M, Robbins RJ, Tempst P (2006) Serum peptidome patterns that distinguish metastatic thyroid carcinoma from cancer-free controls are unbiased by gender and age. Mol Cell Proteomics 5:1840–1852

    Article  CAS  PubMed  Google Scholar 

  5. Pretzer E, Wiktorowicz JE (2008) Saturation fluorescence labeling of proteins for proteomic analyses. Anal Biochem 374:250–262

    Article  CAS  PubMed  Google Scholar 

  6. Tyagarajan K, Pretzer EL, Wiktorowicz JE (2003) Thiol-reactive dyes for fluorescence labeling of proteomic samples. Electrophoresis 24:2348–2358

    Article  CAS  PubMed  Google Scholar 

  7. Miseta A, Csutora P (2000) Relationship between the occurrence of cysteine in proteins and the complexity of organisms. Mol Biol Evol 17:1232–1239

    Article  CAS  PubMed  Google Scholar 

  8. Wiktorowicz JE, Stafford S, Rea H, Urvil P, Soman K, Kurosky A, Perez-Polo JR, Savidge TC (2011) Quantification of cysteinyl S-nitrosylation by fluorescence in unbiased proteomic studies. Biochemistry 50:5601–5614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yao X, Freas A, Ramirez J, Demirev PA, Fenselau C (2001) Proteolytic 18O labeling for comparative proteomics: model studies with two serotypes of adenovirus. Anal Chem 73:2836–2842

    Article  CAS  PubMed  Google Scholar 

  10. Miyagi M, Rao KCS (2007) Proteolytic 18O-labeling strategies for quantitative proteomics. Mass Spectrom Rev 26:121–136

    Article  CAS  PubMed  Google Scholar 

  11. Khedr A, Hegazy M, Kamal A, Shehata MA (2015) Profiling of esterified fatty acids as biomarkers in the blood of dengue fever patients using a microliter-scale extraction followed by gas chromatography and mass spectrometry. J Sep Sci 38:316–324

    Article  CAS  PubMed  Google Scholar 

  12. Poole-Smith BK, Gilbert A, Gonzalez AL, Beltran M, Tomashek KM, Ward BJ, Hunsperger EA, Ndao M (2014) Discovery and characterization of potential prognostic biomarkers for dengue hemorrhagic fever. Am J Trop Med Hyg 91:1218–1226

    Article  PubMed  PubMed Central  Google Scholar 

  13. Thayan R, Huat TL, See LL, Tan CP, Khairullah NS, Yusof R, Devi S (2009) The use of two-dimension electrophoresis to identify serum biomarkers from patients with dengue haemorrhagic fever. Trans R Soc Trop Med Hyg 103:413–419

    Article  CAS  PubMed  Google Scholar 

  14. Lee CY, Seet RC, Huang SH, Long LH, Halliwell B (2009) Different patterns of oxidized lipid products in plasma and urine of dengue fever, stroke, and Parkinson’s disease patients: cautions in the use of biomarkers of oxidative stress. Antioxid Redox Signal 11:407–420

    Article  CAS  PubMed  Google Scholar 

  15. Brasier AR, Garcia J, Wiktorowicz JE, Spratt HM, Comach G, Ju H, Recinos A 3rd, Soman K, Forshey BM, Halsey ES, Blair PJ, Rocha C, Bazan I, Victor SS, Wu Z, Stafford S, Watts D, Morrison AC, Scott TW, Kochel TJ (2012) Discovery proteomics and nonparametric modeling pipeline in the development of a candidate biomarker panel for dengue hemorrhagic fever. Clin Transl Sci 5:8–20

    Article  PubMed  PubMed Central  Google Scholar 

  16. Brasier AR, Zhao Y, Wiktorowicz JE, Spratt HM, Nascimento EJM, Cordeiro MT, Soman KV, Ju H, Recinos A, Stafford S, Wu Z, Marques ETA, Vasilakis N (2015) Molecular classification of outcomes from dengue virus −3 infections. J Clin Virol 64:97–106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. WHO (2002) Control of chagas’ disease. Second report of the WHO Expert Committee. WHO Tech Rep Ser 905:1–109, Geneva

    Google Scholar 

  18. Duran-Rehbein GA, Vargas-Zambrano JC, Cuellar A, Puerta CJ, Gonzalez JM (2014) Mammalian cellular culture models of Trypanosoma cruzi infection: a review of the published literature. Parasite 21:38

    Article  PubMed  PubMed Central  Google Scholar 

  19. Wen JJ, Dhiman M, Whorton EB, Garg NJ (2008) Tissue-specific oxidative imbalance and mitochondrial dysfunction during Trypanosoma cruzi infection in mice. Microbes Infect 10:1201–1209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gupta S, Wen JJ, Garg NJ (2009) Oxidative stress in chagas disease. Interdiscip Perspect Infect Dis 190354

    Google Scholar 

  21. Savidge TC, Urvil P, Oezguen N, Ali K, Choudhury A, Acharya V, Pinchuk I, Torres AG, English RD, Wiktorowicz JE, Loeffelholz M, Kumar R, Shi L, Nie W, Braun W, Herman B, Hausladen A, Feng H, Stamler JS, Pothoulakis C (2011) Host S-nitrosylation inhibits clostridial small molecule-activated glucosylating toxins. Nat Med 17:1136–1141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sheffield-Moore M, Wiktorowicz JE, Soman KV, Danesi CP, Kinsky MP, Dillon EL, Randolph KM, Casperson SL, Gore DC, Horstman AM, Lynch JP, Doucet BM, Mettler JA, Ryder JW, Ploutz-Snyder LL, Hsu JW, Jahoor F, Jennings K, White GR, McCammon SD, Durham WJ (2013) Sildenafil increases muscle protein synthesis and reduces muscle fatigue. Clin Transl Sci 6:463–468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to John E. Wiktorowicz .

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Wiktorowicz, J.E., Soman, K.V. (2016). Discovery of Candidate Biomarkers. In: Mirzaei, H., Carrasco, M. (eds) Modern Proteomics – Sample Preparation, Analysis and Practical Applications. Advances in Experimental Medicine and Biology, vol 919. Springer, Cham. https://doi.org/10.1007/978-3-319-41448-5_21

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