Development of blood biomarkers for drug-induced liver injury: An evaluation of their potential for risk assessment and diagnostics

Molecular Diagnosis and Therapy

Volumn 17, Issue 6, 2013, Pages 343-354

  Amacher, David E ^a   Schomaker, Shelli J ^b   Aubrecht, Jiri ^b  

^a Toxadvisor Toxicology Consulting   (United States)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; CYTOKINE; MESSENGER RNA; MICRORNA; NUCLEIC ACID; PROTEIN DERIVATIVE;

EXCRETION; HUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEOMICS; REVIEW; RISK ASSESSMENT; TOXIC HEPATITIS;

ANIMALS; BIOLOGICAL MARKERS; CYTOKINES; DATABASES, BIBLIOGRAPHIC; DISEASE MODELS, ANIMAL; DRUG-INDUCED LIVER INJURY; HUMANS; LIVER; METABOLOMICS; MICRORNAS; RISK ASSESSMENT; RISK FACTORS; RNA, MESSENGER;

EID: 84885682508     PISSN: 11771062     EISSN: 11792000     Source Type: Journal    
DOI: 10.1007/s40291-013-0049-0     Document Type: Review

References (102)

1. Zhang M, Chen M, Tong W. Is toxicogenomics a more reliable and sensitive biomarker than conventional indicators from rats to predict drug-induced liver injury in humans? Chem Res Toxicol. 2012;25(1):122-9.
2. Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, Lilly P, Sanders J, Sipes G, Bracken W, Dorato M, Van Deun K, Smith P, Berger B, Heller A. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol. 2000;32(1):56-67.
3. Ostapowicz G, Fontana RJ, Schiodt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002;137:947-54.
4. Lammert C, Einarsson S, Saha C, Niklasson A, Bjornsson E, Chalasani N. Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: search for signals. Hepatology. 2008;47(6):2003-9.
5. Verma S, Kaplowitz N. Diagnosis, management and prevention of drug-induced liver injury. Gut. 2009;58(11):1555-64.
6. Lee WM. Drug-induced hepatotoxicity. N Engl J Med. 2003;349(5):474-85.
7. Chalasani N, Björnsson E. Risk factors for idiosyncratic drug-induced liver injury. Gastroenterology. 2010;138(7):2246-59.
8. Corsini A, Ganey P, Ju C, Kaplowitz N, Pessayre D, Roth R, Watkins PB, Albassam M, Liu B, Stancic S, Suter L, Bortolini M. Current challenges and controversies in drug-induced liver injury. Drug Saf. 2012;35(12):1099-117.
9. Tarantino G, Conca P, Basile V, Gentile A, Capone D, Polichetti G, Leo E. A prospective study of acute drug-induced liver injury in patients suffering from non-alcoholic fatty liver disease. Hepatol Res. 2007;37(6):410-5.
10. Farmer AD, Brind A. Drug-induced liver injury. Medicine. 2011;39(3):536-40.
11. Lucena MI, Molokhia M, Shen Y, Spanish DILI Registry, EUDRAGENE, DILIN, DILIGEN, International SAEC, et al. Susceptibility to amoxicillin-clavulanate- induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology. 2011;141(1):338-47.
12. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89-95.
13. FDA. Guidance for Industry. pharmacogenomic data submission (2005). http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/UCM079849.pdf.
14. Boone L, Meyer D, Cusick P, Ennulat D, Bolliger AP, Everds N, Meador V, Elliott G, Honor D, Bounous D, Jordan H. Selection and interpretation of clinical pathology indicators of hepatic injury in preclinical studies. Vet Clin Pathol. 2005;34(3):182-8.
15. Weingand K, Brown G, Hall R, Davies D, et al. Harmonization of animal clinical pathology testing in toxicity and safety studies. The Joint Scientific Committee for International Harmonization of Clinical Pathology Testing. Fundam Appl Toxicol. 1996;29(2):198-201.
16. Evans GO. Assessment of hepatotoxicty. In: Animal clinical chemistry. 2nd ed. Boca Raton: CRC Press; 2009. p. 37-66.
17. FDA. Guidance for Industry. Drug-induced liver injury: premarketing clinical evaluation. 2007. http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/UCM174090.pdf.
18. Temple R. Hy's law: predicting serious hepatotoxicity. Pharmacoepidemiol Drug Saf. 2006;15(4):241-3.
19. Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, Hunt CM, Wilke RA, Avigan M, Kaplowitz N, Bjornsson E, Daly AK. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011;89(6):806-15.
20. Schomaker S, Warner R, Bock J, Johnson K, Potter D, Van Winkle J, Aubrecht J. Assessment of emerging biomarkers of liver injury in human subjects. Toxicol Sci. 2013;132(2):276-83.
21. Lee WM, Senior JR. Recognizing drug-induced liver injury: current problems, possible solutions. Toxicol Pathol. 2005;33(1):155-64.
22. Paulovich AG, Whiteaker JR, Hoofnagle AN, Wang P. The interface between biomarker discovery and clinical validation: the tar pit of the protein biomarker pipeline. Proteomics Clin Appl. 2008;2(10-11):1386-402.
23. Kondrat RW, McClusky GA, Cooks RG. Multiple reaction monitoring in mass spectrometry/mass spectrometry for direct analysis of complex mixtures. Anal Chem. 1978;50(14):2017-21.
24. Angel TE, Aryal UK, Hengel SM, Baker ES, Kelly RT, Robinson EW, Smith RD. Mass spectrometry-based proteomics: existing capabilities and future directions. Chem Soc Rev. 2012;41(10):3912-28.
25. Yang J, Qu L. deepBase: annotation and discovery of microRNAs and other noncoding RNAs from deep-sequencing data, vol 822. 1st ed. New York: Springer Science Business Media; 2012. p. 233-48.
26. Matheis K, Laurie D, Andriamandroso C, Arber N, Badimon L, Benain X, Bendjama K, Clavier I, Colman P, Firat H, Goepfert J, Hall S, Joos T, Kraus S, Kretschmer A, Merz M, Padro T, Planatscher H, Rossi A, Schneiderhan-Marra N, Schuppe-Koistinen I, Thomann P, Vidal JM, Molac B. A generic operational strategy to qualify translational safety biomarkers. Drug Discov Today. 2011;13-14:600-8.
27. FDA Guidance for Industry Bioanalytical Method Validation. 2001. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/UCM070107.pdf.
28. Lee JW, Devanarayan V, Barrett YC, Weiner R, Allinson J, Fountain S, Keller S, Weinryb I, Green M, Duan L, Rogers JA, Millham R, O'Brien PJ, Sailstad J, Khan M, Ray C, Wagner JA. Fit-for-purpose method development and validation for successful biomarker measurement. Pharm Res. 2006;23(2):312-28.
29. Lee JW, Hall M. Method validation of protein biomarkers in support of drug development or clinical diagnosis/prognosis. J Chromatogr B Analyt Technol Biomed Life Sci. 2009;877(13):1259-71.
30. Köhler K, Seitz H. Validation processes of protein biomarkers in serum - a cross platform comparison. Sensors (Basel). 2012;12(9):12710-28.
31. FDA. Guidance for industry. Qualification process for drug development tools. 2010. http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/UCM230597.pdf.
32. Goodsaid F, Frueh F. Biomarker qualification pilot process at the US Food and Drug Administration. AAPS J. 2007;9(1):E105-8.
33. Goodsaid F, Papaluca M. Evolution of biomarker qualification at the health authorities. Nat Biotechnol. 2010;28(5):441-3.
34. Goodsaid FM, Frueh FW, Mattes W. Strategic paths for biomarker qualification. Toxicology. 2008;245(3):219-23.
35. FDA. Biomarker Qualification Program. 2012. http://www.fda.gov/Drugs/ DevelopmentApprovalProcess/DrugDevelopmentToolsQualificationProgram/ucm284076. htm. Accessed 12 April 2013.
36. Collings FB, Vaidya VS. Novel technologies for the discovery and quantitation of biomarkers of toxicity. Toxicology. 2008;245:167-74.
37. Anderson NL. Counting the proteins in plasma. Clin Chem. 2010;56(11):1775-6.
38. Rifai N, Gillette MA, Carr SA. Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol. 2006;24(8):971-83.
39. Ozer J, Reagan W, Schomaker S, Palandra J, Baratta M, Ramaiah S. Biomarkers in medicine, drug discovery, and environmental health. 1st ed. Hoboken: Wiley; 2010. p. 203-36.
40. Bell LN, Vuppalanchi R, Watkins PB, Bonkovsky HL, Serrano J, Fontana RJ, Wang M, Rochon J, Chalasani N, US Drug-Induced Liver Injury Network (DILIN) Research Group. Serum proteomic profiling in patients with drug-induced liver injury. Aliment Pharmacol Ther. 2012;35:600-12.
41. Hoofnagle AN, Becker JO, Oda MN, Cavigiolio G, Mayer P, Vaisar T. Multiple-reaction monitoring-mass spectrometric assays can accurately measure the relative protein abundance in complex mixtures. Clin Chem. 2012;58(4):777-81.
42. Picotti P, Aebersold R. Selected reaction monitoring-based proteomics: workflows, potential, pitfalls and future directions. Nat Methods. 2012;9(6):555-66.
43. Eissler CL, Bremmer SC, Martinez JS, Parker LL, Charbonneau H, Hall MC. A general strategy for studying multisite protein phosphorylation using label-free selected reaction monitoring mass spectrometry. Anal Biochem. 2011;418(2):267-75.
44. Anderson NL, Anderson NG, Haines LR, Hardie DB, Olafson RW, Pearson TW. Mass spectrometric quantitation of peptides and proteins using Stable Isotope Standards and Capture by Anti-Peptide Antibodies (SISCAPA). J Proteome Res. 2004;3(2):235-44.
45. Anderson L, Hunter CL. Quantitative mass spectrometric multiple reaction monitoring assays for major plasma proteins. Mol Cell Proteomics. 2006;5(4):573-88.
46. Antoine DJ, Jenkins RE, Dear JW, Williams DP, McGill MR, Sharpe MR, Craig DG, Simpson KJ, Jaeschke H, Park BK. Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity. J Hepatol. 2012;56(5):1070-9.
47. Bailey WJ, Holder D, Patel H, Devlin P, Gonzalez RJ, Hamilton V, Muniappa N, Hamlin DM, Thomas CE, Sistare FD, Glaab WE. A performance evaluation of three drug-induced liver injury biomarkers in the rat: alpha-glutathione S-transferase, arginase 1, and 4-hydroxyphenyl-pyruvate dioxygenase. Toxicol Sci. 2012;130(2):229-44.
48. Amacher DE, Adler R, Herath A, Townsend RR. Use of proteomic methods to identify serum biomarkers associated with rat liver toxicity or hypertrophy. Clin Chem. 2005;51(10):1796-803.
49. Laverty HG, Antoine DJ, Benson C, Chaponda M, Williams D, Kevin Park B. The potential of cytokines as safety biomarkers for drug-induced liver injury. Eur J Clin Pharmacol. 2010;66(10):961-76.
50. Lacour S, Gautier JC, Pallardy M, Roberts R. Cytokines as potential biomarkers of liver toxicity. Cancer Biomark. 2005;1(1):29-39.
51. Tarrant JM. Blood cytokines as biomarkers of in vivo toxicity in preclinical safety assessment: considerations for their use. Toxicol Sci. 2010;117(1):4-16.
52. Etheridge A, Lee I, Hood L, Galas D, Wang K. Extracellular microRNA: a new source of biomarkers. Mutat Res. 2011;717(1-2):85-90.
53. Su Z, Li Z, Chen T, Li QZ, Fang H, Ding D, Ge W, Ning B, Hong H, Perkins RG, Tong W, Shi L. Comparing next-generation sequencing and microarray technologies in a toxicological study of the effects of aristolochic acid on rat kidneys. Chem Res Toxicol. 2011;24(9):1486-93.
54. Gullapalli RR, Desai KV, Santana-Santos L, Kant JA, Becich MJ. Next generation sequencing in clinical medicine: challenges and lessons for pathology and biomedical informatics. J Pathol Inform. 2012;3:40.
55. Wang K, Yuan Y, Li H, Cho JH, Huang D, Gray L, Qin S, Galas DJ. The spectrum of circulating RNA: a window into systems toxicology. Toxicol Sci. 2013;132(2):478-92.
56. Su YW, Chen X, Jiang ZZ, Wang T, Wang C, Zhang Y, Wen J, Xue M, Zhu D, Zhang Y, Su YJ, Xing TY, Zhang CY, Zhang LY. A panel of serum microRNAs as specific biomarkers for diagnosis of compound- and herb-induced liver injury in rats. PLoS One. 2012;7(5):e37395.
57. FDA. MicroArray Quality Control (MAQC). 2011. http://www.fda.gov/ ScienceResearch/BioinformaticsTools/MicroarrayQualityControlProject/default.htm.
58. Swaminathan R, Butt AN. Circulating nucleic acids in plasma and serum: recent development. Ann New York Acad Sci. 2006;1075:1-9.
59. Fleischacker M. Biology of circulating mRNA: still questions than answers? Ann. New York Acad Sci. 2006;1075:40-9.
60. Cocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artifacts no more. Trends Cell Biol. 2009;19:43-51.
61. Kudo Y, Ochi T, Shimada H, Ogawa S, Shinjo K. Utility of plasma circulating mRNA as a marker to detect hepatic injury. J Vet Med Sci. 2008;70(9):993-5.
62. Wetmore BA, Brees DJ, Singh R, Watkins PB, Andersen ME, Loy J, Thomas RS. Quantitative analyses and transcriptomic profiling of circulating messenger RNAs as biomarkers of rat liver injury. Hepatology. 2010;51(6):2127-39.
63. Miyamoto M, Yanai M, Ookubo S, Awasaki N, Takami K, Imai R. Detection of cell-free, liver-specific mRNAs in peripheral blood from rats with hepatotoxicity: a potential toxicological biomarker for safety evaluation. Toxicol Sci. 2008;106(2):538-45.
64. Okubo S, Miyamoto M, Takami K, Kanki M, Ono A, Nakatsu N, Yamada H, Ohno Y, Urushidani T. Identification of novel liver-specific mRNAs in plasma for biomarkers of drug-induced liver injury and quantitative evaluation in rats treated with various hepatotoxic compounds. Toxicol Sci. 2013;132(1):21-31.
65. Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell. 2009;136(4):642-55.
66. Wang K, Yuan Y, Cho JH, McClarty S, Baxter D, Galas DJ. Comparing the microRNA spectrum between serum and plasma. PLoS One. 2012;7(7):e41561.
67. Kroh E, Parkin R, Mitchell P, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods. 2010;50:298-301.
68. Williams AE. Functional aspects of animal microRNAs. Cell Mol Life Sci. 2008;65(4):545-62.
69. Wang K, Zhang S, Marzolf B, Troisch P, Brightman A, Hu Z, Hood LE, Galas DJ. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA. 2009;106(11):4402-7.
70. Elfimova N, Schlattjan M, Sowa JP, Dienes HP, Canbay A, Odenthal M. Circulating microRNAs: promising candidates serving as novel biomarkers of acute hepatitis. Front Physiol. 2012;3:476.
71. Tsai WC, Hsu SD, Hsu CS, Lai TC, Chen SJ, Shen R, Huang Y, Chen HC, Lee CH, Tsai TF, Hsu MT, Wu JC, Huang HD, Shiao MS, Hsiao M, Tsou AP. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Invest. 2012;122(8):2884-97.
72. Jopling C. Liver-specific microRNA-122: biogenesis and function. RNA Biol. 2012;9(2):137-42.
73. Laterza OF, Lim L, Garrett-Engele PW, Vlasakova K, Muniappa N, Tanaka WK, Johnson JM, Sina JF, Fare TL, Sistare FD, Glaab WE. Plasma microRNAs as sensitive and specific biomarkers of tissue injury. Clin Chem. 2009;55(11):1977-83.
74. Zhang Y, Jia Y, Zheng R, Guo Y, Wang Y, Guo H, Fei M, Sun S. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chem. 2010;56(12):1830-8.
75. Starckx S, Batheja A, Verheyen GR, Jonghe SD, Steemans K, Dijck BV, Singer M, Bogdan N, Snoeys J, Vinken P, Sasaki JC, Gompel JV, Guzzie-Peck P, Lampo A, Lammens L. Evaluation of miR-122 and other biomarkers in distinct acute liver injury in rats. Toxicol Pathol. 2013;41(5):795-804.
76. Starkey Lewis PJ, Dear J, Platt V, Simpson KJ, Craig DG, Antoine DJ, French NS, Dhaun N, Webb DJ, Costello EM, Neoptolemos JP, Moggs J, Goldring CE, Park BK. Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology. 2011;54(5):1767-76.
77. Antoine DJ, Dear JW, Starkey-Lewis P, Platt V, Coyle J, Masson M, Thanacoody RH, Gray AJ, Webb DJ, Moggs JG, Bateman DN, Goldring CE, Park BK. Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital. Hepatology. 2013. doi: 10.1002/hep.26294.
78. Qi P, Cheng SQ, Wang H, Li N, Chen YF, Gao CF. Serum microRNAs as biomarkers for hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection. PLoS One. 2011;6(12):e28486.
79. Cermelli S, Ruggieri A, Marrero JA, Ioannou GN, Beretta L. Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PLoS One. 2011;6(8):e23937.
80. Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, Huang L, Li H, Tan W, Wang C, Lin D. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50(2):136-42.
81. Nicholson JK, Connelly J, Lindon JC, Holmes E. Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov. 2002;1(2):153-61.
82. Wang JH, Byun J, Pennathur S. Analytical approaches to metabolomics and applications to systems biology. Semin Nephrol. 2010;30(5):500-11.
83. MSI: Metabonomics Standards Initiative. http://msi-workgroups. sourceforge.net/. Accessed 12 April 2013.
84. Kumar BS, Chung BC, Kwon OS, Jung BH. Discovery of common urinary biomarkers for hepatotoxicity induced by carbon tetrachloride, acetaminophen and methotrexate by mass spectrometry-based metabolomics. J Appl Toxicol. 2012;32(7):505-20.
85. Sun J, Schnackenberg LK, Beger RD. Studies of acetaminophen and metabolites in urine and their correlations with toxicity using metabolomics. Drug Metab Lett. 2009;3(3):130-6.
86. Coen M, Goldfain-Blanc F, Rolland-Valognes G, Walther B, Robertson DG, Holmes E, Lindon JC, Nicholson JK. Pharmacometabonomic investigation of dynamic metabolic phenotypes associated with variability in response to galactosamine hepatotoxicity. J Proteome Res. 2012;11(4):2427-40.
87. Zira A, Kostidis S, Theocharis S, Sigala F, Engelsen SB, Andreadou I, Mikros E. 1H NMR-based metabonomics approach in a rat model of acute liver injury and regeneration induced by CCl4 administration. Toxicology. 2013;303:115-24.
88. Gika HG, Ji C, Theodoridis GA, Michopoulos F, Kaplowitz N, Wilson ID. Investigation of chronic alcohol consumption in rodents via ultra-high- performance liquid chromatography-mass spectrometry based metabolite profiling. J Chromatogr A. 2012;1259:128-37.
89. Clayton TA, Lindon JC, Cloarec O, Antti H, Charuel C, Hanton G, Provost JP, Le Net JL, Baker D, Walley RJ, Everett JR, Nicholson JK. Pharmaco-metabonomic phenotyping and personalized drug treatment. Nature. 2006;440(7087):1073-7.
90. Winnike JH, Li Z, Wright FA, Macdonald JM, O'Connell TM, Watkins PB. Use of pharmaco-metabonomics for early prediction of acetaminophen-induced hepatotoxicity in humans. Clin Pharmacol Ther. 2010;88(1):45-51.
91. Woolbright BL, Jaeschke H. Novel insight into mechanisms of cholestatic liver injury. World J Gastroenterol. 2012;18(36):4985-93.
92. Darkoh C, Lichtenberger LM, Ajami N, Dial EJ, Jiang ZD, DuPont HL. Bile acids improve the antimicrobial effect of rifaximin. Antimicrob Agents Chemother. 2010;54(9):3618-24.
93. Shimada T, Nakanishi T, Toyama A, Yamauchi S, Kanzaki A, Fujiwake H, Sato TA, Ikegawa M. Potential implications for monitoring serum bile acid profiles in circulation with serum proteome for carbon tetrachloride-induced liver injury/regeneration model in mice. J Proteome Res. 2010;9(9):4490-500.
94. Kawai H, Kudo N, Kawashima Y, Mitsumoto A. Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats. J Toxicol Sci. 2009;34(1):27-38.
95. Trottier J, Białek A, Caron P, Straka RJ, Milkiewicz P, Barbier O. Profiling circulating and urinary bile acids in patients with biliary obstruction before and after biliary stenting. PLoS One. 2011;6(7):e22094.
96. Lake AD, Novak P, Shipkova P, Aranibar N, Robertson D, Reily MD, Lu Z, Lehman-McKeeman LD, Cherrington NJ. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease. Toxicol Appl Pharmacol. 2013;268(2):132-40.
97. Yamazaki M, Miyake M, Sato H, Masutomi N, Tsutsui N, Adam KP, Alexander DC, Lawton KA, Milburn MV, Ryals JA, Wulff JE, Guo L. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats. Toxicol Appl Pharmacol. 2013;268(1):79-89.
98. Ellinger-Ziegelbauer H, Adler M, Amberg A, Brandenburg A, Callanan JJ, Connor S, Fountoulakis M, Gmuender H, Gruhler A, Hewitt P, Hodson M, Matheis KA, McCarthy D, Raschke M, Riefke B, Schmitt CS, Sieber M, Sposny A, Suter L, Sweatman B, Mally A. The enhanced value of combining conventional and "omics" analyses in early assessment of drug-induced hepatobiliary injury. Toxicol Appl Pharmacol. 2011;252(2):97-111.
99. Hortin GL. Can mass spectrometric protein profiling meet desired standards of clinical laboratory practice? Clin Chem. 2005;51(1):3-5.
100. Anderson NL, Ptolemy AS, Rifai N. The riddle of protein diagnostics: future bleak or bright? Clin Chem. 2013;59(1):194-7.
101. Carr SA, Anderson L. Protein quantitation through targeted mass spectrometry: the way out of biomarker purgatory? Clin Chem. 2008;11:1749-1752 (editorial).
102. Anderson NL. The clinical plasma proteome: a survey of clinical assays for proteins in plasma and serum. Clin Chem. 2010;56(2):177-85.