ABSTRACT
In this paper, we summarized the challenges and promises of the study of immune biomarkers. We reviewed key concepts in biomarker discovery and discussed the framework for applying these concepts in the study of the immune system and its effects on the disease -- cancer, infection, allergy, immunodeficiencies, and autoimmunity. The immune system plays a special role in biomarker discovery since it interacts with all other systems in the human body and immune biomarkers are relevant for large number of diseases.
- Adamczyk-Poplawska M et al. 2011. Proteomics for development of vaccine. J Proteomics. 74(12), 2596-616.Google ScholarCross Ref
- Adams, N. et al. 2011. PIDO, the primary immunodeficiency disease ontology. Bioinformatics. 27(22), 3193--9. Google ScholarDigital Library
- Anderson, K. S. and LaBaer, J. 2005. The sentinel within: exploiting the immune system for cancer biomarkers. J. Proteome Res. 4(4), 1123--33.Google ScholarCross Ref
- Armah, H. B. et al. 2007. Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children. Malar J. 6, 147.Google ScholarCross Ref
- Arstila, T. P. et al. 1999. A direct estimate of the human alphabeta T cell receptor diversity. Science. 286(5441), 958--61.Google ScholarCross Ref
- Azuaje, F. 2010. Bioinformatics and biomarker discovery, omic data analysis for personalised medicine. Wiley-Blackwell.Google Scholar
- Barrallo-Gimeno, A. and Nieto, M. A. 2005. The Snail genes as inducers of cell movement and survival, implications in development and cancer. Development. 132(14), 3151--61.Google ScholarCross Ref
- Bass, M. B. et al. 2010. Biomarkers as predictors of response to treatment with motesanib in patients with progressive advanced thyroid cancer. J Clin Endocrinol Metab. 95(11), 5018--27.Google ScholarCross Ref
- Bauer, J. W. et al. 2006. Elevated serum levels of interferon-regulated chemokines are biomarkers for active human systemic lupus erythematosus. PLoS Med. 3(12), e491.Google ScholarCross Ref
- Bay-Jensen, A. C. et al. 2013. Circulating protein fragments of cartilage and connective tissue degradation are diagnostic and prognostic markers of rheumatoid arthritis and ankylosing spondylitis. PLoS One. 8(1), e54504.Google ScholarCross Ref
- Bielekova, B. and Martin, R. 2004. Development of biomarkers in multiple sclerosis. Brain. 127(Pt 7), 1463--78.Google ScholarCross Ref
- Biomarkers Definitions Working Group. 2001. Biomarkers and surrogate endpoints, preferred definitions and conceptual framework. Clin Pharmacol Ther. 69(3), 89--95.Google ScholarCross Ref
- Blüggel, M. et al. 2011 Toward protein biomarkers for allergy: CD4+ T cell proteomics in allergic and nonallergic subjects sampled in and out of pollen season. J Proteome Res. 10(4), 1558--70.Google ScholarCross Ref
- Boles, J. W. et al. 2003. Generation of protective immunity by inactivated recombinant staphylococcal enterotoxin B vaccine in nonhuman primates and identification of correlates of immunity. Clin Immunol. 108, 51--9.Google ScholarCross Ref
- Brusic V and August JT. 2004. The changing field of vaccine development in the genomics era. Pharmacogenomics. 5(6), 597--600.Google ScholarCross Ref
- Brusic V et al. 1998. Data learning, understanding biological data. In Knowledge Sharing Across Biological and Medical Knowledge Based Systems, Merrill G., Pathak D.K. Ed. AAAI Press, 12--19.Google Scholar
- Brusic V et al. 2005. Information technologies for vaccine research. Expert Rev Vaccines. 4(3), 407--17.Google ScholarCross Ref
- Chen, R et al. 2013. A bayesian diagnostic system to differentiate glioblastomas from solitary brain metastases. Neuroradiol J. 26(2), 175--83.Google ScholarCross Ref
- Chen, YD et al. 2004. Artificial neural networks analysis of surface-enhanced laser desorption/ionization mass spectra of serum protein pattern distinguishes colorectal cancer from healthy population. Clin Cancer Res. 10(24), 8380--5.Google ScholarCross Ref
- Chintamaneni, M. and Bhaskar, M. 2012. Biomarkers in Alzheimer's disease, a review. ISRN Pharmacol. 984786.Google Scholar
- Cohen, I. R. 2007. Biomarkers, self-antigens and the immunological homunculus. J Autoimmun. 29:246--9.Google ScholarCross Ref
- Cromme, F. V. et al. 1994. Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas. J Exp Med. 179(1), 335--40.Google ScholarCross Ref
- Davis, M. M. 2008. A prescription for human immunology. Immunity. 29(6), 835--8.Google ScholarCross Ref
- DelaRosa, O. et al. 2006. Immunological biomarkers of ageing in man: changes in both innate and adaptive immunity are associated with health and longevity. Biogerontology. 7(5-6), 471--81.Google ScholarCross Ref
- DeNardo, D. G. et al. 2010. Interactions between lymphocytes and myeloid cells regulate pro- versus antitumor immunity. Cancer Metastasis Rev. 29(2), 309--16.Google ScholarCross Ref
- Doecke, J. D. et al. 2012. Alzheimer's disease neuroimaging initiative. Blood-based protein biomarkers for diagnosis of Alzheimer disease. Arch Neurol. 69(10), 1318--25.Google ScholarCross Ref
- Draper N and Smith H. 1981. Applied Regression Analysis, 2d Edition, New York, John Wiley & Sons, Inc.Google Scholar
- Eifan, A. O. et al. 2011. Long-term clinical and immunological effects of allergen immunotherapy. Curr Opin Allergy Clin Immunol. 11(6):586--93.Google ScholarCross Ref
- Enríquez-de-Salamanca, A., Bonini, S., and Calonge, M. 2012. Molecular and cellular biomarkers in dry eye disease and ocular allergy. Curr Opin Allergy Clin Immunol. 12, 523--33.Google ScholarCross Ref
- Feng, Z. et al. 2013. The early detection research network's specimen reference sets, paving the way for rapid evaluation of potential biomarkers. Clin Chem. 59(1), 68--74.Google ScholarCross Ref
- Franco, L. M. et al. 2013. Integrative genomic analysis of the human immune response to influenza vaccination. Elife. 2, e00299.Google ScholarCross Ref
- Frankenstein, Z. et al. 2006. The immune-body cytokine network defines a social architecture of cell interactions. Biol Direct. 1, 32.Google ScholarCross Ref
- Gibson, D. S. et al. 2010. Diagnostic and prognostic biomarker discovery strategies for autoimmune disorders. J Proteomics. 73(6), 1045--60.Google ScholarCross Ref
- Gnatenko, D. V. et al. 2010. Class prediction models of thrombocytosis using genetic biomarkers. Blood. 115(1), 7--14.Google ScholarCross Ref
- Graham WG. 2009. Missing data analysis, making it work in the real world. Annu. Rev. Psychol. 60, 549--76.Google ScholarCross Ref
- Grivennikov, S. I. et al. 2010. Immunity, inflammation, and cancer. Cell. 140(6), 883--99.Google ScholarCross Ref
- Habermann K et al. 2009. The gene expression signature of genomic instability in breast cancer is an independent predictor of clinical outcome. Int J Cancer. 124(7), 1552--64.Google ScholarCross Ref
- Haight T and Jagust J. 2012. Alzheimer's Disease Neuroimaging Initiative, relative contributions of biomarkers in Alzheimer's disease. Ann Epidemiol. 22, 868--75.Google ScholarCross Ref
- Hamilton, J. A. and Tak, P. P. 2009. The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases. Arthritis Rheum. 60(5), 1210--21.Google ScholarCross Ref
- Hanahan, D and Weinberg, R. A. 2011. Hallmarks of cancer, the next generation. Cell. 144(5), 646--74.Google ScholarCross Ref
- Heo, C. K. et al. 2012. Tumor-associated autoantibodies as diagnostic and prognostic biomarkers. BMB Rep 45(12), 677--85.Google ScholarCross Ref
- Hicklin, D. J. et al. 1999. HLA class I antigen downregulation in human cancers: T-cell immunotherapy revives an old story. Mol Med Today. 5(4), 178--86.Google ScholarCross Ref
- Hocking, R. 1976. The Analysis and Selection of Variables in Linear Regression. Biometrics. 32(1), 1--49.Google ScholarCross Ref
- Hollevoet, K. et al. 2011. Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals, a prospective longitudinal cohort study. J Thorac Oncol. 6(5), 889--95.Google ScholarCross Ref
- Hooks, J. J. et al. 1979. Immune interferon in the circulation of patients with autoimmune disease. N Engl J Med. 301(1), 5--8.Google ScholarCross Ref
- Huang, B. et al. 2005. Toll-like receptors on tumor cells facilitate evasion of immune surveillance. Cancer Res. 65(12), 5009--14.Google ScholarCross Ref
- Huang, H.C. 2009. Designing a knowledge-based system for strategic planning, a balanced scorecard perspective. Expert Systems Applicat. 36, 209--18. Google ScholarDigital Library
- Huang, Z. et al. 2009. MALDI-TOF MS combined with magnetic beads for detecting serum protein biomarkers and establishment of boosting decision tree model for diagnosis of systemic lupus erythematosus. Rheumatology (Oxford). 48(6), 626--31.Google ScholarCross Ref
- Hulka, B. S. 1990. Overview of biological markers. In Biological markers in epidemiology, Hulka, B. S., Griffith, J. D., Wilcosky, T. C. Ed. New York, Oxford University Press, 3--15.Google Scholar
- Ibelgaufts, H. 2013. COPE: Cytokines Online Pathfinder Encyclopedia. Version 31.4. DOI=http://www.copewithcytokines.de.Google Scholar
- Jacobsen, M. et al. 2007. Candidate biomarkers for discrimination between infection and disease caused by Mycobacterium tuberculosis. J Mol Med (Berl). 85(6), 613--21.Google ScholarCross Ref
- Janeway, C. A. and Jr Medzhitov, R. 2002. Innate immune recognition. Annu Rev Immunol. 20, 197--216.Google ScholarCross Ref
- Jerne, N. K. 1993. The generative grammar of the immune system. Scand J Immunol. 38, 1--9.Google ScholarCross Ref
- Joyce, A. R. and Palsson, B. Ø. 2006. The model organism as a system, integrating 'omics' data sets. Nat Rev Mol Cell Biol. 7(3), 198--210.Google ScholarCross Ref
- Kharitonov, S. A. and Barnes, P. J. 2006. Exhaled biomarkers. Chest. 130(5), 1541--6.Google ScholarCross Ref
- Kim, R. et al. 2006. Tumor-driven evolution of immunosuppressive networks during malignant progression. Cancer Res. 66(11), 5527--36.Google ScholarCross Ref
- Kirouac, D. C. et al. 2010. Dynamic interaction networks in a hierarchically organized tissue. Mol Syst Biol. 6, 417.Google ScholarCross Ref
- Klymkowsky, M. W. and Savagner, P. 2009. Epithelial-mesenchymal transition, a cancer researcher's conceptual friend and foe. Am J Pathol. 174(5), 1588--93.Google ScholarCross Ref
- Kuller, L. H. et al. 2008. INSIGHT SMART Study Group. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 5(10), e203.Google ScholarCross Ref
- Kwon D et al. 2008. A novel wavelet-based thresholding method for the pre-processing of mass spectrometry data that accounts for heterogeneous noise. Proteomics. 8, 3019--29.Google ScholarCross Ref
- Lai, D. et al. 2003. Sample size for biomarker studies, more subjects or more measurements per subject? Ann Epidemiol. 13(3), 204--8.Google ScholarCross Ref
- Lin, K. C. et al. 2007. Discriminant analysis of serum inflammatory biomarkers which differentiate pediatric appendicitis from other acute abdominal diseases. Acta Paediatr Taiwan. 48(3), 125--30.Google Scholar
- Liu, C. et al. 2008. Genome-wide association scan identifies candidate polymorphisms associated with differential response to anti-TNF treatment in rheumatoid arthritis. Mol Med. 14(9-10), 575--81.Google ScholarCross Ref
- Liu, C. et al. 2011. MALDI-TOF MS combined with magnetic beads for detecting serum protein biomarkers and establishment of boosting decision tree model for diagnosis of colorectal cancer. Int J Med Sci. 8(1), 39--47.Google ScholarCross Ref
- Liu, Z., Jiang F., Tian, G., Wang, S., Sato, F., Meltzer, S. J., and Tan, M. 2007. Sparse logistic regression with Lp penalty for biomarker identification. Stat Appl Genet Mol Biol. 6(1), 6.Google ScholarCross Ref
- Luterman, J. D. et al. 2000. Cytokine gene expression as a function of the clinical progression of Alzheimer disease dementia. Arch Neurol. 57(8), 1153--60.Google ScholarCross Ref
- Macedo, P. et al. 2009. Inflammatory biomarkers in airways of patients with severe asthma compared with non-severe asthma. Clin Exp Allergy. 39(11), 1668--76.Google ScholarCross Ref
- Mattsson, N. and Zetterberg, H. 2009. Alzheimer's disease and CSF biomarkers, key challenges for broad clinical applications. Biomark Med. 3(6), 735--7.Google ScholarCross Ref
- Mayeux, R. 2004. Biomarkers: potential uses and limitations. NeuroRx. 1(2), 182--8.Google ScholarCross Ref
- Merbl, Y. et al. 2007. Newborn humans manifest autoantibodies to defined self molecules detected by antigen microarray informatics. J Clin Invest. 117(3):712--8.Google ScholarCross Ref
- Moffitt KL et al. 2013. Inflammatory and immunological biomarkers are not related to survival in adults with Cystic Fibrosis. J Cyst Fibros. S1569--1993(13).Google Scholar
- Mrak. R. E. and Griffin, W. S. T. 2005. Potential Inflammatory biomarkers in Alzheimer's disease. J Alzheimers Dis. 8(4), 369--375.Google ScholarCross Ref
- Naylor, S. 2003. Biomarkers: current perspectives and future prospects. Expert Rev Mol Diagn. 3(5), 525--9.Google ScholarCross Ref
- Norris J et al. 2007. Processing MALDI mass spectra to improve mass spectral direct tissue analysis. Int J Mass Spectrom. 260, 212--21.Google ScholarCross Ref
- Novelli G, et al. 2008. Genetic tests and genomic biomarkers: regulation, qualification and validation. Clin Cases Miner Bone Metab. 5(2), 149--54.Google Scholar
- Novellino, L., Castelli, C., and Parmiani, G. 2005. A listing of human tumor antigens recognized by T cells: March 2004 update. Cancer Immunol Immunother. 54(3), 187--207.Google ScholarCross Ref
- Olsen, L. R., Zhang, G. L., Olsen, L. R., Reinherz, E. L., and Brusic, V. 2011. FLAVIdB, a data mining system for knowledge discovery in flaviviruses with direct applications in immunology and vaccinology. Immunome Res. 7(3), 1--9.Google Scholar
- Pappalardo, F. et al. 2009. ImmunoGrid, an integrative environment for large-scale simulation of the immune system for vaccine discovery, design and optimization. Brief Bioinform. 10(3), 330--40.Google ScholarCross Ref
- Parida, S. K. and Kaufmann, S. H. 2010. The quest for biomarkers in tuberculosis. Drug Discov Today. 15(3-4), 148--57.Google ScholarCross Ref
- Pascual, V. et al. 2010. A genomic approach to human autoimmune diseases. Annu Rev Immunol. 28, 535--71.Google ScholarCross Ref
- Poland, G. A. et al. 2013. Vaccinomics, adversomics, and the immune response network theory: Individualized vaccinology in the 21st century. Semin Immunol. 13, 00023--7.Google Scholar
- Polyak, K., Weinberg, R. A. 2009. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 9(4), 265--73.Google ScholarCross Ref
- Prescott, S. L. et al, 2003. The value of perinatal immune responses in predicting allergic disease at 6 years of age. Allergy. 58(11):1187--94.Google ScholarCross Ref
- Price JV et al. 2013. Characterization of influenza vaccine immunogenicity using influenza antigen microarrays. PLoS One. 8(5), e64555.Google ScholarCross Ref
- Prince, H. E. 2005. Biomarkers for diagnosing and monitoring autoimmune diseases. Biomarkers. 10(Suppl 1), S44--9.Google ScholarCross Ref
- Puck, J. M. 2012. Laboratory technology for population-based screening for severe combined immunodeficiency in neonates, the winner is T-cell receptor excision circles. J Allergy Clin Immunol. 129(3), 607--16.Google ScholarCross Ref
- Robinson, J. et al. 2013. The IMGT/HLA database. Nucleic Acids Res. 41(Database issue), D1222--7.Google Scholar
- Sadun, R. E. et al. 2007. Immune signatures of murine and human cancers reveal unique mechanisms of tumor escape and new targets for cancer immunotherapy. Clin Cancer Res. 13(13), 4016--25.Google ScholarCross Ref
- Saeys, Y., Inza, I., and Larrañaga, P. 2007. A review of feature selection techniques in bioinformatics. Bioinformatics. 23(19), 2507--17. Google ScholarDigital Library
- Sawyers, C. L. 2008. The cancer biomarker problem. Nature. 452(7187), 548--52.Google ScholarCross Ref
- Schetter, A. J. et al. Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways. Carcinogenesis. 31, 37--49.Google Scholar
- Seib KL et al. 2012. Developing vaccines in the era of genomics, a decade of reverse vaccinology. Clin Microbiol Infect. 18(Suppl 5), 109--16.Google ScholarCross Ref
- Shi, Y. et al. 2009. Sparse discriminant analysis for breast cancer biomarker identification and classification. Progress Natural Sci. 19(11), 1635--41.Google ScholarCross Ref
- Sicherer, S. H. and Sampson, H. A. 2009. Food allergy: recent advances in pathophysiology and treatment. Annu Rev Med. 60:261--77.Google ScholarCross Ref
- Smyth, G. K. 2004. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 3.Google Scholar
- Snijders, C. C. P., Matzat, U., and Reips, U. D. 2012. Big data: big gaps of knowledge in the field of Internet Science. Int J Internet Sci. 7(1), 1--5.Google Scholar
- Suarez-Alvarez B., Rodriguez, R. M., Fraga, M. F., López-Larrea, C. 2012. DNA methylation: a promising landscape for immune system-related diseases. Trends Genet. 28(10), 506--14.Google ScholarCross Ref
- Thomas, D. A. and Massagué, J. 2005. TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell. 8(5), 369--80.Google ScholarCross Ref
- Tusher, V. G. et al. 2001. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA. 98, 5116--5121.Google ScholarCross Ref
- Vaughn, H. A. et al. 2004. The humoral immune response to head and neck cancer antigens as defined by the serological analysis of tumor antigens by recombinant cDNA expression cloning. Cancer Immunity 4, 5.Google Scholar
- Vigneron, N., Stroobant, V., Van den Eynde, B. J., and van der Bruggen, P. 2013. Database of T cell-defined human tumor antigens: the 2013 update. Cancer Immun. 13, 15Google Scholar
- Wang, T. et al. 2004. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med. 10(1), 48--54.Google ScholarCross Ref
- Wu, Z. 2009. A review of statistical methods for preprocessing oligonucleotide microarrays. Stat Methods Med Res. 18(6), 533--41.Google ScholarCross Ref
- Xu, Q. W. et al. 2012. An integrated genome-wide approach to discover tumor-specific antigens as potential immunologic and clinical targets in cancer. Cancer Res. 72(24), 6351--61.Google ScholarCross Ref
- Yan, S. D. et al. 1997. Amyloid-β peptide-receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor, a proinflammatory pathway in Alzheimer disease. Proc Natl Acad Sci USA. 94, 5296--301.Google ScholarCross Ref
- Yang C, He Z, Yu W. 2009. Comparison of public peak detection algorithms for MALDI mass spectrometry data analysis. BMC Bioinformatics. 10, 4.Google ScholarCross Ref
- Yang, I. S. et al. 2008. IDBD, infectious disease biomarker database. Nucleic Acids Res. 36, D455--60.Google ScholarCross Ref
- Yilmaz, M. and Christofori, G. 2009. EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 28(1-2), 15--33.Google ScholarCross Ref
- Yousef M et al. 2009. Classification and biomarker identification using gene network modules and support vector machines. BMC Bioinformatics. 10, 337.Google ScholarCross Ref
- Yu W et al. 2006. Statistical methods in proteomics. In Springer Handbook of Engineering Statistics, Springer London, 623--38.Google Scholar
- Yu, Y. et al. 2005. Prediction of pancreatic cancer by serum biomarkers using surface-enhanced laser desorption/ionization-based decision tree classification. Oncology. 68(1), 79--86.Google ScholarCross Ref
- Yuan, Z. and Ghosh, D. 2008. Combining multiple biomarker models in logistic regression. Biometrics. 64(2), 431--439.Google ScholarCross Ref
- Zabel, M. et al. 2012. Assessing candidate serum biomarkers for Alzheimer's disease, a longitudinal study. J Alzheimers Dis. 30(2), 311--21.Google ScholarCross Ref
- Zea, A. H. et al. 2005. Arginase-producing myeloid suppressor cells in renal cell carcinoma patients, a mechanism of tumor evasion. Cancer Res. 65(8), 3044--8.Google ScholarCross Ref
- Zeger SL and Liang KY. 1992. An overview of methods for the analysis of longitudinal data. Stat Med. 11(14-15), 1825--39.Google ScholarCross Ref
- Zhang J et al. 2008. CSF multianalyte profile distinguishes Alzheimer and Parkinson diseases. Am J Clin Pathol. 129(4), 526--9.Google ScholarCross Ref
- Zhang, G. L., Olsen, L. R., Kudahl, U. J., Chitkushev, L. T., and Brusic, V. 2013. Streamlining the development of immunological knowledge bases. Methods Mol Biol. (in press).Google Scholar
- Zhang, Y. et al. 2012. Systematic analysis of the gene expression in the livers of nonalcoholic steatohepatitis, implications on potential biomarkers and molecular pathological mechanism. PLoS One. 7, e51131.Google ScholarCross Ref
- Zheng, G. and Joo, J. 2010. Statistical tests for biomarker development with applications to genetics data. Encyclopedia of Biopharmaceutical Statistic, 1294--9.Google Scholar
- Zitvogel, L. et al. 2010. Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat Rev Clin Oncol. 8(3):151--60.Google ScholarCross Ref
- Zou, W. 2006. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 6(4), 295--307.Google ScholarCross Ref
Index Terms
- Biomarkers in Immunology: from Concepts to Applications
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