Skip to main content
SpringerLink
Log in

Omics-Based Molecular Target and Biomarker Identification

  • Protocol
  • First Online:
Bioinformatics for Omics Data

Part of the book series: Methods in Molecular Biology ((MIMB,volume 719))

Abstract

Genomic, proteomic, and other omic-based approaches are now broadly used in biomedical research to facilitate the understanding of disease mechanisms and identification of molecular targets and biomarkers for therapeutic and diagnostic development. While the Omics technologies and bioinformatics tools for analyzing Omics data are rapidly advancing, the functional analysis and interpretation of the data remain challenging due to the inherent nature of the generally long workflows of Omics experiments. We adopt a strategy that emphasizes the use of curated knowledge resources coupled with expert-guided examination and interpretation of Omics data for the selection of potential molecular targets. We describe a downstream workflow and procedures for functional analysis that focus on biological pathways, from which molecular targets can be derived and proposed for experimental validation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ransohoff, D.F. (2003). Cancer. Developing molecular biomarkers for cancer Science 299, 1679–80.

    Article  PubMed  CAS  Google Scholar 

  2. Riesterer, O., Milas, L., and Ang, K.K. (2007) Use of molecular biomarkers for predicting the response to radiotherapy with or without chemotherapy J Clin Oncol 25, 4075–83.

    Article  PubMed  CAS  Google Scholar 

  3. Kim, Y.S., Maruvada, P., and Milner, J.A. (2008) Metabolomics in biomarker discovery: future uses for cancer prevention Future Oncol 4, 93–102.

    Article  PubMed  CAS  Google Scholar 

  4. Tainsky, M.A. (2009) Genomic and proteomic biomarkers for cancer: a multitude of opportunities Biochim Biophys Acta 1796, 176–93.

    PubMed  CAS  Google Scholar 

  5. Hanash, S. (2004) Integrated global profiling of cancer Nat Rev Cancer 4, 638–44.

    Article  PubMed  CAS  Google Scholar 

  6. Souchelnytskyi, S. (2005) Proteomics of TGF-beta signaling and its impact on breast cancer Expert Rev Proteomics 2, 925–35.

    Article  PubMed  CAS  Google Scholar 

  7. Walgren, J.L., and Thompson, D.C. (2004) Application of proteomic technologies in the drug development process Toxicol Lett 149, 377–85.

    Article  PubMed  CAS  Google Scholar 

  8. Tugwood, J.D., Hollins, L.E., and Cockerill, M.J. (2003) Genomics and the search for novel biomarkers in toxicology Biomarkers 8, 79–92.

    Article  PubMed  CAS  Google Scholar 

  9. Merrick, B.A., and Bruno, M.E. (2004) Genomic and proteomic profiling for biomarkers and signature profiles of toxicity Curr Opin Mol Ther 6, 600–7.

    PubMed  CAS  Google Scholar 

  10. Sreekumar, A., Poisson, L.M., Rajendiran, T.M., Khan, A.P., Cao, Q., Yu, J., Laxman, B., Mehra, R., Lonigro, R.J., Li, Y., Nyati, M.K., Ahsan, A., Kalyana-Sundaram, S., Han, B., Cao, X., Byun, J., Omenn, G.S., Ghosh, D., Pennathur, S., Alexander, D.C., Berger, A., Shuster, J.R., Wei, J.T., Varambally, S., Beecher, C., and Chinnaiyan, A.M. (2009) Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression Nature 457, 910–4.

    Article  PubMed  CAS  Google Scholar 

  11. Martens, J.W., Margossian, A.L., Schmitt, M., Foekens, J., and Harbeck, N. (2009) DNA methylation as a biomarker in breast cancer Future Oncol 5, 1245–56.

    Article  PubMed  CAS  Google Scholar 

  12. Ruan, K., Fang, X., and Ouyang, G. (2009) MicroRNAs: novel regulators in the hallmarks of human cancer Cancer Lett 285, 116–26.

    Article  PubMed  CAS  Google Scholar 

  13. Brooks, S.A. (2009) Strategies for analysis of the glycosylation of proteins: current status and future perspectives Mol Biotechnol 43, 76–88.

    Article  PubMed  CAS  Google Scholar 

  14. Pang, J., Liu, W.P., Liu, X.P., Li, L.Y., Fang, Y.Q., Sun, Q.P., Liu, S.J., Li, M.T., Su, Z.L., and Gao, X. (2010) Profiling protein markers associated with lymph node metastasis in prostate cancer by DIGE-based proteomics analysis J Proteome Res 9(1), 216–26.

    Article  PubMed  CAS  Google Scholar 

  15. Li, J., Zhao, J., Yu, X., Lange, J., Kuerer, H., Krishnamurthy, S., Schilling, E., Khan, S.A., Sukumar, S., and Chan, D.W. (2005) Identification of biomarkers for breast cancer in nipple aspiration and ductal lavage fluid Clin Cancer Res 11, 8312–20.

    Article  PubMed  CAS  Google Scholar 

  16. Zhou, J., Trock, B., Tsangaris, T.N., Friedman, N.B., Shapiro, D., Brotzman, M., Chan-Li, Y., Chan, D.W., and Li, J. (2010) A unique proteolytic fragment of alpha1-antitrypsin is elevated in ductal fluid of breast cancer patient Breast Cancer Res Treat 123(1), 73–86.

    Article  PubMed  CAS  Google Scholar 

  17. Yamamoto, Y., Kosaka, N., Tanaka, M., Koizumi, F., Kanai, Y., Mizutani, T., Murakami, Y., Kuroda, M., Miyajima, A., Kato, T., and Ochiya, T. (2009) MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma Biomarkers 14, 529–38.

    Article  PubMed  CAS  Google Scholar 

  18. Jones, S., Zhang, X., Parsons, D.W., Lin, J.C., Leary, R.J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., Hong, S.M., Fu, B., Lin, M.T., Calhoun, E.S., Kamiyama, M., Walter, K., Nikolskaya, T., Nikolsky, Y., Hartigan, J., Smith, D.R., Hidalgo, M., Leach, S.D., Klein, A.P., Jaffee, E.M., Goggins, M., Maitra, A., Iacobuzio-Donahue, C., Eshleman, J.R., Kern, S.E., Hruban, R.H., Karchin, R., Papadopoulos, N., Parmigiani, G., Vogelstein, B., Velculescu, V.E., and Kinzler, K.W. (2008) Core signaling pathways in human pancreatic cancers revealed by global genomic analyses Science 321, 1801–6.

    Article  PubMed  CAS  Google Scholar 

  19. Zhu, X., Gerstein, M., and Snyder, M. (2007) Getting connected: analysis and principles of biological networks Genes Dev 21, 1010–24.

    Article  PubMed  CAS  Google Scholar 

  20. Pujana, M.A., Han, J.D., Starita, L.M., Stevens, K.N., Tewari, M., Ahn, J.S., Rennert, G., Moreno, V., Kirchhoff, T., Gold, B., Assmann, V., Elshamy, W.M., Rual, J.F., Levine, D., Rozek, L.S., Gelman, R.S., Gunsalus, K.C., Greenberg, R.A., Sobhian, B., Bertin, N., Venkatesan, K., Ayivi-Guedehoussou, N., Solé, X., Hernández, P., Lázaro, C., Nathanson, K.L., Weber, B.L., Cusick, M.E., Hill, D.E., Offit, K., Livingston, D.M., Gruber, S.B., Parvin, J.D., and Vidal, M. (2007) Network modeling links breast cancer susceptibility and centrosome dysfunction Nat Genet 39, 1338–49.

    Article  PubMed  CAS  Google Scholar 

  21. Xia, K., Xue, H., Dong, D., Zhu, S., Wang, J., Zhang, Q., Hou, L., Chen, H., Tao, R., Huang, Z., Fu, Z., Chen, Y.G., and Han, J.D. (2006) Identification of the proliferation/differentiation switch in the cellular network of multicellular organisms PLoS Comput Biol 2, e145.

    Article  PubMed  Google Scholar 

  22. Bertagnolli, M.M. (2009) The forest and the trees: pathways and proteins as colorectal ­cancer biomarkers J Clin Oncol 27(35), 5866–7.

    Article  PubMed  Google Scholar 

  23. Zhang, D.Y., Ye, F., Gao, L., Liu, X., Zhao, X., Che, Y., Wang, H., Wang, L., Wu, J., Song, D., Liu, W., Xu, H., Jiang, B., Zhang, W., Wang, J., and Lee, P. (2009) Proteomics, pathway array and signaling network-based medicine in cancer Cell Div 4, 20.

    Article  PubMed  Google Scholar 

  24. Ptitsyn, A.A., Weil, M.M., and Thamm, D.H. (2008) Systems biology approach to identification of biomarkers for metastatic progression in cancer BMC Bioinformatics 9 Suppl 9, S8.

    Article  PubMed  Google Scholar 

  25. Ideker, T., and Sharan, R. (2008) Protein networks in disease Genome Res 18, 644–52.

    Article  PubMed  CAS  Google Scholar 

  26. Loscalzo, J., Kohane, I., and Barabasi, A.L. (2007) Human disease classification in the postgenomic era: a complex systems approach to human pathobiology Mol Syst Biol 3, 124.

    Article  PubMed  Google Scholar 

  27. Auffray, C. (2007) Protein subnetwork markers improve prediction of cancer outcome Mol Syst Biol 3, 141

    Article  PubMed  Google Scholar 

  28. Chuang, H.Y., Lee, E., Liu, Y.T., Lee, D., and Ideker, T. (2007) Network-based classification of breast cancer metastasis Mol Syst Biol 3, 140.

    Article  PubMed  Google Scholar 

  29. Wang, E., Lenferink, A., and O’Connor-McCourt, M. (2007) Cancer systems biology: exploring cancer-associated genes on cellular networks Cell Mol Life Sci 64, 1752–62.

    Article  PubMed  CAS  Google Scholar 

  30. Do, J.H., and Choi, D.K. (2008) Clustering approaches to identifying gene expression patterns from DNA microarray data Mol Cells 25, 279–88.

    PubMed  CAS  Google Scholar 

  31. Kerr, G., Ruskin, H.J., Crane, M., and Doolan, P. (2008) Techniques for clustering gene expression data Comput Biol Med 38, 283–93.

    Article  PubMed  CAS  Google Scholar 

  32. Weeraratna, A.T., and Taub, D.D. (2007) Microarray data analysis: an overview of design, methodology, and analysis Methods Mol Biol 377, 1–16.

    Article  PubMed  CAS  Google Scholar 

  33. Handl, J., Knowles, J., and Kell, D.B. (2005) Computational cluster validation in post-genomic data analysis Bioinformatics 21, 3201–12.

    Article  PubMed  CAS  Google Scholar 

  34. Huang, H., Hu, Z.Z., Arighi, C.N., and Wu, C.H. (2007) Integration of bioinformatics resources for functional analysis of gene expression and proteomic data Front Biosci 12, 5071–88.

    Article  PubMed  CAS  Google Scholar 

  35. Galperin, M.Y., and Cochrane, G.R. (2009) Nucleic Acids Research annual Database Issue and the NAR online Molecular Biology Database Collection in 2009 Nucleic Acids Res 37(Database issue), D1–4.

    Article  PubMed  CAS  Google Scholar 

  36. UniProt Consortium. (2009) The Universal Protein Resource (UniProt) 2009 Nucleic Acids Res 37(Database issue), D169–74.

    Article  Google Scholar 

  37. Maglott, D., Ostell, J., Pruitt, K.D., and Tatusova, T. (2005) Entrez Gene: gene-centered information at NCBI Nucleic Acids Res 33(Database issue), D54–8.

    Article  PubMed  CAS  Google Scholar 

  38. Bult, C.J., Kadin, J.A., Richardson, J.E., Blake, J.A., and Eppig, J.T. The Mouse Genome Database Group. (2010) The Mouse Genome Database: enhancements and updates Nucleic Acids Res 38(Database issue), D586–92.

    Article  PubMed  CAS  Google Scholar 

  39. Barrell, D., Dimmer, E., Huntley, R.P., Binns, D., O’Donovan, C., and Apweiler, R. (2009) The GOA database in 2009 – an integrated Gene Ontology Annotation resource Nucleic Acids Res 37(Database issue), D396–403.

    Article  PubMed  CAS  Google Scholar 

  40. Kanehisa, M., Araki, M., Goto, S., Hattori, M., Hirakawa, M., Itoh, M., Katayama, T., Kawashima, S., Okuda, S., Tokimatsu, T., and Yamanishi, Y. (2008) KEGG for linking genomes to life and the environment Nucleic Acids Res. 36(Database issue), D480–4.

    PubMed  CAS  Google Scholar 

  41. Schaefer, C.F., Anthony, K., Krupa, S., Buchoff, J., Day, M., Hannay, T., and Buetow, K.H. (2009) PID: the Pathway Interaction Database Nucleic Acids Res 37(Database issue), D674–9.

    Article  PubMed  CAS  Google Scholar 

  42. Aranda, B., Achuthan, P., Alam-Faruque, Y., Armean, I., Bridge, A., Derow, C., Feuermann, M., Ghanbarian, A.T., Kerrien, S., Khadake, J., Kerssemakers, J., Leroy, C., Menden, M., Michaut, M., Montecchi-Palazzi, L., Neuhauser, S.N., Orchard, S., Perreau, V., Roechert, B., van Eijk, K., and Hermjakob, H. (2010) The IntAct molecular interaction database in 2010 Nucleic Acids Res 38(Database issue), D525–31.

    Article  PubMed  CAS  Google Scholar 

  43. Ceol, A., Chatr Aryamontri, A., Licata, L., Peluso, D., Briganti, L., Perfetto, L., Castagnoli, L., and Cesareni, G. (2010) MINT, the molecular interaction database: 2009 update Nucleic Acids Res 38(Database issue), D532–9.

    Article  PubMed  CAS  Google Scholar 

  44. Apweiler, R., Bairoch, A., Wu, C.H., Barker, W.C., Boeckmann, B., Ferro, S., Gasteiger, E., Huang, H., Lopez, R., Magrane, M., Martin, M.J., Natale, D.A., O’Donovan, C., Redaschi, N., and Yeh, L.S. (2004) UniProt: the Universal Protein knowledgebase Nucleic Acids Res 32, D115–9.

    Article  PubMed  CAS  Google Scholar 

  45. Wu, C.H., Huang, H., Nikolskaya, A., Hu, Z., and Barker, W.C. (2004) The iProClass integrated database for protein functional analysis Comput Biol Chem 28, 87–96.

    Article  PubMed  CAS  Google Scholar 

  46. Huang, da W., Sherman, B.T., Stephens, R., Baseler, M.W., Lane, H.C., and Lempicki, R.A. (2008) DAVID gene ID conversion tool Bioinformation 2, 428–30.

    Google Scholar 

  47. Côté, R.G., Jones, P., Martens, L., Kerrien, S., Reisinger, F., Lin, Q., Leinonen, R., Apweiler, R., and Hermjakob, H. (2007) The Protein Identifier Cross-Referencing (PICR) service: reconciling protein identifiers across multiple source databases BMC Bioinformatics 8, 401.

    Article  PubMed  Google Scholar 

  48. Sherman, B.T., Huang, da W., Tan, Q., Guo, Y., Bour, S., Liu, D., Stephens, R., Baseler, M.W., Lane, H.C., and Lempicki, R.A. (2007) DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis BMC Bioinformatics 8, 426.

    Article  PubMed  Google Scholar 

  49. Al-Shahrour, F., Carbonell, J., Minguez, P., Goetz, S., Conesa, A., Tárraga, J., Medina, I., Alloza, E., Montaner, D., and Dopazo, J. (2008) Babelomics: advanced functional profiling of transcriptomics, proteomics and genomics experiments Nucleic Acids Res 36(Web Server issue), W341–6.

    Article  PubMed  CAS  Google Scholar 

  50. Li, Y., and Agarwal, P. (2009) A pathway-based view of human diseases and disease relationships PLoS One 4, e4346.

    Article  PubMed  Google Scholar 

  51. Ozgür, A., Vu, T., Erkan, G., and Radev, D.R. (2008) Identifying gene-disease associations using centrality on a literature mined gene-interaction network Bioinformatics 24, i277–85.

    Article  PubMed  Google Scholar 

  52. Li, S., Wu, L., and Zhang, Z. (2006) Constructing biological networks through combined literature mining and microarray analysis: a LMMA approach Bioinformatics 22, 2143–50.

    Article  PubMed  CAS  Google Scholar 

  53. Nikitin, A., Egorov, S., Daraselia, N., and Mazo, I. (2003) Pathway studio – the analysis and navigation of molecular networks Bioinformatics 19, 2155–7.

    Article  PubMed  CAS  Google Scholar 

  54. Hu, Z.Z., Huang, H., Cheema, A., Jung, M., Dritschilo, A., and Wu, C.H. (2008) Integrated bioinformatics for radiation-induced pathway analysis from proteomics and microarray data J Proteomics Bioinform 1, 47–60.

    Article  PubMed  CAS  Google Scholar 

  55. Nordlund, P., and Reichard, P. (2006) Ribonucleotide reductases Annu Rev Biochem 75, 681–706.

    Article  PubMed  CAS  Google Scholar 

  56. Hu, Z.Z., Valencia, J.C., Huang, H., Chi, A., Shabanowitz, J., Hearing, V.J., Appella, E., and Wu, C.H. (2007) Comparative bioinformatics analyses and profiling of lysosome-related organelle proteomes Int J Mass Spectrom 259, 147–60.

    Article  PubMed  CAS  Google Scholar 

  57. Wheelock, C.E., Wheelock, A.M., Kawashima, S., Diez, D., Kanehisa, M., van Erk, M., Kleemann, R., Haeggström, J.Z., and Goto, S. (2009 ) Systems biology approaches and pathway tools for investigating cardiovascular disease Mol Biosyst 5, 588–602.

    Article  PubMed  CAS  Google Scholar 

  58. Chi, A., Valencia, J.C., Hu, Z.Z., Watabe, H., Yamaguchi, H., Mangini, N.J., Huang, H., Canfield, V.A., Cheng, K.C., Yang, F., Abe, R., Yamagishi, S., Shabanowitz, J., Hearing, V.J., Wu, C., Appella, E., and Hunt, D.F. (2006) Proteomic and bioinformatic characterization of the biogenesis and ­function of melanosomes J Proteome Res 5, 3135–44.

    Article  PubMed  CAS  Google Scholar 

  59. Hu, Z.Z., Kagan, B., Huang, H., Liu, H., Jordan, V.C., Riegel, A., Wellstein, A., and Wu, C. (2009) Pathway and Network Analysis of E2-Induced Apoptosis in Breast Cancer Cells 100th AACR Conference, Denver, CO, April 18–22, Abstract #3285.

    Google Scholar 

  60. Zhang, Y.W., Jones, T.L., Martin, S.E., Caplen, N.J., and Pommier, Y. (2009) Implication of checkpoint kinase-dependent up-regulation of ribonucleotide reductase R2 in DNA damage response J Biol Chem 284, 18085–95.

    Article  PubMed  CAS  Google Scholar 

  61. Zhou, B., and Yen, Y. (2001) Characterization of the human ribonucleotide reductase M2 subunit gene; genomic structure and promoter analyses Cytogenet Cell Genet 95, 52–59.

    Article  PubMed  CAS  Google Scholar 

  62. Zhou, B., Tsai, P., Ker, R., Tsai, J., Ho, R., Yu, J., Shih, J., and Yen, Y. (1998) Overexpression of transfected human ribonucleotide reductase M2 subunit in human cancer cells enhances their invasive potential Clin Exp Metastasis 16, 43–9.

    Article  PubMed  CAS  Google Scholar 

  63. Ransohoff, D.F. (2009). Promises and limitations of biomarkers Recent Results Cancer Res 181, 55–9.

    Article  PubMed  Google Scholar 

  64. Waters, K.M., Pounds, J.G., and Thrall, B.D. (2006) Data merging for integrated microarray and proteomic analysis Brief Funct Genomic Proteomic 5, 261–72.

    Article  PubMed  CAS  Google Scholar 

  65. Wu, C.H., Apweiler, R., Bairoch, A., Natale, D.A., Barker, W.C., Boeckmann, B., Ferro, S., Gasteiger, E., Huang, H., Lopez, R., Magrane, M., Martin, M.J., Mazumder, R., O’Donovan, C., Redaschi, N., Suzek, B. (2006) The Universal Protein Resource (UniProt): an expanding universe of protein information Nucleic Acids Res 34(Database issue), D187–91.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The work has been supported in part by Federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH), under Contract No. HHSN261200800001E (Z.Z.H.), by NCI grant P01CA074175 (A.D.), by NIH grant U01-HG02712 (C.W.), and by the Department of Defense Breast Cancer Research Program W81XWH-06-10590 Center of Excellence Grant (A.W., A.T.R.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Author information

Authors and Affiliations

  1. Lombardi Cancer Center, Georgetown University, Washington, DC, USA

    Zhang-Zhi Hu, Mira Jung, Anatoly Dritschilo, Anna T. Riegel & Anton Wellstein

  2. Center for Bioinformatics & Computational Biology, University of Delaware, Newark, DE, USA

    Hongzhan Huang & Cathy H. Wu

Authors
  1. Zhang-Zhi Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongzhan Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cathy H. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mira Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anatoly Dritschilo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anna T. Riegel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anton Wellstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhang-Zhi Hu .

Editor information

Editors and Affiliations

  1. emergentec biodevelopment GmbH, Gersthofer Strasse 29-31, Vienna, 1180, Austria

    Bernd Mayer

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Hu, ZZ. et al. (2011). Omics-Based Molecular Target and Biomarker Identification. In: Mayer, B. (eds) Bioinformatics for Omics Data. Methods in Molecular Biology, vol 719. Humana Press. https://doi.org/10.1007/978-1-61779-027-0_26

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-027-0_26

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-026-3

  • Online ISBN: 978-1-61779-027-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation