Most prominent method of protein analysis:
Mass Spectrometry stems from the initial effort which relied on protein separation by 2d gel electrophoresis, followed by mass spectrometric identification. Despite its popularity, it fails to fully cover the diversity of protein within a single sample, and only registers the most abundant protein.
Future Concerns:
In the future, we need to find ways to integrate proteomic with genomic and metabolomic effectively.
The research I am interested in: (Biomarkers for Cancer):
I am interested in the research of proteomics as biomarkers* for cancer. The reason is because, with the early diagnosis of cancer, the survive rate of patient greatly increases.
*A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention
Current state of protein biomarkers
Unfortunately, most pre-existing cancer screening tests utalizing proteomics, lack sensitivity and specificity, even the differentiating between benign and malignant tumors is a challenge. But, the potential of biomarkers is promising and it will eventually trump pre-existing diagnostic methods, in sensitivity, specificity and simplicity.
Challenges Faced:
However it is difficult because there are no specific symptoms of early stage cancer and not much is known about oncogensis* or etiology. The dynamic quality of proteins also makes the task more difficult.
Future and Application of Biomarkers:
Once we understand the proteome pathogenesis, we can diagnose cancer properly – according to what went wrong internally as opposed to where the tumors are found. There are four primary applications of biomarkers - for cancer screening, cancer development, targets in cancer therapy and therapeutic response and prognosis.
What has been done in this area?
Research paper utilized:
*(creation of cancer)
The Research paper entitled: “Contribution of oncoproteomics to cancer biomarker discovery” focuses on the type of cancer and the researches done there, while the other: “Recent Advances in Proteomics and Cancer Biomarker Discovery” focuses on the methods applied in the analysis of proteins.Tables’ depicting what has been done till this date:
Table 1(Refer to Appendix) depicts that the usage of biomarkers for diagnosis is still in its embryonic stage.
Table 2 clearly states all the tumor biomarkers which have been identified by proteomics. Once again, we can see that at this point of time, the biomarkers are unrefined and unreliable and thus are not ready for general clinical practice.
Classification and summary of advantages and disadvantages in analytic approaches can be observed in Table 3
Analytic approaches classified – Qualitative & Quantitative:
Qualitative Analysis:
Analytic approaches are classified into qualitative or quantitative analysis. Qualitative analysis entails the aim to study protein expression and composition changes under varied physiological relevant conditions.
The refinement of qualitative analytic methods is possible with the genome sequence database, query algorithms and up-to-date mass spectrometry instruments.
Quantitative Analysis:
Quantitative proteomics provides quantified information. It aims to identify the differences between samples (e.g. healthy and diseased patients). Compiling the information into a database would allow us to classify patients according to the disease, instead of how we currently classify cancer – by the body parts.
Through this we could potentially unveil molecular mechanisms of cancer. Quantitative proteomics would have succeeded once it can identify proteins from complex biological samples and uncover specific diagnostic patterns from a diversity of sample.
What I would pursue further:
Who I would work with:
If I had the resources, I would definitely dive head-in into research for protein biomarkers through the various approaches. I would love to join Mr W. Daniel Hillis at the USC physical science oncology center to build a model of cancer with proteomics.
Proposed Research / Applications of research:
With this model, we would be able to simulate for a specific treatment for every person, which would eventually guide the patient’s body back to health.
Besides just building a model, I also want to develop better biomarkers for diagnosis and early detection. I hope that the future cancer treatments might be tailored according to the molecular alterations identified in the tumor cells of individual patients.
I wish to be an oncologist and a researcher to utilize the biomarkers for therapeutic response and prognosis, this mix will allow me to gather samples / easily and possibly develop viable treatments. Also I could re-evaluate the current approach to cancer – e.g. the effectiveness of radio-/chemo-therapy.
Additionally, I want to improve proteomics analysis methods by increasing the throughput and sensitivity to allow moment-by-moment snap shots of cellular responses. Currently the Nascent method for gel-free analysis is the best option. Furthermore, I could also develop sophisticated algorithms for automated protein identification with the ability to detect post-translational modifications, once a database is available. Or I could even work to expand the database by delving into population proteomics
- 850 Words -
Appendix:
Table 1:
Table 2:
Table 3
Bibliography/Reference:
Websites:
AMA Science, U.S. Department of Energy Office of Science, Office of Biological and Environmental Research, Human Genome Program, JainPharmaBiotech (n.d.). Proteomics. American Medical Association. Retrieved July 24, 2011, from: http://www.ama-assn.org/ama/pub/physician-resources/medical-science/genetics-molecular-medicine/current-topics/proteomics.page
Budimir Zdravkovic (2011, March). Genomics vs. Proteomics. Technology, Entertainment, Design – Ideas worth spreading. Retrieved July 20, 2011, from http://www.ted.com/conversations/649/genomics_vs_proteomics.html
Danny Hillis (2010, October). Danny Hillis: Understanding cancer through proteomics – TALKS - TED PARTNER SERIES. Technology, Entertainment, Design – Ideas worth spreading. Retrieved July 16, 2011, from http://www.ted.com/talks/danny_hillis_two_frontiers_of_cancer_treatment.html
Dr. Malachi Griffith (n.d.) Research Interests. malachigriffith.org. Retrieved July 15, 2011, from http://www.bcgsc.ca/people/malachig/htdocs/malachigriffith.org/research.htm
Kathryn D. Sheikh, Shefali Khanna, Stephen W. Byers, Albert J. Fornace, Jr., and Amrita K. Cheema (2011, April 22). Small Molecule Metabolite Extraction Strategy for Improving LC/MS Detection of Cancer Cell Metabolome - Journal of Biomolecular Techniques. The National Center for Biotechnology Information. Retrieved July 15 2011, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059537/?tool=pubmed
Logan Everett & Endre Boros (2004). I-A. Background: Genomics vs. Proteomics. Discrete Mathematics & Theorectical Computer Science (DIMACS). Retrieved July 20, 2011, from http://dimax.rutgers.edu/~leverett/page1.html
Mary Chitty (n.d.). Overviews: Genomics & proteomics for Drug discovery & development and Molecular Medicine. Cambridge Healthtech Institute. Retrieved July 20, 2011, from http://www.genomicglossaries.com/content/chaptergenomictext.asp
Wikipedia contributors. (n.d.). Proteomics. Wikipedia. Retrieved January 22, 2011, from http://en.wikipedia.org/wiki/Proteomics
Research Papers:
Gary Guishan Xiao & Robert R. Recker & Hong-Wen DengTwo dimensional gel electrophoresis (2-DE)
Two dimensional liquid chromatography (2-D LC)
Isotope-coded affinity tag (ICAT)
tag
tag
Isobaric tags for relative and absolute quantification (iTRAQ)
Stable isotope labeling with amino acids in cell (SILAC)
culture
- . (2008). Recent Advances in Proteomics and Cancer Biomarker Discovery.William CS Cho. (2 April 2007). Molecular Cancer - Contribution of oncoproteomics to cancer biomarker discovery.
Supporting Research Papers used in the Literature Review:
- Javed Khan. (2003). Genomic & Proteomic Technological Advances in Cancer Research.
- Mike Tyers & Matthias Mann. (13 March 2003). From genomics to proteomics
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