Limits...
the need for review and understanding of SELDI/MALDI mass spectroscopy data prior to analysis.

Grizzle WE, Semmes OJ, Bigbee W, Zhu L, Malik G, Oelschlager DK, Manne B, Manne U - Cancer Inform (2005)

Bottom Line: Also, all current mass spectroscopy systems have relatively low sensitivity compared with immunoassays (e.g., ELISA).Foremost, this low resolution results in difficulties in determining what constitutes a "peak" if a peak matching approach is used in analysis.Finally, the Ciphergen(®) system has some "noise" of the baseline which results from the accumulation of charge in the detector system.

View Article: PubMed Central - PubMed

Affiliation: University of Alabama at Birmingham, Birmingham, AL, USA. grizzle@path.uab.edu

ABSTRACT
Multiple studies have reported that surface enhanced laser desorption/ionization time of flight mass spectroscopy (SELDI-TOF-MS) is useful in the early detection of disease based on the analysis of bodily fluids. Use of any multiplex mass spectroscopy based approach as in the analysis of bodily fluids to detect disease must be analyzed with great care due to the susceptibility of multiplex and mass spectroscopy methods to biases introduced via experimental design, patient samples, and/or methodology. Specific biases include those related to experimental design, patients, samples, protein chips, chip reader and spectral analysis. Contributions to biases based on patients include demographics (e.g., age, race, ethnicity, sex), homeostasis (e.g., fasting, medications, stress, time of sampling), and site of analysis (hospital, clinic, other). Biases in samples include conditions of sampling (type of sample container, time of processing, time to storage), conditions of storage, (time and temperature of storage), and prior sample manipulation (freeze thaw cycles). Also, there are many potential biases in methodology which can be avoided by careful experimental design including ensuring that cases and controls are analyzed randomly. All the above forms of biases affect any system based on analyzing multiple analytes and especially all mass spectroscopy based methods, not just SELDI-TOF-MS. Also, all current mass spectroscopy systems have relatively low sensitivity compared with immunoassays (e.g., ELISA). There are several problems which may be unique to the SELDI-TOF-MS system marketed by Ciphergen(®). Of these, the most important is a relatively low resolution (±0.2%) of the bundled mass spectrometer which may cause problems with analysis of data. Foremost, this low resolution results in difficulties in determining what constitutes a "peak" if a peak matching approach is used in analysis. Also, once peaks are selected, the peaks may represent multiple proteins. In addition, because peaks may vary slightly in location due to instrumental drift, long term identification of the same peaks may prove to be a challenge. Finally, the Ciphergen(®) system has some "noise" of the baseline which results from the accumulation of charge in the detector system. Thus, we must be very aware of the factors that may affect the use of proteomics in the early detection of disease, in determining aggressive subsets of cancers, in risk assessment and in monitoring the effectiveness of novel therapies.

No MeSH data available.


Related in: MedlinePlus

The spectra in Figure 8A (titled “Cancer markers from Serum on IMAC Protein Chips 2000 – 8000 Da”) and 8B (titled “Cancer markers from Serum on IMAC Protein Chips 8000 – 100,000 Da”) demonstrate some of the informative spectral peaks (e.g. peak locations) reported in the literature for the early detection of prostate, breast and head and neck tumors as detected using serum samples on IMAC copper activated protein chips.
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Related In: Results  -  Collection

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f8-cin-01-86: The spectra in Figure 8A (titled “Cancer markers from Serum on IMAC Protein Chips 2000 – 8000 Da”) and 8B (titled “Cancer markers from Serum on IMAC Protein Chips 8000 – 100,000 Da”) demonstrate some of the informative spectral peaks (e.g. peak locations) reported in the literature for the early detection of prostate, breast and head and neck tumors as detected using serum samples on IMAC copper activated protein chips.

Mentions: Diamandis has published several criticisms of the general SELDI approach (Diamandis 2003, 2004). In each of these criticisms Diamandis has argued that for the same type of cancer, different laboratories should be identifying the same peaks. This actually should not be the case and even for prostate cancer the identification of different peaks should be the rule rather than unusual result (Grizzle and Meleth, 2004) because different studies have used different chips which bind different proteins and because 100s of peaks may separate cancer from non-cancer and this plus the algorithms chosen may result in different peaks being selected. Similarly, Diamandis (23,24) and others have argued that SELDI may be identifying peaks that are characteristic of inflammatory aspects of neoplasia or epiphenomena of cancers in general (Malik et al, 2005). This clearly is an important issue not only with SELDI-TOF-MS but also with any current forms of mass spectroscopy which have sensitivities of orders of magnitude less than the sensitivities which are necessary to detect tumor products such as PSA and CA125. Some of the peaks identified to date and their association with a specific cancer are demonstrated in Figures 8 and 9. Of interest is that peaks for various cancers have varied to date; however, based on our argument this may be serendipitous rather than an indication that the peaks are specific for a specific cancer.


the need for review and understanding of SELDI/MALDI mass spectroscopy data prior to analysis.

Grizzle WE, Semmes OJ, Bigbee W, Zhu L, Malik G, Oelschlager DK, Manne B, Manne U - Cancer Inform (2005)

The spectra in Figure 8A (titled “Cancer markers from Serum on IMAC Protein Chips 2000 – 8000 Da”) and 8B (titled “Cancer markers from Serum on IMAC Protein Chips 8000 – 100,000 Da”) demonstrate some of the informative spectral peaks (e.g. peak locations) reported in the literature for the early detection of prostate, breast and head and neck tumors as detected using serum samples on IMAC copper activated protein chips.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2657646&req=5

f8-cin-01-86: The spectra in Figure 8A (titled “Cancer markers from Serum on IMAC Protein Chips 2000 – 8000 Da”) and 8B (titled “Cancer markers from Serum on IMAC Protein Chips 8000 – 100,000 Da”) demonstrate some of the informative spectral peaks (e.g. peak locations) reported in the literature for the early detection of prostate, breast and head and neck tumors as detected using serum samples on IMAC copper activated protein chips.
Mentions: Diamandis has published several criticisms of the general SELDI approach (Diamandis 2003, 2004). In each of these criticisms Diamandis has argued that for the same type of cancer, different laboratories should be identifying the same peaks. This actually should not be the case and even for prostate cancer the identification of different peaks should be the rule rather than unusual result (Grizzle and Meleth, 2004) because different studies have used different chips which bind different proteins and because 100s of peaks may separate cancer from non-cancer and this plus the algorithms chosen may result in different peaks being selected. Similarly, Diamandis (23,24) and others have argued that SELDI may be identifying peaks that are characteristic of inflammatory aspects of neoplasia or epiphenomena of cancers in general (Malik et al, 2005). This clearly is an important issue not only with SELDI-TOF-MS but also with any current forms of mass spectroscopy which have sensitivities of orders of magnitude less than the sensitivities which are necessary to detect tumor products such as PSA and CA125. Some of the peaks identified to date and their association with a specific cancer are demonstrated in Figures 8 and 9. Of interest is that peaks for various cancers have varied to date; however, based on our argument this may be serendipitous rather than an indication that the peaks are specific for a specific cancer.

Bottom Line: Also, all current mass spectroscopy systems have relatively low sensitivity compared with immunoassays (e.g., ELISA).Foremost, this low resolution results in difficulties in determining what constitutes a "peak" if a peak matching approach is used in analysis.Finally, the Ciphergen(®) system has some "noise" of the baseline which results from the accumulation of charge in the detector system.

View Article: PubMed Central - PubMed

Affiliation: University of Alabama at Birmingham, Birmingham, AL, USA. grizzle@path.uab.edu

ABSTRACT
Multiple studies have reported that surface enhanced laser desorption/ionization time of flight mass spectroscopy (SELDI-TOF-MS) is useful in the early detection of disease based on the analysis of bodily fluids. Use of any multiplex mass spectroscopy based approach as in the analysis of bodily fluids to detect disease must be analyzed with great care due to the susceptibility of multiplex and mass spectroscopy methods to biases introduced via experimental design, patient samples, and/or methodology. Specific biases include those related to experimental design, patients, samples, protein chips, chip reader and spectral analysis. Contributions to biases based on patients include demographics (e.g., age, race, ethnicity, sex), homeostasis (e.g., fasting, medications, stress, time of sampling), and site of analysis (hospital, clinic, other). Biases in samples include conditions of sampling (type of sample container, time of processing, time to storage), conditions of storage, (time and temperature of storage), and prior sample manipulation (freeze thaw cycles). Also, there are many potential biases in methodology which can be avoided by careful experimental design including ensuring that cases and controls are analyzed randomly. All the above forms of biases affect any system based on analyzing multiple analytes and especially all mass spectroscopy based methods, not just SELDI-TOF-MS. Also, all current mass spectroscopy systems have relatively low sensitivity compared with immunoassays (e.g., ELISA). There are several problems which may be unique to the SELDI-TOF-MS system marketed by Ciphergen(®). Of these, the most important is a relatively low resolution (±0.2%) of the bundled mass spectrometer which may cause problems with analysis of data. Foremost, this low resolution results in difficulties in determining what constitutes a "peak" if a peak matching approach is used in analysis. Also, once peaks are selected, the peaks may represent multiple proteins. In addition, because peaks may vary slightly in location due to instrumental drift, long term identification of the same peaks may prove to be a challenge. Finally, the Ciphergen(®) system has some "noise" of the baseline which results from the accumulation of charge in the detector system. Thus, we must be very aware of the factors that may affect the use of proteomics in the early detection of disease, in determining aggressive subsets of cancers, in risk assessment and in monitoring the effectiveness of novel therapies.

No MeSH data available.


Related in: MedlinePlus