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            Clinical Proteomics: Computational Challenges and Solutions

Fung, Eric T.; Enderwick, Cynthia

doi:10.2144/mar0205

Cited by 102 publications

(103 citation statements)

References 12 publications

(13 reference statements)

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“…Even more spectacular advances in mass spectrometry should be expected, with fur-ther improvements in resolution and detectability. With this in mind, it is not surprising that many scientists have decided to use mass spectrometry either as a diagnostic tool or as a cancer or other disease biomarker discovery platform (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Mass Spectrometrymentioning

confidence: 99%

“…The types of cancers that have been examined include ovarian, prostate, breast, bladder, renal, and others, and the biological fluids analyzed include serum, urine, cerebrospinal fluid, nipple aspirate fluid, etc. The apparent successes with this technology have been recently reviewed by many investigators (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). In general, it has been suggested that this technology can achieve much higher diagnostic sensitivity and specificity (approaching 100%) in comparison to the classical cancer biomarkers (31).…”

Section: Mass Spectrometry As a Cancer Biomarker Discovery And Diagnomentioning

confidence: 99%

“…Much has been published on this technology, and excellent reviews have already been prepared (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). My presentation will be biased toward underlining potential limitations that have not been adequately addressed in the already existing extensive literature.…”

mentioning

confidence: 99%

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Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations

Diamandis¹

2004

Molecular & Cellular Proteomics

188

249

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Serum proteomic profiling, by using surfaced-enhanced laser desorption/ionization-time-of-flight mass spectrometry, is one of the most promising new approaches for cancer diagnostics. Exceptional sensitivities and specificities have been reported for some cancer types such as prostate, ovarian, breast, and bladder cancers. These sensitivities/specificities are far superior to those obtained by using classical cancer biomarkers. In this review, I concentrate more on questions that cast doubt on the results reported and propose experiments to investigate these questions in detail, before the technique is used at the clinic. It is clear that the method needs to be externally and thoroughly validated before clinical implementation is warranted. Molecular & Cellular Proteomics 3:367-378, 2004.Our current efforts to combat cancer are not very successful. Despite the recent spectacular advances in molecular medicine, genomics, proteomics, and translational research, mortality rates for the most prevalent cancers have not been significantly reduced. Some of the best available options to combat cancer include primary prevention, earlier diagnosis, and improved therapeutic interventions. We are now witnessing the development of new drugs against cancer that are based on rational instead of empirical designs. There is hope that some of these drugs will prove to be more effective at the clinic than older generations of medicines. In terms of primary prevention, we do not as yet have at hand any robust strategies, because the mechanisms of cancer initiation and progression are still largely unknown.One of the best strategies to combat cancer now is by early diagnosis and administration of effective treatment (1). Another approach includes close monitoring of the cancer patient after initial treatment (usually surgery) to detect early relapse and then prescribe additional therapy. A third valuable approach would be the stratification of patients into subgroups that respond better to different types of treatment (individualized therapy). Medical imaging and serum or tissue biomarkers are valuable tools for monitoring these patients in order to optimize clinical outcomes.In this review, I will concentrate on mass spectrometry as a diagnostic and cancer biomarker discovery tool. Much has been published on this technology, and excellent reviews have already been prepared (2-12). My presentation will be biased toward underlining potential limitations that have not been adequately addressed in the already existing extensive literature. MASS SPECTROMETRYMass spectrometry has been used as a diagnostic tool in clinical laboratories for many decades. This technology has been coupled with gas chromatography (GC/MS) 1 and has been used with success for the identification and quantification of relatively small molecules (with molecular mass Ͻ1,000 Da). Such molecules could be highly informative in newborn screening programs (13), toxicological and forensic applications (14), for delineating various types of inborn errors of metabolism (15...

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Section: Mass Spectrometrymentioning

confidence: 99%

Section: Mass Spectrometry As a Cancer Biomarker Discovery And Diagnomentioning

confidence: 99%

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Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations

Diamandis¹

2004

Molecular & Cellular Proteomics

188

249

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“…Many different techniques exist such as "Inverse Normalization" [36] or "Logarithmic Normalization" [25]. The most frequently used method is global normalization with respect to the average total ion current (TIC) [12,2]. The TIC is the sum of the area of all peaks in a spectra and as such quite insensitive to noise, because noise is mostly canceled out by the summation.…”

Section: Normalizationmentioning

confidence: 99%

Beating the Noise: New Statistical Methods for Detecting Signals in MALDI-TOF Spectra Below Noise Level

Conrad

Leichtle

Hagehülsmann

et al. 2006

Computational Life Sciences II

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“…The former is a modified version of matrix-assisted laser desorption/ionization-TOF MS (MALDI-TOF MS), in that it utilizes ProteinChip arrays for selective capture of chemically or biochemically distinct proteins from a mixed population (Fung & Enderwick, 2002). The protein arrays in SELDI-TOF MS are available with different types of receptors bound to their surface.…”

Section: Introductionmentioning

confidence: 99%

New approaches to identification of bacterial pathogens by surface enhanced laser desorption/ionization time of flight mass spectrometry in concert with artificial neural networks, with special reference to Neisseria gonorrhoeae

Schmid

Lancashire

Culak

et al. 2005

Journal of Medical Microbiology

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Surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) has been applied in large numbers of oncological studies but the microbiological field has not been extensively explored to date. This paper describes the application of SELDI-TOF MS in concert with a multi-layer perceptron artificial neural network (ANN) with a back propagation algorithm for the identification of Neisseria gonorrhoeae. N. gonorrhoeae, the aetiological agent of gonorrhoea, is the second most common sexually transmitted disease in the UK and USA. Analysis of over 350 strains of N. gonorrhoeae and closely related species by SELDI-TOF MS facilitated the design of an ANN model and revealed 20 ion peak descriptors of positive, negative and secondary nature that were paramount for the identification of the pathogen. The model performed with over 96 % efficiency when based on these 20 ion peak descriptors and exhibited a sensitivity of 95 . 7 % and a specificity of 97 . 1 %, with an area under the curve value of 0 . 996. The technology has the potential to link several ANN models for a comprehensive rapid identification platform for clinically important pathogens.

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ProteinChip ^® Clinical Proteomics: Computational Challenges and Solutions

Cited by 102 publications

References 12 publications

Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations

Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations

Beating the Noise: New Statistical Methods for Detecting Signals in MALDI-TOF Spectra Below Noise Level

New approaches to identification of bacterial pathogens by surface enhanced laser desorption/ionization time of flight mass spectrometry in concert with artificial neural networks, with special reference to Neisseria gonorrhoeae

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ProteinChip ® Clinical Proteomics: Computational Challenges and Solutions

Cited by 102 publications

References 12 publications

Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations

Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations

Beating the Noise: New Statistical Methods for Detecting Signals in MALDI-TOF Spectra Below Noise Level

New approaches to identification of bacterial pathogens by surface enhanced laser desorption/ionization time of flight mass spectrometry in concert with artificial neural networks, with special reference to Neisseria gonorrhoeae

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Product

Resources

About

ProteinChip ^® Clinical Proteomics: Computational Challenges and Solutions