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Biotech / Medical : Ciphergen Biosystems(CIPH): -- Ignore unavailable to you. Want to Upgrade?


To: Biomaven who wrote (200)2/29/2004 4:38:06 PM
From: tuck  Respond to of 510
 
[Reproducibility of protein profiling update]

I'm rereading the literature to see if I can find examples of the various trained algorithms successfully classifying blind sample sets that are new to them. Anyone finds one, please post. This one is not encouraging.

>>Cancer Research 63, 6971-6983, October 15, 2003]
© 2003 American Association for Cancer Research

Proteomic Profiling of Urinary Proteins in Renal Cancer by Surface Enhanced Laser Desorption Ionization and Neural-Network Analysis
Identification of Key Issues Affecting Potential Clinical Utility1

Mark A. Rogers, Paul Clarke, Jason Noble, Nicholas P. Munro, Alan Paul, Peter J. Selby and Rosamonde E. Banks2
Cancer Research UK Clinical Centre [M. A. R., P. C., N. P. M., P. J. S., R. E. B.] and Department of Urology [A. P.], St. James’s University Hospital, Leeds LS9 7TF, and School of Computing, University of Leeds, Leeds LS2 9JT [J. N.], United Kingdom

Recent advances in proteomic profiling technologies, such as surface enhanced laser desorption ionization mass spectrometry, have allowed preliminary profiling and identification of tumor markers in biological fluids in several cancer types and establishment of clinically useful diagnostic computational models. There are currently no routinely used circulating tumor markers for renal cancer, which is often detected incidentally and is frequently advanced at the time of presentation with over half of patients having local or distant tumor spread. We have investigated the clinical utility of surface enhanced laser desorption ionization profiling of urine samples in conjunction with neural-network analysis to either detect renal cancer or to identify proteins of potential use as markers, using samples from a total of 218 individuals, and examined critical technical factors affecting the potential utility of this approach.

Samples from patients before undergoing nephrectomy for clear cell renal cell carcinoma (RCC; n = 48), normal volunteers (n = 38), and outpatients attending with benign diseases of the urogenital tract (n = 20) were used to successfully train neural-network models based on either presence/absence of peaks or peak intensity values, resulting in sensitivity and specificity values of 98.3–100%. Using an initial "blind" group of samples from 12 patients with RCC, 11 healthy controls, and 9 patients with benign diseases to test the models, sensitivities and specificities of 81.8–83.3% were achieved. The robustness of the approach was subsequently evaluated with a group of 80 samples analyzed "blind" 10 months later, (36 patients with RCC, 31 healthy volunteers, and 13 patients with benign urological conditions). However, sensitivities and specificities declined markedly, ranging from 41.0% to 76.6%. Possible contributing factors including sample stability, changing laser performance, and chip variability were examined, which may be important for the long-term robustness of such approaches, and this study highlights the need for rigorous evaluation of such factors in future studies. <<

And here's a full text freebie that deals with the issue:

biomedcentral.com

Cheers, Tuck



To: Biomaven who wrote (200)3/24/2004 2:40:00 AM
From: tuck  Read Replies (2) | Respond to of 510
 
Poking around in the AACR meeting planner turned up the usual incremental improvements in the multiple biomarker approach to diagnosing disease. One example for cervical cancer:

aacr04.agora.com

Also more use in tracking disease progression. Then there was this, regarding the Plasma Proteome Project . . .

>>The HUPO plasma proteome project pilot phase: Reference specimens, technology platform comparisons, and standardized data analyses

Gilbert S. Omenn, David J. States, Daniel W. Chan, Richard J. Simpson, Henning Hermjakob. University of Michigan, Ann Arbor, MI, Johns Hopkins University, Baltimore, MD, Ludwig Institute, Melbourne, Australia, European Bioinformatics Institute, Cambridge, United Kingdom.

A comprehensive, systematic characterization of circulating proteins in health and disease will greatly facilitate development of biomarkers for prevention, diagnosis, and therapy of cancers and other diseases. The Human Proteome Organization (HUPO) has established the Plasma Proteome Project (PPP), as well as liver, brain, antibody, and protein standards initiatives. The PPP Pilot Phase aims to (1) compare the advantages and limitations of many technology platforms in terms of sensitivity of detection, confidence of identification, ease of operation, and costs; (2) contrast reference specimens of human plasma (EDTA, heparin, citrate-anti-coagulated) and serum prepared specifically for this Project, in terms of numbers of proteins identified and any interferences with the various technology platforms; and (3) create a knowledge base in collaboration with the European Bioinformatics Institute and the HUPO Protein Standards Initiative. There are 47 participating laboratories: 17 academic, 6 federal, and 4 corporate in the U.S., 20 in 13 other countries. These laboratories have requested the U.K. NIBSC citrated lyophilized plasma (41) and/or the Caucasian-American (43), Asian-American (19), African American (19), and Chinese (19) sets of three plasmas + serum from small pools of donors. About half of the laboratories will undertake a multi-parameter protocol for specimen handling (temperature, time, freeze/thaw, use of anti-proteases); 30 are testing depletion or pre-fractionation of abundant proteins. With regard to technology platforms, 31 will run 2D gels, 29 liquid chromatography, 25 immediate digestion to peptides, 32 MALDI, LC/MS, MS/MS, 15 direct MS/seldi, 18 labeled proteins. Extensive cross-matching of protein identifications from different search engines and databases is provided centrally. Numerous special projects will perform cross-laboratory, cross-specimen, and cross-technology analyses, culminating in a "jamboree workshop" in June 2004 and public release of the data and findings. The PPP will have a satellite meeting 23-24 October 2004 before the 3rd HUPO World Congress on Proteomics. Also, planning will be initiated for extensive population cohort studies, the beginning of a long-term proteomic exploitation of serum/plasma biomarkers for cancers and many other diseases. <<

Ciphergen has not released a PR concerning the AACR presentations. Might be a small pop.

Cheers, Tuck