Proteomics:  From Basic Research to Diagnostic Application. A Review of Requirements & Needs

Abstract

For several years proteomics research has been expected to lead to the finding of new markers that will translate into clinical tests applicable to samples such as serum, plasma and urine: so-called in vitro diagnostics (IVDs). Attempts to implement technologies applied in proteomics, in particular protein arrays and surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS), as IVD instruments have initiated constructive discussions on opportunities and challenges inherent in such a translation process also with respect to the use of multi-marker profiling approaches and pattern signatures in IVD. Taking into account the role that IVD plays in health care, we describe IVD requirements and needs. Subject to stringent costs versus benefit analyses, IVD has to provide reliable information about a person's condition, prognosis or risk to suffer a disease, thus supporting decisions on treatment or prevention. It is mandatory to fulfill requirements in routine IVD, including disease prevention, diagnosis, prognosis, and treatment monitoring or follow up among others. To fulfill IVD requirements, it is essential to (1) provide diagnostic tests that allow for definite and reliable diagnosis tied to a decision on interventions (prevention, treatment, or nontreatment), (2) meet stringent performance characteristics for each analyte (in particular test accuracy, including both precision of the measurement and trueness of the measurement), and (3) provide adequate diagnostic accuracy, i.e., diagnostic sensitivity and diagnostic specificity, determined by the desired positive and negative predictive values which depend on disease frequency. The fulfillment of essential IVD requirements is mandatory in the regulated environment of modern diagnostics. Addressing IVD needs at an early stage can support a timely and effective transition of findings and developments into routine diagnosis. IVD needs reflect features that are useful in clinical practice. This helps to generate acceptance and assists the implementation process. On the basis of IVD requirements and needs, we outline potential implications for clinical proteomics focused on applied research activities.

Clinical proteomics: A need to define the field and to begin to set adequate standards

“…In an effort to improve this situation and avoid undesirable developments, we have attempted to outline the principal defining parameters for a clinical proteomics study and highlight potential problems and pitfalls. In the interest of clarity and to stay focused, we chose to abstain from covering several important technical issues, such as the limitations and advantages of the different proteomics platforms or validation of biomarkers in large-scale clinical studies, which have been discussed in several review articles that also carry more detailed consideration of several of the aspects we describe below [1,2].…”

Use of an Immunoaffinity-Mass Spectrometry-based Approach for the Quantification of Protein Biomarkers from Serum Samples of Lung Cancer Patients

“…Progress in genomics and proteomics has led to a large number of potential biomarkers (2)(3)(4). However, the promise of these discoveries requires proper verification and validation in the disease of interest (5). The ELISA has been the established platform for quantification of proteins in sera.…”

Mining whole-sample mass spectrometry proteomics data for biomarkers – An overview

“…Such issues have only recently begun to be addressed in a serious fashion (see eg. [Hu et al, 2005], [Karp et al, 2005], [Wagner et al, 2004], [Vitzthum et al, 2005], [West-Nielsen et al, 2005]). It also seems in some sense wasteful to capture a complete proteomic spectrum containing potentially thousands of components when only a handful of known components will ultimately be used for diagnosis.…”